ANEMIA

Functions of erythrocytes

• Transport of respiratory gases

• Large surface area : volume ratio

• Flexible biconcave disc

• Haemoglobin for exchange of gases

• Capable of glycolysis for the source of energy for cell survival

Erythrocyte disorders• Qualitative

• Haemoglobin defect(Anemia, Thalassaemia, sickle cell anemia etc)

• Membrane & enzyme abnormalities(G6PD, eliptocytosis, stomato-ovalocytosis)

• Quantitative• Increased (polycythemia) inherited / acquired

• Decrease (inherited / acquired hypoplasia)

• Bleeding

Anaemia• Reduction in

circulation haemoglobin

• Nutritional deficiency anaemias– Iron deficiency

– B12 & folate deficiency anaemia

– Protein deficiency anaemia

– Scurvy & other element deficiency

Iron anaemiadeficiency

B12 & folate deficiency

Nutritional deficiency anaemiaclinical application

Angular Cheilosis

Koilonychia

Glossitis

Marrow iron storesPlummer-Vinsonsyndrome

Anaemia; Globin chain defects

• Thalassaemias

– Reduced globin chain synthesis

• Alpha and Beta chain synthesis defects

• Haemoglobinopathies

– Abnormal globin chain synthesis

Sickle cell disease

Thalassaemia

Anaemia; Globin chain defects

X-ray appearance ofThalassaemic patient

Hemoglobin electrophoresisfor the diagnosis of thalassaemai

Anaemia; Membrane and enzyme defects

• Membrane defects– Elliptocytosis

– Hemolysis

– Stomato-ovalocytosis– Without haemolysis

• Red cell enzymopathies• G6PD

– Hemolysis after oxidant stress

• Blood loss

Elliptocytosis

G6PD deficiency

Anaemia; Reduced erythroid bone marrow

• Marrow failure• Marrow infiltration

Trephine biopsy

(Aplastic Anemia)

Marrow infiltration Normal trephine

C.B.C

• Haemoglobin - 15±2.5, 14 ±2.5 - g/dl • PCV - 0.47 ±0.07, 0.42 ±0.05 - l/l (%)

– Haematocrit, effective RBC volume - better

• RBC count - 5.5 ±1, 4.8 ± 1 x1012/l• MCHC - Hb/PCV - 30-36 - g/dl

– Hb synthesis within RBC

• MCH - Hb/RBC - 29.5 ± 2.5 pg/l– Average Hb in RBC

• MCV - PCV/RBC 85 ± 8 - fl

Microcytic Anemia (IDA)

Macrocytic Anemia (Meg.):

ANEMIASymptoms : Pallor Jaundice Fatigue Palpitation Dyspnea Vertigo Peptic ulcer Glossitis Dysphagia etc

Classification of Anemia I. Etiologic Classification 1. Impaired RBC production 2. Excessive destruction 3. Blood loss

II. Morphologic Classification 1. Macrocytic anemia 2. Microcytic hypochromic anemia 3. Normochromic normocytic anemia

III. Kinetic Classification

IV. Physiologic Classification

Impaired RBC Production1. Abnormal bone marrow

1.1 Aplastic anemia 1.2 Myelophthisis : Myelofibrosis, Leukemia, Cancer metastasis

2. Essential factors deficiency

2.1 Deficiency anemia : Fe, Vit. B12, Folic acid, etc 2.2 Anemia in renal disease : Erythropoietin

3. Stimulation factor deficiency

3.1 Anemia in chronic disease 3.2 Anemia in hypopituitarism 3.3 Anemia in hypothyroidism

Excessive Destruction of RBC(cont.)

Hemolytic anemia

1. Intracorpuscular defect

1.1 Membrane : Hereditary spherocytosis

Hereditary ovalocytosis, etc.

1.2 Enzyme : G-6PD deficiency, PK def., etc.

1.3 Hemoglobin : Thalassemia, Hemoglobino- pathies

Excessive Destruction of RBC

2. Extracorpuscular defect

2.1 Mechanical : March hemolytic anemia

MAHA (Microangiopathic HA)

2.2 Chemical/Physical

2.3 Infection : Clostridium tetani

2.4 Antibodies : HTR, SLE

2.5 Hypersplenism

Blood Loss

1. Acute blood loss : Accident, GI bleeding

2. Chronic blood loss : Hypermenorrhea

Parasitic infestation

Macrocytic Anemia MCV > 94 MCHC > 31

1. Megaloblastic dyspoiesis

1.1 Vit. B12 deficiency : Pernicious anemia

1.2 Folic acid deficiency : Nutritional megaloblas-

tic anemia, Sprue, Other malabsorption

1.3 Inborn errors of metabolism : Orotic aciduria, etc.

1.4 Abnormal DNA synthesis : Chemotherapy, Anticonvulsant, Oral contraceptives

Macrocytic Anemia MCV > 94 MCHC > 31

2. Non-Megaloblastic dyspoiesis

2.1 Increased erythropoiesis : Hemolytic anemia response to hemorrhage

2.2 Increased membrane surface area : Hepatic disease, Obstructive jaundice, Post-

splenectomy

2.3 Idiopathic : Hypothyroidism, Hypoplastic and Aplastic anemia

Microcytic Hypochromic Anemia MCV < 80 MCHC < 31

1. Fe deficiency anemia : Chronic blood loss, Inadequate diet, Malabsorption, Increased demand, etc.

2. Abnormal globin synthesis : Thalassemia with or without Hemoglobinopathies

3. Abnormal porphyrin and heme synthesis : Pyridoxine responsive anemia, etc.

4. Other abnormal Fe metabolism :

Normocytic Normochromic Anemia MCV 82 - 92 MCHC > 30

1. Blood loss2. Increased plasma volume : Pregnancy, Overhydration3. Hemolytic anemia : depend on each cause

4. Hypoplastic marrow : Aplastic anemia, RBC aplasia5. Infiltrate BM : Leukemia, Multiple myeloma, Myelofibrosis, etc.6. Abnormal endocrine : Hypothyroidism, Adrenal insufficiency, etc.7. Kidney disease / Liver disease / Cirrhosis

Kinetic Classification of Anemia

1. Insufficient erythropoiesis

Stem cells , Hypoplastic marrow, Infiltrated BM

2. Ineffective erythropoiesis

- Megaloblastic anemia

- Thalassemia

- Sideroblastic anemia

3. Uncompensated hemolytic disease with continued

bleeding

Physiologic Classification of Anemia

1. RPI (Reticulocyte Production Index) < 2

(Ineffective erythropoiesis)

1.1 Hypoproliferative anemia

1.2 Maturation disorder

2. RPI > 3 (Effective erythropoiesis)

2.1 Hemolytic anemia

2.2 Blood loss anemia

Physiologic Classification of Anemia

1. RPI (Reticulocyte Production Index) < 2

(Ineffective erythropoiesis)

1.1 Hypoproliferative anemia

(normocytic normochromic, N/N)

- Hypoplastic anemia - Idiopathic/ Chemical/ Infectious / Drug --> Maturation arrest

- Myelophthisic anemia (Marrow infiltration)

- Refractory anemia (Dysmyelopoietic syndrome)

1.1.1 N/N and normal RDW

a) BM failure

b) Decrease marrow stimulation

- Endocrine disease

- Anemia of chronic disease

- Renal disease

1.1.2 Abnormal RBC morphology & RDW

a) Oval macrocyte :- Refractory dysmyelo- poietic

b) Dacrocytes/ tear drops :- Myelophthisic

Physiologic Class. of Anemia RPI < 2

1.2 Maturation disorder

1.2.1 Microcytic, high RDW a) Siderblastic (Microcytic dimorphic RBC) b) Fe def. (Microcytic hypochromic RBC)

1.2.2 Microcytic, normal RDW a) Heterozygous, thalassemia syndrome

b) Anemia of chronic disease

1.2.3 Macrocytic a) Liver disease b) Folate def. c) Vit. B12 def. d) Hemolytic anemia (Normocyte

polychromasia)

Physiologic Class. of Anemia RPI < 2

Physiologic Classification of Anemia

2. RPI > 3

(Effective erythropoiesis)

2.1 Hemolytic anemia

- Intrinsic hereditary disorder - Extrinsic acquired disorder

2.2 Blood loss

- Acute blood loss

- Chronic blood loss (without treatment --> micro-

cytic, hypochromic anemia)

Evaluation of AnemiaA. Hematologic

1. Hematocrit (VPRC preferred)

2. Hemoglobin concentration

3. RBC indices : MCV, MCH, MCHC

4. Leukocyte count

5. Reticulocyte count

6. Platelet count

7. ESR (Erythrocyte sedimentation rate)

8. Stained blood smear : RBC morphology

Evaluation of AnemiaB. Urine analysis

1. Appearance : Color, pH, Clarity, sp gr 2. Test for protein, Bence Jones protein 3. Bilirubin, Uribilinogen 4. Occult blood 5. Microscopic examination

C. Stool

1. Appearance : Color, consistency 2. Occult blood 3. Examination for ova, parasites

Evaluation of AnemiaD. Serum or Plasma

1. BUN 2. Creatinine, if urea N is abnormal 3. Bilirubin : Direct, indirect 4. Protein 5. SI (Serum iron), TIBC (Total iron binding capacity)

E. Special tests in hematology Hb typing / Ham acid test / Coombs’ test, G-6PD,

Ferritin, Sucrose test, Autohemolysis test, Haptoglobin, etc.