53
Prof . Soumaya E Hadhoud Dr .M Kashif Ishaqi Department of Pediatrics TAIBAH UNIVERSITY

Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

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Page 1: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Prof Soumaya E Hadhoud

Dr M Kashif Ishaqi

Department of Pediatrics

TAIBAH UNIVERSITY

To demonstrate knowledge of the process and stages of Haematopoiesis

To demonstrate basic knowledge of the structure and function of Haematopoietic cells

To be able to interpret Normal blood counts

To demonstrate basic knowledge of pathophysiology clinical features and treatment outline of common diseases affecting blood cells

To be able to identify the Normal and abnormal blood cells

Plasma-liquid

55

Blood Cells-Formed elements

45

Three types

1-ErythrocytesRBCs

2-LeukocytesWBCsGranulocytes

Neutrophils

Eosinophils

Basophils

Agranulocytes

Lymphocytes

Monocytes

3-ThrombocytesPlatelets 3

What is Hematopoiesis

Hematopoiesis is a term describing the formation and development of blood cells

Cells of the blood are constantly being lost or destroyed Thus to maintain homeostasis the system must have the capacity for self renewal This system involves

Proliferation of progeny stem cells

Differentiation and maturation of the stem cells into the functional cellular elements

In the adult all blood cell formation (red blood cells white blood cells and platelets) occurs in the Red Bone Marrow or myeloid tissue

Hemocytoblasts (hematopoietic stem cells)

All blood cells arise from hematopoietic stemcell (HSC)

Hormones and growth factors push the cell toward a specific pathway of blood cell development

Hematopoiesis begins as early as the nineteenth day after fertilization in the yolk sac of the embryo

Only erythrocytes are made

The RBCs contain unique fetal hemoglobins

At about 6 weeks of gestation yolk sac production of erythrocytes decreases and production of RBCs in the human embryo itself begins

At two months the fetal liver becomes the chief site of blood cell production

Erythrocytes are produced

The beginnings of leukocyte and thrombocyte production occurs

The spleen kidney thymus and lymph nodes serve as minor sites of blood cell production

The lymph nodes will continue as an important site of lymphopoiesis (production of lymphocytes) throughout life but blood production in the other areas decreases and finally ceases as the bone marrow becomes the primary site of hematopoiesis at about 6 months of gestation and continues throughout life

When the bone marrow becomes the chief site of hematopoiesis leukocyte and thrombocyte production become more prominent

At birth liver and spleen stop hematopoietic activity

Bone marrow now becomes active site of hematopoiesis

Children up to teen years has hematopoiesis in all bones

Hematopoiesis gradually decreases in shafts of long bones

bull In adults red bone marrow is primarily found in bones of the

ndash Axial skeleton

ndash Pelvic and pectoral girdles

ndash Proximal epiphyses of the humerus and femur

Medullary

Hematopoiesis in the bone marrow is called medullary hematopoiesis

Extra medullary

Blood cell production in hematopoietic tissue other than bone marrow

Liver

Spleen

Compensatory mechanism to provide blood cells in times of need

This can lead to hepatomegaly andor splenomegaly (increase in size of the liver andor spleen because of increased functions in the organs)

bull Red blood cells ndashbull carry oxygen via hemoglobin

bull LeukocytesWhite Blood Cellsmake up the cells of the immune system

ndashbull These cells help clear parasites bacteria tumors debris-----

ThrombocytesPlateletsndashbullMust be present for clotting to occur

ndashbull Involved in hemostasis

Red Blood Cell (RBC) synthesis is known as Erythropoiesis

bull In erythropoiesis the hemocytoblast goes through a series of morphological changes culminating in the formation of a cell full of hemoglobin

Sizehellip Same size as the nucleus of a small lymphocyte that is 72 um

Cell shape round

Cytoplasm Pink

Center pallor Hemoglobin is comparatively less in the center showing central pallor on dried film13 size of the cell

Normal RBC suspended in fluid is biconcave

Transport oxygen from lungs to tissues and carbon dioxide from tissues to lungs

72

mm

The appearance of normal circulating blood is relatively uniform with little variation in size and shape Red blood cells will have an area of paleness in the center which is approximately one-third the diameter of the cell

Composed of hemoglobin

Erythropoiesis= RBC production

Stimulated by hypoxia

Controlled by erythropoietin

Hormone synthesized in kidney

Hemolysis= destruction of RBCs

Releases bilirubin into blood stream

Normal lifespan of RBC = 120 days

O

2

O

2

O

2

O

2

oxyhaemoglobin

19-18

Protect body against microorganisms and remove dead cells and debris

MovementsAmeboid

Diapedesis

Chemotaxis

Passive Immunity

Active Immunity

Antigen ndash Antibody

TypesNeutrophils Most common phagocytic cells destroy bacteria (60)

Eosinophils Detoxify chemicals reduce inflammation (4)

Basophils Allergic reactions Release histamine heparin increase inflam response (1)

Lymphocytes Immunity 2 types b amp t Cell types IgG-infection IgM-microbes IgA-Resp amp GI IgE- Allergy IgD-immune response

Monocytes Become macrophages

Basophil Eosinophil

Neutrophil

Lymphocyte

Monocyte

platelet

Cell fragments pinched off from megakaryocytes in red bone marrow

Important in preventing blood loss

Platelet plugs

Promoting formation and contraction of clots

Abnormalities of Haematopoiesis and resulting Blood disorders can affect any of the three main components of blood

Red blood cells which carry oxygen to the bodys tissues

White blood cells which fight infections

Platelets which help blood to clot

Blood disorders affect one or more parts of the blood and prevent your blood from doing its job They can be acute or chronic Many blood disorders are inherited Other causes include other diseases side effects of medicines and a lack of certain nutrients in your diet

Under normal conditions the production release and survival of blood cells is a highly regulated process Quantitative andor qualitative hematologic abnormalities may result when there is an imbalance between cell production release andor survival

Age sex and geographic location are involved in physiologic changes in normal values of the formed cellular elements

Normal values for a group are determined by calculating the mean for healthy individuals of the group and reporting the normal range as the mean +- 2 standard deviations

19-24

The changes caused by disease may be detected by lab tests that measure deviations of the blood constituents from the normal values These lab test may include

Type and cross match

Complete blood count

Red blood count

Hemoglobin measurement

Hematocrit measurement(packed cell volume)

Mean corpuscular volume (MCV)

Mean corpuscular hemoglobin concentration (MCHC)

White blood count

Differential white blood count

Platelet count

Radiologic Studies

CTMRI of lymph tissues

Biopsies

Bone Marrow examination

Lymph node biopsies

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 2: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

To demonstrate knowledge of the process and stages of Haematopoiesis

To demonstrate basic knowledge of the structure and function of Haematopoietic cells

To be able to interpret Normal blood counts

To demonstrate basic knowledge of pathophysiology clinical features and treatment outline of common diseases affecting blood cells

To be able to identify the Normal and abnormal blood cells

Plasma-liquid

55

Blood Cells-Formed elements

45

Three types

1-ErythrocytesRBCs

2-LeukocytesWBCsGranulocytes

Neutrophils

Eosinophils

Basophils

Agranulocytes

Lymphocytes

Monocytes

3-ThrombocytesPlatelets 3

What is Hematopoiesis

Hematopoiesis is a term describing the formation and development of blood cells

Cells of the blood are constantly being lost or destroyed Thus to maintain homeostasis the system must have the capacity for self renewal This system involves

Proliferation of progeny stem cells

Differentiation and maturation of the stem cells into the functional cellular elements

In the adult all blood cell formation (red blood cells white blood cells and platelets) occurs in the Red Bone Marrow or myeloid tissue

Hemocytoblasts (hematopoietic stem cells)

All blood cells arise from hematopoietic stemcell (HSC)

Hormones and growth factors push the cell toward a specific pathway of blood cell development

Hematopoiesis begins as early as the nineteenth day after fertilization in the yolk sac of the embryo

Only erythrocytes are made

The RBCs contain unique fetal hemoglobins

At about 6 weeks of gestation yolk sac production of erythrocytes decreases and production of RBCs in the human embryo itself begins

At two months the fetal liver becomes the chief site of blood cell production

Erythrocytes are produced

The beginnings of leukocyte and thrombocyte production occurs

The spleen kidney thymus and lymph nodes serve as minor sites of blood cell production

The lymph nodes will continue as an important site of lymphopoiesis (production of lymphocytes) throughout life but blood production in the other areas decreases and finally ceases as the bone marrow becomes the primary site of hematopoiesis at about 6 months of gestation and continues throughout life

When the bone marrow becomes the chief site of hematopoiesis leukocyte and thrombocyte production become more prominent

At birth liver and spleen stop hematopoietic activity

Bone marrow now becomes active site of hematopoiesis

Children up to teen years has hematopoiesis in all bones

Hematopoiesis gradually decreases in shafts of long bones

bull In adults red bone marrow is primarily found in bones of the

ndash Axial skeleton

ndash Pelvic and pectoral girdles

ndash Proximal epiphyses of the humerus and femur

Medullary

Hematopoiesis in the bone marrow is called medullary hematopoiesis

Extra medullary

Blood cell production in hematopoietic tissue other than bone marrow

Liver

Spleen

Compensatory mechanism to provide blood cells in times of need

This can lead to hepatomegaly andor splenomegaly (increase in size of the liver andor spleen because of increased functions in the organs)

bull Red blood cells ndashbull carry oxygen via hemoglobin

bull LeukocytesWhite Blood Cellsmake up the cells of the immune system

ndashbull These cells help clear parasites bacteria tumors debris-----

ThrombocytesPlateletsndashbullMust be present for clotting to occur

ndashbull Involved in hemostasis

Red Blood Cell (RBC) synthesis is known as Erythropoiesis

bull In erythropoiesis the hemocytoblast goes through a series of morphological changes culminating in the formation of a cell full of hemoglobin

Sizehellip Same size as the nucleus of a small lymphocyte that is 72 um

Cell shape round

Cytoplasm Pink

Center pallor Hemoglobin is comparatively less in the center showing central pallor on dried film13 size of the cell

Normal RBC suspended in fluid is biconcave

Transport oxygen from lungs to tissues and carbon dioxide from tissues to lungs

72

mm

The appearance of normal circulating blood is relatively uniform with little variation in size and shape Red blood cells will have an area of paleness in the center which is approximately one-third the diameter of the cell

Composed of hemoglobin

Erythropoiesis= RBC production

Stimulated by hypoxia

Controlled by erythropoietin

Hormone synthesized in kidney

Hemolysis= destruction of RBCs

Releases bilirubin into blood stream

Normal lifespan of RBC = 120 days

O

2

O

2

O

2

O

2

oxyhaemoglobin

19-18

Protect body against microorganisms and remove dead cells and debris

MovementsAmeboid

Diapedesis

Chemotaxis

Passive Immunity

Active Immunity

Antigen ndash Antibody

TypesNeutrophils Most common phagocytic cells destroy bacteria (60)

Eosinophils Detoxify chemicals reduce inflammation (4)

Basophils Allergic reactions Release histamine heparin increase inflam response (1)

Lymphocytes Immunity 2 types b amp t Cell types IgG-infection IgM-microbes IgA-Resp amp GI IgE- Allergy IgD-immune response

Monocytes Become macrophages

Basophil Eosinophil

Neutrophil

Lymphocyte

Monocyte

platelet

Cell fragments pinched off from megakaryocytes in red bone marrow

Important in preventing blood loss

Platelet plugs

Promoting formation and contraction of clots

Abnormalities of Haematopoiesis and resulting Blood disorders can affect any of the three main components of blood

Red blood cells which carry oxygen to the bodys tissues

White blood cells which fight infections

Platelets which help blood to clot

Blood disorders affect one or more parts of the blood and prevent your blood from doing its job They can be acute or chronic Many blood disorders are inherited Other causes include other diseases side effects of medicines and a lack of certain nutrients in your diet

Under normal conditions the production release and survival of blood cells is a highly regulated process Quantitative andor qualitative hematologic abnormalities may result when there is an imbalance between cell production release andor survival

Age sex and geographic location are involved in physiologic changes in normal values of the formed cellular elements

Normal values for a group are determined by calculating the mean for healthy individuals of the group and reporting the normal range as the mean +- 2 standard deviations

19-24

The changes caused by disease may be detected by lab tests that measure deviations of the blood constituents from the normal values These lab test may include

Type and cross match

Complete blood count

Red blood count

Hemoglobin measurement

Hematocrit measurement(packed cell volume)

Mean corpuscular volume (MCV)

Mean corpuscular hemoglobin concentration (MCHC)

White blood count

Differential white blood count

Platelet count

Radiologic Studies

CTMRI of lymph tissues

Biopsies

Bone Marrow examination

Lymph node biopsies

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 3: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Plasma-liquid

55

Blood Cells-Formed elements

45

Three types

1-ErythrocytesRBCs

2-LeukocytesWBCsGranulocytes

Neutrophils

Eosinophils

Basophils

Agranulocytes

Lymphocytes

Monocytes

3-ThrombocytesPlatelets 3

What is Hematopoiesis

Hematopoiesis is a term describing the formation and development of blood cells

Cells of the blood are constantly being lost or destroyed Thus to maintain homeostasis the system must have the capacity for self renewal This system involves

Proliferation of progeny stem cells

Differentiation and maturation of the stem cells into the functional cellular elements

In the adult all blood cell formation (red blood cells white blood cells and platelets) occurs in the Red Bone Marrow or myeloid tissue

Hemocytoblasts (hematopoietic stem cells)

All blood cells arise from hematopoietic stemcell (HSC)

Hormones and growth factors push the cell toward a specific pathway of blood cell development

Hematopoiesis begins as early as the nineteenth day after fertilization in the yolk sac of the embryo

Only erythrocytes are made

The RBCs contain unique fetal hemoglobins

At about 6 weeks of gestation yolk sac production of erythrocytes decreases and production of RBCs in the human embryo itself begins

At two months the fetal liver becomes the chief site of blood cell production

Erythrocytes are produced

The beginnings of leukocyte and thrombocyte production occurs

The spleen kidney thymus and lymph nodes serve as minor sites of blood cell production

The lymph nodes will continue as an important site of lymphopoiesis (production of lymphocytes) throughout life but blood production in the other areas decreases and finally ceases as the bone marrow becomes the primary site of hematopoiesis at about 6 months of gestation and continues throughout life

When the bone marrow becomes the chief site of hematopoiesis leukocyte and thrombocyte production become more prominent

At birth liver and spleen stop hematopoietic activity

Bone marrow now becomes active site of hematopoiesis

Children up to teen years has hematopoiesis in all bones

Hematopoiesis gradually decreases in shafts of long bones

bull In adults red bone marrow is primarily found in bones of the

ndash Axial skeleton

ndash Pelvic and pectoral girdles

ndash Proximal epiphyses of the humerus and femur

Medullary

Hematopoiesis in the bone marrow is called medullary hematopoiesis

Extra medullary

Blood cell production in hematopoietic tissue other than bone marrow

Liver

Spleen

Compensatory mechanism to provide blood cells in times of need

This can lead to hepatomegaly andor splenomegaly (increase in size of the liver andor spleen because of increased functions in the organs)

bull Red blood cells ndashbull carry oxygen via hemoglobin

bull LeukocytesWhite Blood Cellsmake up the cells of the immune system

ndashbull These cells help clear parasites bacteria tumors debris-----

ThrombocytesPlateletsndashbullMust be present for clotting to occur

ndashbull Involved in hemostasis

Red Blood Cell (RBC) synthesis is known as Erythropoiesis

bull In erythropoiesis the hemocytoblast goes through a series of morphological changes culminating in the formation of a cell full of hemoglobin

Sizehellip Same size as the nucleus of a small lymphocyte that is 72 um

Cell shape round

Cytoplasm Pink

Center pallor Hemoglobin is comparatively less in the center showing central pallor on dried film13 size of the cell

Normal RBC suspended in fluid is biconcave

Transport oxygen from lungs to tissues and carbon dioxide from tissues to lungs

72

mm

The appearance of normal circulating blood is relatively uniform with little variation in size and shape Red blood cells will have an area of paleness in the center which is approximately one-third the diameter of the cell

Composed of hemoglobin

Erythropoiesis= RBC production

Stimulated by hypoxia

Controlled by erythropoietin

Hormone synthesized in kidney

Hemolysis= destruction of RBCs

Releases bilirubin into blood stream

Normal lifespan of RBC = 120 days

O

2

O

2

O

2

O

2

oxyhaemoglobin

19-18

Protect body against microorganisms and remove dead cells and debris

MovementsAmeboid

Diapedesis

Chemotaxis

Passive Immunity

Active Immunity

Antigen ndash Antibody

TypesNeutrophils Most common phagocytic cells destroy bacteria (60)

Eosinophils Detoxify chemicals reduce inflammation (4)

Basophils Allergic reactions Release histamine heparin increase inflam response (1)

Lymphocytes Immunity 2 types b amp t Cell types IgG-infection IgM-microbes IgA-Resp amp GI IgE- Allergy IgD-immune response

Monocytes Become macrophages

Basophil Eosinophil

Neutrophil

Lymphocyte

Monocyte

platelet

Cell fragments pinched off from megakaryocytes in red bone marrow

Important in preventing blood loss

Platelet plugs

Promoting formation and contraction of clots

Abnormalities of Haematopoiesis and resulting Blood disorders can affect any of the three main components of blood

Red blood cells which carry oxygen to the bodys tissues

White blood cells which fight infections

Platelets which help blood to clot

Blood disorders affect one or more parts of the blood and prevent your blood from doing its job They can be acute or chronic Many blood disorders are inherited Other causes include other diseases side effects of medicines and a lack of certain nutrients in your diet

Under normal conditions the production release and survival of blood cells is a highly regulated process Quantitative andor qualitative hematologic abnormalities may result when there is an imbalance between cell production release andor survival

Age sex and geographic location are involved in physiologic changes in normal values of the formed cellular elements

Normal values for a group are determined by calculating the mean for healthy individuals of the group and reporting the normal range as the mean +- 2 standard deviations

19-24

The changes caused by disease may be detected by lab tests that measure deviations of the blood constituents from the normal values These lab test may include

Type and cross match

Complete blood count

Red blood count

Hemoglobin measurement

Hematocrit measurement(packed cell volume)

Mean corpuscular volume (MCV)

Mean corpuscular hemoglobin concentration (MCHC)

White blood count

Differential white blood count

Platelet count

Radiologic Studies

CTMRI of lymph tissues

Biopsies

Bone Marrow examination

Lymph node biopsies

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 4: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

What is Hematopoiesis

Hematopoiesis is a term describing the formation and development of blood cells

Cells of the blood are constantly being lost or destroyed Thus to maintain homeostasis the system must have the capacity for self renewal This system involves

Proliferation of progeny stem cells

Differentiation and maturation of the stem cells into the functional cellular elements

In the adult all blood cell formation (red blood cells white blood cells and platelets) occurs in the Red Bone Marrow or myeloid tissue

Hemocytoblasts (hematopoietic stem cells)

All blood cells arise from hematopoietic stemcell (HSC)

Hormones and growth factors push the cell toward a specific pathway of blood cell development

Hematopoiesis begins as early as the nineteenth day after fertilization in the yolk sac of the embryo

Only erythrocytes are made

The RBCs contain unique fetal hemoglobins

At about 6 weeks of gestation yolk sac production of erythrocytes decreases and production of RBCs in the human embryo itself begins

At two months the fetal liver becomes the chief site of blood cell production

Erythrocytes are produced

The beginnings of leukocyte and thrombocyte production occurs

The spleen kidney thymus and lymph nodes serve as minor sites of blood cell production

The lymph nodes will continue as an important site of lymphopoiesis (production of lymphocytes) throughout life but blood production in the other areas decreases and finally ceases as the bone marrow becomes the primary site of hematopoiesis at about 6 months of gestation and continues throughout life

When the bone marrow becomes the chief site of hematopoiesis leukocyte and thrombocyte production become more prominent

At birth liver and spleen stop hematopoietic activity

Bone marrow now becomes active site of hematopoiesis

Children up to teen years has hematopoiesis in all bones

Hematopoiesis gradually decreases in shafts of long bones

bull In adults red bone marrow is primarily found in bones of the

ndash Axial skeleton

ndash Pelvic and pectoral girdles

ndash Proximal epiphyses of the humerus and femur

Medullary

Hematopoiesis in the bone marrow is called medullary hematopoiesis

Extra medullary

Blood cell production in hematopoietic tissue other than bone marrow

Liver

Spleen

Compensatory mechanism to provide blood cells in times of need

This can lead to hepatomegaly andor splenomegaly (increase in size of the liver andor spleen because of increased functions in the organs)

bull Red blood cells ndashbull carry oxygen via hemoglobin

bull LeukocytesWhite Blood Cellsmake up the cells of the immune system

ndashbull These cells help clear parasites bacteria tumors debris-----

ThrombocytesPlateletsndashbullMust be present for clotting to occur

ndashbull Involved in hemostasis

Red Blood Cell (RBC) synthesis is known as Erythropoiesis

bull In erythropoiesis the hemocytoblast goes through a series of morphological changes culminating in the formation of a cell full of hemoglobin

Sizehellip Same size as the nucleus of a small lymphocyte that is 72 um

Cell shape round

Cytoplasm Pink

Center pallor Hemoglobin is comparatively less in the center showing central pallor on dried film13 size of the cell

Normal RBC suspended in fluid is biconcave

Transport oxygen from lungs to tissues and carbon dioxide from tissues to lungs

72

mm

The appearance of normal circulating blood is relatively uniform with little variation in size and shape Red blood cells will have an area of paleness in the center which is approximately one-third the diameter of the cell

Composed of hemoglobin

Erythropoiesis= RBC production

Stimulated by hypoxia

Controlled by erythropoietin

Hormone synthesized in kidney

Hemolysis= destruction of RBCs

Releases bilirubin into blood stream

Normal lifespan of RBC = 120 days

O

2

O

2

O

2

O

2

oxyhaemoglobin

19-18

Protect body against microorganisms and remove dead cells and debris

MovementsAmeboid

Diapedesis

Chemotaxis

Passive Immunity

Active Immunity

Antigen ndash Antibody

TypesNeutrophils Most common phagocytic cells destroy bacteria (60)

Eosinophils Detoxify chemicals reduce inflammation (4)

Basophils Allergic reactions Release histamine heparin increase inflam response (1)

Lymphocytes Immunity 2 types b amp t Cell types IgG-infection IgM-microbes IgA-Resp amp GI IgE- Allergy IgD-immune response

Monocytes Become macrophages

Basophil Eosinophil

Neutrophil

Lymphocyte

Monocyte

platelet

Cell fragments pinched off from megakaryocytes in red bone marrow

Important in preventing blood loss

Platelet plugs

Promoting formation and contraction of clots

Abnormalities of Haematopoiesis and resulting Blood disorders can affect any of the three main components of blood

Red blood cells which carry oxygen to the bodys tissues

White blood cells which fight infections

Platelets which help blood to clot

Blood disorders affect one or more parts of the blood and prevent your blood from doing its job They can be acute or chronic Many blood disorders are inherited Other causes include other diseases side effects of medicines and a lack of certain nutrients in your diet

Under normal conditions the production release and survival of blood cells is a highly regulated process Quantitative andor qualitative hematologic abnormalities may result when there is an imbalance between cell production release andor survival

Age sex and geographic location are involved in physiologic changes in normal values of the formed cellular elements

Normal values for a group are determined by calculating the mean for healthy individuals of the group and reporting the normal range as the mean +- 2 standard deviations

19-24

The changes caused by disease may be detected by lab tests that measure deviations of the blood constituents from the normal values These lab test may include

Type and cross match

Complete blood count

Red blood count

Hemoglobin measurement

Hematocrit measurement(packed cell volume)

Mean corpuscular volume (MCV)

Mean corpuscular hemoglobin concentration (MCHC)

White blood count

Differential white blood count

Platelet count

Radiologic Studies

CTMRI of lymph tissues

Biopsies

Bone Marrow examination

Lymph node biopsies

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 5: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Hemocytoblasts (hematopoietic stem cells)

All blood cells arise from hematopoietic stemcell (HSC)

Hormones and growth factors push the cell toward a specific pathway of blood cell development

Hematopoiesis begins as early as the nineteenth day after fertilization in the yolk sac of the embryo

Only erythrocytes are made

The RBCs contain unique fetal hemoglobins

At about 6 weeks of gestation yolk sac production of erythrocytes decreases and production of RBCs in the human embryo itself begins

At two months the fetal liver becomes the chief site of blood cell production

Erythrocytes are produced

The beginnings of leukocyte and thrombocyte production occurs

The spleen kidney thymus and lymph nodes serve as minor sites of blood cell production

The lymph nodes will continue as an important site of lymphopoiesis (production of lymphocytes) throughout life but blood production in the other areas decreases and finally ceases as the bone marrow becomes the primary site of hematopoiesis at about 6 months of gestation and continues throughout life

When the bone marrow becomes the chief site of hematopoiesis leukocyte and thrombocyte production become more prominent

At birth liver and spleen stop hematopoietic activity

Bone marrow now becomes active site of hematopoiesis

Children up to teen years has hematopoiesis in all bones

Hematopoiesis gradually decreases in shafts of long bones

bull In adults red bone marrow is primarily found in bones of the

ndash Axial skeleton

ndash Pelvic and pectoral girdles

ndash Proximal epiphyses of the humerus and femur

Medullary

Hematopoiesis in the bone marrow is called medullary hematopoiesis

Extra medullary

Blood cell production in hematopoietic tissue other than bone marrow

Liver

Spleen

Compensatory mechanism to provide blood cells in times of need

This can lead to hepatomegaly andor splenomegaly (increase in size of the liver andor spleen because of increased functions in the organs)

bull Red blood cells ndashbull carry oxygen via hemoglobin

bull LeukocytesWhite Blood Cellsmake up the cells of the immune system

ndashbull These cells help clear parasites bacteria tumors debris-----

ThrombocytesPlateletsndashbullMust be present for clotting to occur

ndashbull Involved in hemostasis

Red Blood Cell (RBC) synthesis is known as Erythropoiesis

bull In erythropoiesis the hemocytoblast goes through a series of morphological changes culminating in the formation of a cell full of hemoglobin

Sizehellip Same size as the nucleus of a small lymphocyte that is 72 um

Cell shape round

Cytoplasm Pink

Center pallor Hemoglobin is comparatively less in the center showing central pallor on dried film13 size of the cell

Normal RBC suspended in fluid is biconcave

Transport oxygen from lungs to tissues and carbon dioxide from tissues to lungs

72

mm

The appearance of normal circulating blood is relatively uniform with little variation in size and shape Red blood cells will have an area of paleness in the center which is approximately one-third the diameter of the cell

Composed of hemoglobin

Erythropoiesis= RBC production

Stimulated by hypoxia

Controlled by erythropoietin

Hormone synthesized in kidney

Hemolysis= destruction of RBCs

Releases bilirubin into blood stream

Normal lifespan of RBC = 120 days

O

2

O

2

O

2

O

2

oxyhaemoglobin

19-18

Protect body against microorganisms and remove dead cells and debris

MovementsAmeboid

Diapedesis

Chemotaxis

Passive Immunity

Active Immunity

Antigen ndash Antibody

TypesNeutrophils Most common phagocytic cells destroy bacteria (60)

Eosinophils Detoxify chemicals reduce inflammation (4)

Basophils Allergic reactions Release histamine heparin increase inflam response (1)

Lymphocytes Immunity 2 types b amp t Cell types IgG-infection IgM-microbes IgA-Resp amp GI IgE- Allergy IgD-immune response

Monocytes Become macrophages

Basophil Eosinophil

Neutrophil

Lymphocyte

Monocyte

platelet

Cell fragments pinched off from megakaryocytes in red bone marrow

Important in preventing blood loss

Platelet plugs

Promoting formation and contraction of clots

Abnormalities of Haematopoiesis and resulting Blood disorders can affect any of the three main components of blood

Red blood cells which carry oxygen to the bodys tissues

White blood cells which fight infections

Platelets which help blood to clot

Blood disorders affect one or more parts of the blood and prevent your blood from doing its job They can be acute or chronic Many blood disorders are inherited Other causes include other diseases side effects of medicines and a lack of certain nutrients in your diet

Under normal conditions the production release and survival of blood cells is a highly regulated process Quantitative andor qualitative hematologic abnormalities may result when there is an imbalance between cell production release andor survival

Age sex and geographic location are involved in physiologic changes in normal values of the formed cellular elements

Normal values for a group are determined by calculating the mean for healthy individuals of the group and reporting the normal range as the mean +- 2 standard deviations

19-24

The changes caused by disease may be detected by lab tests that measure deviations of the blood constituents from the normal values These lab test may include

Type and cross match

Complete blood count

Red blood count

Hemoglobin measurement

Hematocrit measurement(packed cell volume)

Mean corpuscular volume (MCV)

Mean corpuscular hemoglobin concentration (MCHC)

White blood count

Differential white blood count

Platelet count

Radiologic Studies

CTMRI of lymph tissues

Biopsies

Bone Marrow examination

Lymph node biopsies

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 6: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Hematopoiesis begins as early as the nineteenth day after fertilization in the yolk sac of the embryo

Only erythrocytes are made

The RBCs contain unique fetal hemoglobins

At about 6 weeks of gestation yolk sac production of erythrocytes decreases and production of RBCs in the human embryo itself begins

At two months the fetal liver becomes the chief site of blood cell production

Erythrocytes are produced

The beginnings of leukocyte and thrombocyte production occurs

The spleen kidney thymus and lymph nodes serve as minor sites of blood cell production

The lymph nodes will continue as an important site of lymphopoiesis (production of lymphocytes) throughout life but blood production in the other areas decreases and finally ceases as the bone marrow becomes the primary site of hematopoiesis at about 6 months of gestation and continues throughout life

When the bone marrow becomes the chief site of hematopoiesis leukocyte and thrombocyte production become more prominent

At birth liver and spleen stop hematopoietic activity

Bone marrow now becomes active site of hematopoiesis

Children up to teen years has hematopoiesis in all bones

Hematopoiesis gradually decreases in shafts of long bones

bull In adults red bone marrow is primarily found in bones of the

ndash Axial skeleton

ndash Pelvic and pectoral girdles

ndash Proximal epiphyses of the humerus and femur

Medullary

Hematopoiesis in the bone marrow is called medullary hematopoiesis

Extra medullary

Blood cell production in hematopoietic tissue other than bone marrow

Liver

Spleen

Compensatory mechanism to provide blood cells in times of need

This can lead to hepatomegaly andor splenomegaly (increase in size of the liver andor spleen because of increased functions in the organs)

bull Red blood cells ndashbull carry oxygen via hemoglobin

bull LeukocytesWhite Blood Cellsmake up the cells of the immune system

ndashbull These cells help clear parasites bacteria tumors debris-----

ThrombocytesPlateletsndashbullMust be present for clotting to occur

ndashbull Involved in hemostasis

Red Blood Cell (RBC) synthesis is known as Erythropoiesis

bull In erythropoiesis the hemocytoblast goes through a series of morphological changes culminating in the formation of a cell full of hemoglobin

Sizehellip Same size as the nucleus of a small lymphocyte that is 72 um

Cell shape round

Cytoplasm Pink

Center pallor Hemoglobin is comparatively less in the center showing central pallor on dried film13 size of the cell

Normal RBC suspended in fluid is biconcave

Transport oxygen from lungs to tissues and carbon dioxide from tissues to lungs

72

mm

The appearance of normal circulating blood is relatively uniform with little variation in size and shape Red blood cells will have an area of paleness in the center which is approximately one-third the diameter of the cell

Composed of hemoglobin

Erythropoiesis= RBC production

Stimulated by hypoxia

Controlled by erythropoietin

Hormone synthesized in kidney

Hemolysis= destruction of RBCs

Releases bilirubin into blood stream

Normal lifespan of RBC = 120 days

O

2

O

2

O

2

O

2

oxyhaemoglobin

19-18

Protect body against microorganisms and remove dead cells and debris

MovementsAmeboid

Diapedesis

Chemotaxis

Passive Immunity

Active Immunity

Antigen ndash Antibody

TypesNeutrophils Most common phagocytic cells destroy bacteria (60)

Eosinophils Detoxify chemicals reduce inflammation (4)

Basophils Allergic reactions Release histamine heparin increase inflam response (1)

Lymphocytes Immunity 2 types b amp t Cell types IgG-infection IgM-microbes IgA-Resp amp GI IgE- Allergy IgD-immune response

Monocytes Become macrophages

Basophil Eosinophil

Neutrophil

Lymphocyte

Monocyte

platelet

Cell fragments pinched off from megakaryocytes in red bone marrow

Important in preventing blood loss

Platelet plugs

Promoting formation and contraction of clots

Abnormalities of Haematopoiesis and resulting Blood disorders can affect any of the three main components of blood

Red blood cells which carry oxygen to the bodys tissues

White blood cells which fight infections

Platelets which help blood to clot

Blood disorders affect one or more parts of the blood and prevent your blood from doing its job They can be acute or chronic Many blood disorders are inherited Other causes include other diseases side effects of medicines and a lack of certain nutrients in your diet

Under normal conditions the production release and survival of blood cells is a highly regulated process Quantitative andor qualitative hematologic abnormalities may result when there is an imbalance between cell production release andor survival

Age sex and geographic location are involved in physiologic changes in normal values of the formed cellular elements

Normal values for a group are determined by calculating the mean for healthy individuals of the group and reporting the normal range as the mean +- 2 standard deviations

19-24

The changes caused by disease may be detected by lab tests that measure deviations of the blood constituents from the normal values These lab test may include

Type and cross match

Complete blood count

Red blood count

Hemoglobin measurement

Hematocrit measurement(packed cell volume)

Mean corpuscular volume (MCV)

Mean corpuscular hemoglobin concentration (MCHC)

White blood count

Differential white blood count

Platelet count

Radiologic Studies

CTMRI of lymph tissues

Biopsies

Bone Marrow examination

Lymph node biopsies

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 7: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

At two months the fetal liver becomes the chief site of blood cell production

Erythrocytes are produced

The beginnings of leukocyte and thrombocyte production occurs

The spleen kidney thymus and lymph nodes serve as minor sites of blood cell production

The lymph nodes will continue as an important site of lymphopoiesis (production of lymphocytes) throughout life but blood production in the other areas decreases and finally ceases as the bone marrow becomes the primary site of hematopoiesis at about 6 months of gestation and continues throughout life

When the bone marrow becomes the chief site of hematopoiesis leukocyte and thrombocyte production become more prominent

At birth liver and spleen stop hematopoietic activity

Bone marrow now becomes active site of hematopoiesis

Children up to teen years has hematopoiesis in all bones

Hematopoiesis gradually decreases in shafts of long bones

bull In adults red bone marrow is primarily found in bones of the

ndash Axial skeleton

ndash Pelvic and pectoral girdles

ndash Proximal epiphyses of the humerus and femur

Medullary

Hematopoiesis in the bone marrow is called medullary hematopoiesis

Extra medullary

Blood cell production in hematopoietic tissue other than bone marrow

Liver

Spleen

Compensatory mechanism to provide blood cells in times of need

This can lead to hepatomegaly andor splenomegaly (increase in size of the liver andor spleen because of increased functions in the organs)

bull Red blood cells ndashbull carry oxygen via hemoglobin

bull LeukocytesWhite Blood Cellsmake up the cells of the immune system

ndashbull These cells help clear parasites bacteria tumors debris-----

ThrombocytesPlateletsndashbullMust be present for clotting to occur

ndashbull Involved in hemostasis

Red Blood Cell (RBC) synthesis is known as Erythropoiesis

bull In erythropoiesis the hemocytoblast goes through a series of morphological changes culminating in the formation of a cell full of hemoglobin

Sizehellip Same size as the nucleus of a small lymphocyte that is 72 um

Cell shape round

Cytoplasm Pink

Center pallor Hemoglobin is comparatively less in the center showing central pallor on dried film13 size of the cell

Normal RBC suspended in fluid is biconcave

Transport oxygen from lungs to tissues and carbon dioxide from tissues to lungs

72

mm

The appearance of normal circulating blood is relatively uniform with little variation in size and shape Red blood cells will have an area of paleness in the center which is approximately one-third the diameter of the cell

Composed of hemoglobin

Erythropoiesis= RBC production

Stimulated by hypoxia

Controlled by erythropoietin

Hormone synthesized in kidney

Hemolysis= destruction of RBCs

Releases bilirubin into blood stream

Normal lifespan of RBC = 120 days

O

2

O

2

O

2

O

2

oxyhaemoglobin

19-18

Protect body against microorganisms and remove dead cells and debris

MovementsAmeboid

Diapedesis

Chemotaxis

Passive Immunity

Active Immunity

Antigen ndash Antibody

TypesNeutrophils Most common phagocytic cells destroy bacteria (60)

Eosinophils Detoxify chemicals reduce inflammation (4)

Basophils Allergic reactions Release histamine heparin increase inflam response (1)

Lymphocytes Immunity 2 types b amp t Cell types IgG-infection IgM-microbes IgA-Resp amp GI IgE- Allergy IgD-immune response

Monocytes Become macrophages

Basophil Eosinophil

Neutrophil

Lymphocyte

Monocyte

platelet

Cell fragments pinched off from megakaryocytes in red bone marrow

Important in preventing blood loss

Platelet plugs

Promoting formation and contraction of clots

Abnormalities of Haematopoiesis and resulting Blood disorders can affect any of the three main components of blood

Red blood cells which carry oxygen to the bodys tissues

White blood cells which fight infections

Platelets which help blood to clot

Blood disorders affect one or more parts of the blood and prevent your blood from doing its job They can be acute or chronic Many blood disorders are inherited Other causes include other diseases side effects of medicines and a lack of certain nutrients in your diet

Under normal conditions the production release and survival of blood cells is a highly regulated process Quantitative andor qualitative hematologic abnormalities may result when there is an imbalance between cell production release andor survival

Age sex and geographic location are involved in physiologic changes in normal values of the formed cellular elements

Normal values for a group are determined by calculating the mean for healthy individuals of the group and reporting the normal range as the mean +- 2 standard deviations

19-24

The changes caused by disease may be detected by lab tests that measure deviations of the blood constituents from the normal values These lab test may include

Type and cross match

Complete blood count

Red blood count

Hemoglobin measurement

Hematocrit measurement(packed cell volume)

Mean corpuscular volume (MCV)

Mean corpuscular hemoglobin concentration (MCHC)

White blood count

Differential white blood count

Platelet count

Radiologic Studies

CTMRI of lymph tissues

Biopsies

Bone Marrow examination

Lymph node biopsies

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 8: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

At birth liver and spleen stop hematopoietic activity

Bone marrow now becomes active site of hematopoiesis

Children up to teen years has hematopoiesis in all bones

Hematopoiesis gradually decreases in shafts of long bones

bull In adults red bone marrow is primarily found in bones of the

ndash Axial skeleton

ndash Pelvic and pectoral girdles

ndash Proximal epiphyses of the humerus and femur

Medullary

Hematopoiesis in the bone marrow is called medullary hematopoiesis

Extra medullary

Blood cell production in hematopoietic tissue other than bone marrow

Liver

Spleen

Compensatory mechanism to provide blood cells in times of need

This can lead to hepatomegaly andor splenomegaly (increase in size of the liver andor spleen because of increased functions in the organs)

bull Red blood cells ndashbull carry oxygen via hemoglobin

bull LeukocytesWhite Blood Cellsmake up the cells of the immune system

ndashbull These cells help clear parasites bacteria tumors debris-----

ThrombocytesPlateletsndashbullMust be present for clotting to occur

ndashbull Involved in hemostasis

Red Blood Cell (RBC) synthesis is known as Erythropoiesis

bull In erythropoiesis the hemocytoblast goes through a series of morphological changes culminating in the formation of a cell full of hemoglobin

Sizehellip Same size as the nucleus of a small lymphocyte that is 72 um

Cell shape round

Cytoplasm Pink

Center pallor Hemoglobin is comparatively less in the center showing central pallor on dried film13 size of the cell

Normal RBC suspended in fluid is biconcave

Transport oxygen from lungs to tissues and carbon dioxide from tissues to lungs

72

mm

The appearance of normal circulating blood is relatively uniform with little variation in size and shape Red blood cells will have an area of paleness in the center which is approximately one-third the diameter of the cell

Composed of hemoglobin

Erythropoiesis= RBC production

Stimulated by hypoxia

Controlled by erythropoietin

Hormone synthesized in kidney

Hemolysis= destruction of RBCs

Releases bilirubin into blood stream

Normal lifespan of RBC = 120 days

O

2

O

2

O

2

O

2

oxyhaemoglobin

19-18

Protect body against microorganisms and remove dead cells and debris

MovementsAmeboid

Diapedesis

Chemotaxis

Passive Immunity

Active Immunity

Antigen ndash Antibody

TypesNeutrophils Most common phagocytic cells destroy bacteria (60)

Eosinophils Detoxify chemicals reduce inflammation (4)

Basophils Allergic reactions Release histamine heparin increase inflam response (1)

Lymphocytes Immunity 2 types b amp t Cell types IgG-infection IgM-microbes IgA-Resp amp GI IgE- Allergy IgD-immune response

Monocytes Become macrophages

Basophil Eosinophil

Neutrophil

Lymphocyte

Monocyte

platelet

Cell fragments pinched off from megakaryocytes in red bone marrow

Important in preventing blood loss

Platelet plugs

Promoting formation and contraction of clots

Abnormalities of Haematopoiesis and resulting Blood disorders can affect any of the three main components of blood

Red blood cells which carry oxygen to the bodys tissues

White blood cells which fight infections

Platelets which help blood to clot

Blood disorders affect one or more parts of the blood and prevent your blood from doing its job They can be acute or chronic Many blood disorders are inherited Other causes include other diseases side effects of medicines and a lack of certain nutrients in your diet

Under normal conditions the production release and survival of blood cells is a highly regulated process Quantitative andor qualitative hematologic abnormalities may result when there is an imbalance between cell production release andor survival

Age sex and geographic location are involved in physiologic changes in normal values of the formed cellular elements

Normal values for a group are determined by calculating the mean for healthy individuals of the group and reporting the normal range as the mean +- 2 standard deviations

19-24

The changes caused by disease may be detected by lab tests that measure deviations of the blood constituents from the normal values These lab test may include

Type and cross match

Complete blood count

Red blood count

Hemoglobin measurement

Hematocrit measurement(packed cell volume)

Mean corpuscular volume (MCV)

Mean corpuscular hemoglobin concentration (MCHC)

White blood count

Differential white blood count

Platelet count

Radiologic Studies

CTMRI of lymph tissues

Biopsies

Bone Marrow examination

Lymph node biopsies

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 9: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Medullary

Hematopoiesis in the bone marrow is called medullary hematopoiesis

Extra medullary

Blood cell production in hematopoietic tissue other than bone marrow

Liver

Spleen

Compensatory mechanism to provide blood cells in times of need

This can lead to hepatomegaly andor splenomegaly (increase in size of the liver andor spleen because of increased functions in the organs)

bull Red blood cells ndashbull carry oxygen via hemoglobin

bull LeukocytesWhite Blood Cellsmake up the cells of the immune system

ndashbull These cells help clear parasites bacteria tumors debris-----

ThrombocytesPlateletsndashbullMust be present for clotting to occur

ndashbull Involved in hemostasis

Red Blood Cell (RBC) synthesis is known as Erythropoiesis

bull In erythropoiesis the hemocytoblast goes through a series of morphological changes culminating in the formation of a cell full of hemoglobin

Sizehellip Same size as the nucleus of a small lymphocyte that is 72 um

Cell shape round

Cytoplasm Pink

Center pallor Hemoglobin is comparatively less in the center showing central pallor on dried film13 size of the cell

Normal RBC suspended in fluid is biconcave

Transport oxygen from lungs to tissues and carbon dioxide from tissues to lungs

72

mm

The appearance of normal circulating blood is relatively uniform with little variation in size and shape Red blood cells will have an area of paleness in the center which is approximately one-third the diameter of the cell

Composed of hemoglobin

Erythropoiesis= RBC production

Stimulated by hypoxia

Controlled by erythropoietin

Hormone synthesized in kidney

Hemolysis= destruction of RBCs

Releases bilirubin into blood stream

Normal lifespan of RBC = 120 days

O

2

O

2

O

2

O

2

oxyhaemoglobin

19-18

Protect body against microorganisms and remove dead cells and debris

MovementsAmeboid

Diapedesis

Chemotaxis

Passive Immunity

Active Immunity

Antigen ndash Antibody

TypesNeutrophils Most common phagocytic cells destroy bacteria (60)

Eosinophils Detoxify chemicals reduce inflammation (4)

Basophils Allergic reactions Release histamine heparin increase inflam response (1)

Lymphocytes Immunity 2 types b amp t Cell types IgG-infection IgM-microbes IgA-Resp amp GI IgE- Allergy IgD-immune response

Monocytes Become macrophages

Basophil Eosinophil

Neutrophil

Lymphocyte

Monocyte

platelet

Cell fragments pinched off from megakaryocytes in red bone marrow

Important in preventing blood loss

Platelet plugs

Promoting formation and contraction of clots

Abnormalities of Haematopoiesis and resulting Blood disorders can affect any of the three main components of blood

Red blood cells which carry oxygen to the bodys tissues

White blood cells which fight infections

Platelets which help blood to clot

Blood disorders affect one or more parts of the blood and prevent your blood from doing its job They can be acute or chronic Many blood disorders are inherited Other causes include other diseases side effects of medicines and a lack of certain nutrients in your diet

Under normal conditions the production release and survival of blood cells is a highly regulated process Quantitative andor qualitative hematologic abnormalities may result when there is an imbalance between cell production release andor survival

Age sex and geographic location are involved in physiologic changes in normal values of the formed cellular elements

Normal values for a group are determined by calculating the mean for healthy individuals of the group and reporting the normal range as the mean +- 2 standard deviations

19-24

The changes caused by disease may be detected by lab tests that measure deviations of the blood constituents from the normal values These lab test may include

Type and cross match

Complete blood count

Red blood count

Hemoglobin measurement

Hematocrit measurement(packed cell volume)

Mean corpuscular volume (MCV)

Mean corpuscular hemoglobin concentration (MCHC)

White blood count

Differential white blood count

Platelet count

Radiologic Studies

CTMRI of lymph tissues

Biopsies

Bone Marrow examination

Lymph node biopsies

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 10: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

bull Red blood cells ndashbull carry oxygen via hemoglobin

bull LeukocytesWhite Blood Cellsmake up the cells of the immune system

ndashbull These cells help clear parasites bacteria tumors debris-----

ThrombocytesPlateletsndashbullMust be present for clotting to occur

ndashbull Involved in hemostasis

Red Blood Cell (RBC) synthesis is known as Erythropoiesis

bull In erythropoiesis the hemocytoblast goes through a series of morphological changes culminating in the formation of a cell full of hemoglobin

Sizehellip Same size as the nucleus of a small lymphocyte that is 72 um

Cell shape round

Cytoplasm Pink

Center pallor Hemoglobin is comparatively less in the center showing central pallor on dried film13 size of the cell

Normal RBC suspended in fluid is biconcave

Transport oxygen from lungs to tissues and carbon dioxide from tissues to lungs

72

mm

The appearance of normal circulating blood is relatively uniform with little variation in size and shape Red blood cells will have an area of paleness in the center which is approximately one-third the diameter of the cell

Composed of hemoglobin

Erythropoiesis= RBC production

Stimulated by hypoxia

Controlled by erythropoietin

Hormone synthesized in kidney

Hemolysis= destruction of RBCs

Releases bilirubin into blood stream

Normal lifespan of RBC = 120 days

O

2

O

2

O

2

O

2

oxyhaemoglobin

19-18

Protect body against microorganisms and remove dead cells and debris

MovementsAmeboid

Diapedesis

Chemotaxis

Passive Immunity

Active Immunity

Antigen ndash Antibody

TypesNeutrophils Most common phagocytic cells destroy bacteria (60)

Eosinophils Detoxify chemicals reduce inflammation (4)

Basophils Allergic reactions Release histamine heparin increase inflam response (1)

Lymphocytes Immunity 2 types b amp t Cell types IgG-infection IgM-microbes IgA-Resp amp GI IgE- Allergy IgD-immune response

Monocytes Become macrophages

Basophil Eosinophil

Neutrophil

Lymphocyte

Monocyte

platelet

Cell fragments pinched off from megakaryocytes in red bone marrow

Important in preventing blood loss

Platelet plugs

Promoting formation and contraction of clots

Abnormalities of Haematopoiesis and resulting Blood disorders can affect any of the three main components of blood

Red blood cells which carry oxygen to the bodys tissues

White blood cells which fight infections

Platelets which help blood to clot

Blood disorders affect one or more parts of the blood and prevent your blood from doing its job They can be acute or chronic Many blood disorders are inherited Other causes include other diseases side effects of medicines and a lack of certain nutrients in your diet

Under normal conditions the production release and survival of blood cells is a highly regulated process Quantitative andor qualitative hematologic abnormalities may result when there is an imbalance between cell production release andor survival

Age sex and geographic location are involved in physiologic changes in normal values of the formed cellular elements

Normal values for a group are determined by calculating the mean for healthy individuals of the group and reporting the normal range as the mean +- 2 standard deviations

19-24

The changes caused by disease may be detected by lab tests that measure deviations of the blood constituents from the normal values These lab test may include

Type and cross match

Complete blood count

Red blood count

Hemoglobin measurement

Hematocrit measurement(packed cell volume)

Mean corpuscular volume (MCV)

Mean corpuscular hemoglobin concentration (MCHC)

White blood count

Differential white blood count

Platelet count

Radiologic Studies

CTMRI of lymph tissues

Biopsies

Bone Marrow examination

Lymph node biopsies

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 11: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Red Blood Cell (RBC) synthesis is known as Erythropoiesis

bull In erythropoiesis the hemocytoblast goes through a series of morphological changes culminating in the formation of a cell full of hemoglobin

Sizehellip Same size as the nucleus of a small lymphocyte that is 72 um

Cell shape round

Cytoplasm Pink

Center pallor Hemoglobin is comparatively less in the center showing central pallor on dried film13 size of the cell

Normal RBC suspended in fluid is biconcave

Transport oxygen from lungs to tissues and carbon dioxide from tissues to lungs

72

mm

The appearance of normal circulating blood is relatively uniform with little variation in size and shape Red blood cells will have an area of paleness in the center which is approximately one-third the diameter of the cell

Composed of hemoglobin

Erythropoiesis= RBC production

Stimulated by hypoxia

Controlled by erythropoietin

Hormone synthesized in kidney

Hemolysis= destruction of RBCs

Releases bilirubin into blood stream

Normal lifespan of RBC = 120 days

O

2

O

2

O

2

O

2

oxyhaemoglobin

19-18

Protect body against microorganisms and remove dead cells and debris

MovementsAmeboid

Diapedesis

Chemotaxis

Passive Immunity

Active Immunity

Antigen ndash Antibody

TypesNeutrophils Most common phagocytic cells destroy bacteria (60)

Eosinophils Detoxify chemicals reduce inflammation (4)

Basophils Allergic reactions Release histamine heparin increase inflam response (1)

Lymphocytes Immunity 2 types b amp t Cell types IgG-infection IgM-microbes IgA-Resp amp GI IgE- Allergy IgD-immune response

Monocytes Become macrophages

Basophil Eosinophil

Neutrophil

Lymphocyte

Monocyte

platelet

Cell fragments pinched off from megakaryocytes in red bone marrow

Important in preventing blood loss

Platelet plugs

Promoting formation and contraction of clots

Abnormalities of Haematopoiesis and resulting Blood disorders can affect any of the three main components of blood

Red blood cells which carry oxygen to the bodys tissues

White blood cells which fight infections

Platelets which help blood to clot

Blood disorders affect one or more parts of the blood and prevent your blood from doing its job They can be acute or chronic Many blood disorders are inherited Other causes include other diseases side effects of medicines and a lack of certain nutrients in your diet

Under normal conditions the production release and survival of blood cells is a highly regulated process Quantitative andor qualitative hematologic abnormalities may result when there is an imbalance between cell production release andor survival

Age sex and geographic location are involved in physiologic changes in normal values of the formed cellular elements

Normal values for a group are determined by calculating the mean for healthy individuals of the group and reporting the normal range as the mean +- 2 standard deviations

19-24

The changes caused by disease may be detected by lab tests that measure deviations of the blood constituents from the normal values These lab test may include

Type and cross match

Complete blood count

Red blood count

Hemoglobin measurement

Hematocrit measurement(packed cell volume)

Mean corpuscular volume (MCV)

Mean corpuscular hemoglobin concentration (MCHC)

White blood count

Differential white blood count

Platelet count

Radiologic Studies

CTMRI of lymph tissues

Biopsies

Bone Marrow examination

Lymph node biopsies

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 12: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Sizehellip Same size as the nucleus of a small lymphocyte that is 72 um

Cell shape round

Cytoplasm Pink

Center pallor Hemoglobin is comparatively less in the center showing central pallor on dried film13 size of the cell

Normal RBC suspended in fluid is biconcave

Transport oxygen from lungs to tissues and carbon dioxide from tissues to lungs

72

mm

The appearance of normal circulating blood is relatively uniform with little variation in size and shape Red blood cells will have an area of paleness in the center which is approximately one-third the diameter of the cell

Composed of hemoglobin

Erythropoiesis= RBC production

Stimulated by hypoxia

Controlled by erythropoietin

Hormone synthesized in kidney

Hemolysis= destruction of RBCs

Releases bilirubin into blood stream

Normal lifespan of RBC = 120 days

O

2

O

2

O

2

O

2

oxyhaemoglobin

19-18

Protect body against microorganisms and remove dead cells and debris

MovementsAmeboid

Diapedesis

Chemotaxis

Passive Immunity

Active Immunity

Antigen ndash Antibody

TypesNeutrophils Most common phagocytic cells destroy bacteria (60)

Eosinophils Detoxify chemicals reduce inflammation (4)

Basophils Allergic reactions Release histamine heparin increase inflam response (1)

Lymphocytes Immunity 2 types b amp t Cell types IgG-infection IgM-microbes IgA-Resp amp GI IgE- Allergy IgD-immune response

Monocytes Become macrophages

Basophil Eosinophil

Neutrophil

Lymphocyte

Monocyte

platelet

Cell fragments pinched off from megakaryocytes in red bone marrow

Important in preventing blood loss

Platelet plugs

Promoting formation and contraction of clots

Abnormalities of Haematopoiesis and resulting Blood disorders can affect any of the three main components of blood

Red blood cells which carry oxygen to the bodys tissues

White blood cells which fight infections

Platelets which help blood to clot

Blood disorders affect one or more parts of the blood and prevent your blood from doing its job They can be acute or chronic Many blood disorders are inherited Other causes include other diseases side effects of medicines and a lack of certain nutrients in your diet

Under normal conditions the production release and survival of blood cells is a highly regulated process Quantitative andor qualitative hematologic abnormalities may result when there is an imbalance between cell production release andor survival

Age sex and geographic location are involved in physiologic changes in normal values of the formed cellular elements

Normal values for a group are determined by calculating the mean for healthy individuals of the group and reporting the normal range as the mean +- 2 standard deviations

19-24

The changes caused by disease may be detected by lab tests that measure deviations of the blood constituents from the normal values These lab test may include

Type and cross match

Complete blood count

Red blood count

Hemoglobin measurement

Hematocrit measurement(packed cell volume)

Mean corpuscular volume (MCV)

Mean corpuscular hemoglobin concentration (MCHC)

White blood count

Differential white blood count

Platelet count

Radiologic Studies

CTMRI of lymph tissues

Biopsies

Bone Marrow examination

Lymph node biopsies

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 13: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

The appearance of normal circulating blood is relatively uniform with little variation in size and shape Red blood cells will have an area of paleness in the center which is approximately one-third the diameter of the cell

Composed of hemoglobin

Erythropoiesis= RBC production

Stimulated by hypoxia

Controlled by erythropoietin

Hormone synthesized in kidney

Hemolysis= destruction of RBCs

Releases bilirubin into blood stream

Normal lifespan of RBC = 120 days

O

2

O

2

O

2

O

2

oxyhaemoglobin

19-18

Protect body against microorganisms and remove dead cells and debris

MovementsAmeboid

Diapedesis

Chemotaxis

Passive Immunity

Active Immunity

Antigen ndash Antibody

TypesNeutrophils Most common phagocytic cells destroy bacteria (60)

Eosinophils Detoxify chemicals reduce inflammation (4)

Basophils Allergic reactions Release histamine heparin increase inflam response (1)

Lymphocytes Immunity 2 types b amp t Cell types IgG-infection IgM-microbes IgA-Resp amp GI IgE- Allergy IgD-immune response

Monocytes Become macrophages

Basophil Eosinophil

Neutrophil

Lymphocyte

Monocyte

platelet

Cell fragments pinched off from megakaryocytes in red bone marrow

Important in preventing blood loss

Platelet plugs

Promoting formation and contraction of clots

Abnormalities of Haematopoiesis and resulting Blood disorders can affect any of the three main components of blood

Red blood cells which carry oxygen to the bodys tissues

White blood cells which fight infections

Platelets which help blood to clot

Blood disorders affect one or more parts of the blood and prevent your blood from doing its job They can be acute or chronic Many blood disorders are inherited Other causes include other diseases side effects of medicines and a lack of certain nutrients in your diet

Under normal conditions the production release and survival of blood cells is a highly regulated process Quantitative andor qualitative hematologic abnormalities may result when there is an imbalance between cell production release andor survival

Age sex and geographic location are involved in physiologic changes in normal values of the formed cellular elements

Normal values for a group are determined by calculating the mean for healthy individuals of the group and reporting the normal range as the mean +- 2 standard deviations

19-24

The changes caused by disease may be detected by lab tests that measure deviations of the blood constituents from the normal values These lab test may include

Type and cross match

Complete blood count

Red blood count

Hemoglobin measurement

Hematocrit measurement(packed cell volume)

Mean corpuscular volume (MCV)

Mean corpuscular hemoglobin concentration (MCHC)

White blood count

Differential white blood count

Platelet count

Radiologic Studies

CTMRI of lymph tissues

Biopsies

Bone Marrow examination

Lymph node biopsies

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 14: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Composed of hemoglobin

Erythropoiesis= RBC production

Stimulated by hypoxia

Controlled by erythropoietin

Hormone synthesized in kidney

Hemolysis= destruction of RBCs

Releases bilirubin into blood stream

Normal lifespan of RBC = 120 days

O

2

O

2

O

2

O

2

oxyhaemoglobin

19-18

Protect body against microorganisms and remove dead cells and debris

MovementsAmeboid

Diapedesis

Chemotaxis

Passive Immunity

Active Immunity

Antigen ndash Antibody

TypesNeutrophils Most common phagocytic cells destroy bacteria (60)

Eosinophils Detoxify chemicals reduce inflammation (4)

Basophils Allergic reactions Release histamine heparin increase inflam response (1)

Lymphocytes Immunity 2 types b amp t Cell types IgG-infection IgM-microbes IgA-Resp amp GI IgE- Allergy IgD-immune response

Monocytes Become macrophages

Basophil Eosinophil

Neutrophil

Lymphocyte

Monocyte

platelet

Cell fragments pinched off from megakaryocytes in red bone marrow

Important in preventing blood loss

Platelet plugs

Promoting formation and contraction of clots

Abnormalities of Haematopoiesis and resulting Blood disorders can affect any of the three main components of blood

Red blood cells which carry oxygen to the bodys tissues

White blood cells which fight infections

Platelets which help blood to clot

Blood disorders affect one or more parts of the blood and prevent your blood from doing its job They can be acute or chronic Many blood disorders are inherited Other causes include other diseases side effects of medicines and a lack of certain nutrients in your diet

Under normal conditions the production release and survival of blood cells is a highly regulated process Quantitative andor qualitative hematologic abnormalities may result when there is an imbalance between cell production release andor survival

Age sex and geographic location are involved in physiologic changes in normal values of the formed cellular elements

Normal values for a group are determined by calculating the mean for healthy individuals of the group and reporting the normal range as the mean +- 2 standard deviations

19-24

The changes caused by disease may be detected by lab tests that measure deviations of the blood constituents from the normal values These lab test may include

Type and cross match

Complete blood count

Red blood count

Hemoglobin measurement

Hematocrit measurement(packed cell volume)

Mean corpuscular volume (MCV)

Mean corpuscular hemoglobin concentration (MCHC)

White blood count

Differential white blood count

Platelet count

Radiologic Studies

CTMRI of lymph tissues

Biopsies

Bone Marrow examination

Lymph node biopsies

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 15: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

19-18

Protect body against microorganisms and remove dead cells and debris

MovementsAmeboid

Diapedesis

Chemotaxis

Passive Immunity

Active Immunity

Antigen ndash Antibody

TypesNeutrophils Most common phagocytic cells destroy bacteria (60)

Eosinophils Detoxify chemicals reduce inflammation (4)

Basophils Allergic reactions Release histamine heparin increase inflam response (1)

Lymphocytes Immunity 2 types b amp t Cell types IgG-infection IgM-microbes IgA-Resp amp GI IgE- Allergy IgD-immune response

Monocytes Become macrophages

Basophil Eosinophil

Neutrophil

Lymphocyte

Monocyte

platelet

Cell fragments pinched off from megakaryocytes in red bone marrow

Important in preventing blood loss

Platelet plugs

Promoting formation and contraction of clots

Abnormalities of Haematopoiesis and resulting Blood disorders can affect any of the three main components of blood

Red blood cells which carry oxygen to the bodys tissues

White blood cells which fight infections

Platelets which help blood to clot

Blood disorders affect one or more parts of the blood and prevent your blood from doing its job They can be acute or chronic Many blood disorders are inherited Other causes include other diseases side effects of medicines and a lack of certain nutrients in your diet

Under normal conditions the production release and survival of blood cells is a highly regulated process Quantitative andor qualitative hematologic abnormalities may result when there is an imbalance between cell production release andor survival

Age sex and geographic location are involved in physiologic changes in normal values of the formed cellular elements

Normal values for a group are determined by calculating the mean for healthy individuals of the group and reporting the normal range as the mean +- 2 standard deviations

19-24

The changes caused by disease may be detected by lab tests that measure deviations of the blood constituents from the normal values These lab test may include

Type and cross match

Complete blood count

Red blood count

Hemoglobin measurement

Hematocrit measurement(packed cell volume)

Mean corpuscular volume (MCV)

Mean corpuscular hemoglobin concentration (MCHC)

White blood count

Differential white blood count

Platelet count

Radiologic Studies

CTMRI of lymph tissues

Biopsies

Bone Marrow examination

Lymph node biopsies

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 16: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Basophil Eosinophil

Neutrophil

Lymphocyte

Monocyte

platelet

Cell fragments pinched off from megakaryocytes in red bone marrow

Important in preventing blood loss

Platelet plugs

Promoting formation and contraction of clots

Abnormalities of Haematopoiesis and resulting Blood disorders can affect any of the three main components of blood

Red blood cells which carry oxygen to the bodys tissues

White blood cells which fight infections

Platelets which help blood to clot

Blood disorders affect one or more parts of the blood and prevent your blood from doing its job They can be acute or chronic Many blood disorders are inherited Other causes include other diseases side effects of medicines and a lack of certain nutrients in your diet

Under normal conditions the production release and survival of blood cells is a highly regulated process Quantitative andor qualitative hematologic abnormalities may result when there is an imbalance between cell production release andor survival

Age sex and geographic location are involved in physiologic changes in normal values of the formed cellular elements

Normal values for a group are determined by calculating the mean for healthy individuals of the group and reporting the normal range as the mean +- 2 standard deviations

19-24

The changes caused by disease may be detected by lab tests that measure deviations of the blood constituents from the normal values These lab test may include

Type and cross match

Complete blood count

Red blood count

Hemoglobin measurement

Hematocrit measurement(packed cell volume)

Mean corpuscular volume (MCV)

Mean corpuscular hemoglobin concentration (MCHC)

White blood count

Differential white blood count

Platelet count

Radiologic Studies

CTMRI of lymph tissues

Biopsies

Bone Marrow examination

Lymph node biopsies

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 17: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Cell fragments pinched off from megakaryocytes in red bone marrow

Important in preventing blood loss

Platelet plugs

Promoting formation and contraction of clots

Abnormalities of Haematopoiesis and resulting Blood disorders can affect any of the three main components of blood

Red blood cells which carry oxygen to the bodys tissues

White blood cells which fight infections

Platelets which help blood to clot

Blood disorders affect one or more parts of the blood and prevent your blood from doing its job They can be acute or chronic Many blood disorders are inherited Other causes include other diseases side effects of medicines and a lack of certain nutrients in your diet

Under normal conditions the production release and survival of blood cells is a highly regulated process Quantitative andor qualitative hematologic abnormalities may result when there is an imbalance between cell production release andor survival

Age sex and geographic location are involved in physiologic changes in normal values of the formed cellular elements

Normal values for a group are determined by calculating the mean for healthy individuals of the group and reporting the normal range as the mean +- 2 standard deviations

19-24

The changes caused by disease may be detected by lab tests that measure deviations of the blood constituents from the normal values These lab test may include

Type and cross match

Complete blood count

Red blood count

Hemoglobin measurement

Hematocrit measurement(packed cell volume)

Mean corpuscular volume (MCV)

Mean corpuscular hemoglobin concentration (MCHC)

White blood count

Differential white blood count

Platelet count

Radiologic Studies

CTMRI of lymph tissues

Biopsies

Bone Marrow examination

Lymph node biopsies

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 18: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Abnormalities of Haematopoiesis and resulting Blood disorders can affect any of the three main components of blood

Red blood cells which carry oxygen to the bodys tissues

White blood cells which fight infections

Platelets which help blood to clot

Blood disorders affect one or more parts of the blood and prevent your blood from doing its job They can be acute or chronic Many blood disorders are inherited Other causes include other diseases side effects of medicines and a lack of certain nutrients in your diet

Under normal conditions the production release and survival of blood cells is a highly regulated process Quantitative andor qualitative hematologic abnormalities may result when there is an imbalance between cell production release andor survival

Age sex and geographic location are involved in physiologic changes in normal values of the formed cellular elements

Normal values for a group are determined by calculating the mean for healthy individuals of the group and reporting the normal range as the mean +- 2 standard deviations

19-24

The changes caused by disease may be detected by lab tests that measure deviations of the blood constituents from the normal values These lab test may include

Type and cross match

Complete blood count

Red blood count

Hemoglobin measurement

Hematocrit measurement(packed cell volume)

Mean corpuscular volume (MCV)

Mean corpuscular hemoglobin concentration (MCHC)

White blood count

Differential white blood count

Platelet count

Radiologic Studies

CTMRI of lymph tissues

Biopsies

Bone Marrow examination

Lymph node biopsies

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 19: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Under normal conditions the production release and survival of blood cells is a highly regulated process Quantitative andor qualitative hematologic abnormalities may result when there is an imbalance between cell production release andor survival

Age sex and geographic location are involved in physiologic changes in normal values of the formed cellular elements

Normal values for a group are determined by calculating the mean for healthy individuals of the group and reporting the normal range as the mean +- 2 standard deviations

19-24

The changes caused by disease may be detected by lab tests that measure deviations of the blood constituents from the normal values These lab test may include

Type and cross match

Complete blood count

Red blood count

Hemoglobin measurement

Hematocrit measurement(packed cell volume)

Mean corpuscular volume (MCV)

Mean corpuscular hemoglobin concentration (MCHC)

White blood count

Differential white blood count

Platelet count

Radiologic Studies

CTMRI of lymph tissues

Biopsies

Bone Marrow examination

Lymph node biopsies

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 20: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

19-24

The changes caused by disease may be detected by lab tests that measure deviations of the blood constituents from the normal values These lab test may include

Type and cross match

Complete blood count

Red blood count

Hemoglobin measurement

Hematocrit measurement(packed cell volume)

Mean corpuscular volume (MCV)

Mean corpuscular hemoglobin concentration (MCHC)

White blood count

Differential white blood count

Platelet count

Radiologic Studies

CTMRI of lymph tissues

Biopsies

Bone Marrow examination

Lymph node biopsies

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 21: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Radiologic Studies

CTMRI of lymph tissues

Biopsies

Bone Marrow examination

Lymph node biopsies

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 22: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Common Laboratory Tests for Hematologic and Lymphatic Disorders

19042011 28

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 23: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

19042011 29

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 24: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

RBC

Anemiasndashldquolacking bloodrdquo

Polycythemiandashldquomany blood cellsrdquo

WBC

Leukopeniandashlow white blood cell count

bull Leukemiandashhigh white blood cell count

ndash Acute quickly advancing blast--‐type cells

ndash Chronic slowly advancing more mature cells

Platelets

Thrombocytopenia

Thrombocytosis

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 25: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

ErythrocytesRed Blood Cells

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 26: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Definition of Anaemia

Reduction of haemoglobin concentration or red blood cell (RBC) volume below the range of normal values

Means and ranges of normal haemoglobinvaries with age and sex

Anaemia is not a diagnosis but sign of a disease which should be investigated

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 27: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Normal Mean amp Lower Limits of Normal Hb HCT amp MCV

AGE (YR) HEMOGLOBIN(GDL)

Mean Lower Limit

HEMATOC RIT ()

Mean Lower Limit

MCV (Μm3)

MCV (fL) 70+ Age

(years)

Mean Lower Limit

Newborn 168 140 55 45 119 110

05-19 125 110 37 33 77 70

2-4 125 110 38 34 79 73

5-7 130 115 39 35 81 75

8-11 135 120 40 36 83 76

12-14 female 135 120 41 36 85 78

12-14 male 140 125 43 37 84 77

15-17 female 140 120 41 36 87 79

15-17 male 150 130 46 38 86 78Dr M KASHIF ISHAQI

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 28: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

What happens in anaemia O2 carrying capacity of the blood

Increase cardiac output augmented oxygen extraction and shunting of blood flow towards vital organs and tissues

Increased concentration of 23-diphosphoglycerate within RBC with resultant right shift of the oxygen dissociation curve

Few physiological disturbances occur until Hb lt 80gL

Pallor only evident when Hb lt 80gL

Younger children less symptoms and signs

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 29: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Symptoms amp signs of anaemiaSymptoms

Pallor

Lethargy amp irritability

Decreased exercise tolerance shortness of breath

Dizziness

Signs

Pale mucous membrane amp palmar creases

Tachycardia

Tachypnea

Flow murmur

Cardiac failure (severe anaemia)

Other signs related to underlying disease process

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 30: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

destructionproduction

factory

Pathological classification

Substrate (Ineffective erythropoiesis)

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 31: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Pathological classification

1 Inadequate production of RBC in the bone marrow

RBC precursors in the bone marrow (red cell aplasia)

eg Diamond Blackfan syndrome

Aplastic Anemia

Deficiency of specific factors

eg iron folate B12 deficiency

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 32: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Pathological classification

2 Increased destruction of RBC

Intrinsic abnormalities of RBC

eg hereditary spherocytosis thalassaemia sickle cell anaemia

Immune mediated

eg autoimmune haemolytic anaemia Rhesus or ABO isoimmunization drugs

Dr M KASHIF ISHAQI

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 33: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Dr M KASHIF ISHAQI

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 34: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Anaemia

History

Physical examination

Laboratory Criteria

Age PrematuritySex x-linked eg G-6PD def Diet Iron early cow goat milk vegetarian motherJaundice pallor Dark colored urineGallstonesCholecystectomy TrasfusionSplenectomy chronic illness blood lossDrugs Pica Fava BeanFamily history

Pale Yellow sclera Visceromegaly LymphadenopathySigns of Nutritional deficiencyCongenital malformation

CBC HB WCC

MCV PLT Polys

Peripheral SmearRetics Count

BilirubinUnconjugated LDH Haptoglobin Urine DR

Dr M KASHIF ISHAQI

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 35: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Low Hb=Anemia

MCV

Low

microcytic

Normal

normocytic

High

macrocytic

Measure Ferritin

Low Normalhigh

Iron def

Anemia

Anemia of

chronic disease

Congenital Hb dis

Reticulocyte count

high low Anemia of chronic disease

Renal failure

Marrow failure

Hemolytic anemia or

blood loss

Measure B12 + folate

Low

Megaloblastic

anemia

Normal

Dr M KASHIF ISHAQI

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 36: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Sickle Cell

bull Red cells with pointed endsbull Crescent shapebull No central pallorbull Very dense hemoglobin

Key features

Associated disease

Hemoglobin SS

Hemoglobin SC

Hemoglobin SD

S- beta thalassaemia

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 37: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Thalassaemia

1048697 Thalassemia spectrum of diseases characterized by

reduced or absent production of one or more globin chains

1048697 Disrupts the ratio of alphabeta production

- thalassaemia

Defect in globin chain synthesis

- thalassaemia trait - thalassaemia major

Low MCV

Trait Major

MCV

Hb N or sl

Hb elect HbA2 no A HbF

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 38: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

White blood cellsWBC

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 39: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

Most common malignant neoplasms in childhood (41 of all malignancies in children lt15 yrs of age)

Acute lymphoblastic leukemia (ALL) 77Acute myelogenous leukemia (AML) 11Chronic myelogenous leukemia (CML) 2ndash3Juvenile chronic myelogenous leukemia (JCML) 1ndash2 Chronic lymphoblastic leukemia (CLL) rare

Leukemias a group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells

These cells have a growth advantage over normal cellular elements because of

Proliferate uncontrolledFail to respond to normal growth inhibition mechanismsDo not undergo apoptotic changesInfiltrate normal organs

Leukemia

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 40: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

ALL Clinical Presentations

General Malaise anorexia

Anemia

Neutropenia

Thrombocytopenia

Bone marrow infiltration

Pallor lethargy

Infection

Bruising petechiae nose bleeds

Bone pain

Reticulo-endothelial infiltration

Hepatosplenomegaly

Lymphadenopathy superior mediastinal obsruction

Other organInfitration

CNS

Testes

Headaches vomiting convulsions nerve palsies

Testicular enlargement

Rare at diagnosis more often at relapse

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 41: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

ALL subtypes

Subtypes Descriptions

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 42: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

THROMBOCYTESPLATELETS

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 43: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will

THROMBOCYTOPENIA

DRUG INDUCED

BONE MARROW FAILURE

Viral Infections

Chemotherapy amp Radiation Therapy

Infiltration of Abnormal Cells

Aplastic Anemia

Leukemia

Metastatic Cancer

HYPERSPLENISM

OTHER CAUSESIdiopathic Thrombocytopenia Purpura (ITP)

HIV Virus

Page 44: Prof . SoumayaE Hadhoud Dr .M KashifIshaqi€¦ · production occurs The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production. The lymph nodes will