164
RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related to platelets Hemorrhagic diathesis

RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Embed Size (px)

Citation preview

Page 1: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

RED CELL DISORDERS

Anemia of blood lossHemolytic anemiaAnemia of decreased erythropoiesisPolycythemiaBleeding disordersBleeding disorders related to plateletsHemorrhagic diathesis

Page 2: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

AnemiaIt is defined as reduction in the total

circulating RBC mass below the normal limits.

The red cell mass is measured by1. Hematocrit value.( ratio of packed

red cells to the total blood volume)2.Hemoglobin concentration

Page 3: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Blood LossAcute: trauma

Chronic: lesions of gastrointestinal tract, gynecologic disturbances. The features of chronic blood loss anemia are the same as iron deficiency anemia, and is defined as a situation in which the production cannot keep up with the loss.

Page 4: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Acute blood loss result in Hypovolemic shockThere is normocytic nromochromic anemiaDecreased in hematocritIncreased erythropoisis and reticulocytosisThere is leuckocytosis due to mobilization by

adrenergic hormones in turn due to hypotension compensatory release of adrenergic hormones, thrombocytosis.

Page 5: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

HEMOLYTICHEREDITARY

MEMBRANE disorders: e.g., spherocytosisENZYME disorders: e.g., G6PD deficciencyHGB disorders (hemoglobinopathies)

ACQUIREDMEMBRANE disorders (PNH)ANTIBODY MEDIATED, transfusion or

autoantibodiesMECHANICAL TRAUMAINFECTIONSDRUGS, TOXINSHYPERSPLENISM

Page 6: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

IMPAIRED PRODUCTIONDisturbance of proliferation and differentiation of stem cells:

Aplastic anemias, Pure RBC aplasia, Renal failure

Page 7: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Disturbance of proliferation and maturation of erythroblasts

Defective DNA synthesis: (Megaloblastic Anemia), deficiency of folate and Vitamin B12

Page 8: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Defective heme synthesis: (Fe) Iron deficiency anemia

Deficient globin synthesis: Thalassemias

Page 9: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Increased Destruction (Hemolytic Anemias) Intrinsic (intracorpuscular) abnormalities. 

 Hereditary   Membrane abnormlities       Membrane skeleton proteins: H.Spherocytosis, H.Elliptocytosis     

Page 10: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

 Enzyme deficiencies     Glycolytic enzymes: pyruvate kinase, Hexokinase Enzymes of hexose

monophosphate shunt: glucose-6-phosphate dehydrogenase,

glutathione synthetase

Page 11: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

 Disorders of hemoglobin synthesis Deficient globin synthesis: thalassemia

syndromes       Structurally abnormal globin synthesis

(hemoglobinopathies): sickle cell anemia, unstable hemoglobins

Page 12: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Acquired     Membrane defect:

paroxysmal nocturnal hemoglobinuria

Page 13: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Extrinsic(extracorpuscular)abnormalities   Antibody mediated    Isohemagglutinins:

transfusion reactions, erythroblastosis fetalis (Rh disease of the newborn)   

 Autoantibodies: idiopathic (primary), drug-associated, systemic lupus erythematosus

Page 14: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Mechanical trauma to red cells

Microangiopathic hemolytic anemias: thrombotic thrombocytopenic purpura, disseminated intravascular coagulation   

Infections: malariaToxins like clostodium toxinMarathon running and drumbeatingChemical injury like lead poisoningHypersplenism and defective cardiac valves.

Page 15: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Mechanical traumaRed blood cell

fragments, burr cells, and helmet cells are associated with either

microangiopathic hemolytic anemia or mechanical red cell destruction.

In patients with prosthetic valves, red blood cells are exposed to excessive shear and turbulence

in the circulation, causing damage from mechanical trauma

Page 16: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

RED CELL INDICESMCV, MCH MCHC, RDW

Page 17: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Classification depending on Red cell sizeNormocyticMicrocyticMacrocyticDegree of hemoglobinization the color of the

red cellNormochromicHypochromicHyperchromic

Page 18: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Mean cell volume(MCV) is average volume of red cell expressed in femtolt(FL)

Normal-82 to96 flDecreased in iron def anemia

Page 19: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Mean cell hb(MCH) is average mass of the Hb expressed in Picogram

Normal 27 to37 picogramDecreased in iron deficiency anemia

Page 20: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

MCHC(Mean cell Hb concentration) is average concentation of Hb in a given packed red cell.

Male-33-37g/dl female-33-37g/dl

RDW Red cell distribution width 11.5-14.5

Page 21: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Hemoglobin- men-13.6-17.2 g/dl women-12.0-15.0 g/dlHematocrit (HCT) Men- -39-49% women- 33-43% Red cell count ×106/mm3 Men4.3-5.9 Women-3.5-5.0 Reticulocyte count 0.5-1.5%

Page 22: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Hemolytic anemia Hemolytic anemiaAnemia's that are associated with accelerated

destruction of red cells are termed hemolytic anemias.

Destruction can be caused by either inherent (intracorpuscular) red cell defects, which are usually inherited, or

external (extracorpuscular) factors, which are usually acquired

Page 23: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

HEMOLYTIC ANEMIAS

General features of hemolytic anemias.

(1) an increased rate of red cell destruction,

(2) a compensatory increase in erythropoiesis that results in reticulocytosis, and

(3) Accumulation of Hb degradation products

Page 24: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Intravascular hemolysisDestruction of red cells can occur within the

vascular compartmentExtravascular hemolysis.Red cell destruction within the cells of the

mononuclear phagocyte (reticuloendothelial) system

Page 25: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Clinical features of extra vascular hemolysisExtravascular hemolysis needs alteration in

RBC shape to less deformable to pass thro the spllenic sinusoids

Features1.Anemia2.Jaundice 3.Splenomegaly.

Page 26: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Intravascular hemolysis causesMechanical traumaBy defective cardiac valves thrombotic Narrowing of the

microcirculationComplement fixationIntracellualr parasites(Malarial parasite)Toxic injuries

Page 27: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Clinical features

1.Anemia2.Hbglobinemia3.Hemoglobinuria4.Hemosiderinuria. Massive intravascular hemolysis sometimes

leads to acute tubular necrosis (Free iron damamging the tubular cells)

Page 28: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

HEMOGLOBIONURIALarge amount of Hb is released from the

lysed RBCs bound to heptoglobin cleared by MNPS and depletion of heptoglobin occurs and remaining free Hb oxidizes to methhemoglobin which is brown in color causing when excreted in urine give rise to hemoglobinuria

Page 29: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

JaundiceHb bounded to heptoglobin form complex is

cataboliseed to bilirubin in MNPs leads to jaundice.

The heme converts to conjugated and uncongugated bilirubin and excess of unconjugated bilirubin leads to icterus.

Page 30: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

HemosiderosisSome Hb release iron which accumulates in renal tubular cells cause renal hemosiderosis.(also renal tubular necrosis)

Page 31: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

There is a raise in uncongugated bilirubin in hemolytic anemia

Also formation of gall stones.

Page 32: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Hereditary Spherocytosis

The inherited disorder is caused by the intrinsic defect in the red cell membrane skeleton that leads RBC to spheroid,and vulnerable to splenic sequestration and destruction.

It is a Autosomal dominant, in ¾ of the cases.Common in Northern Europe25% of patients have a more severe

autosomal recessive form of the disease.

Page 33: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

PATHOGENESISIn HS the primary abnormality resides in one

of a group of proteins.The major protein in this skeleton is spectrin,The mutations is that they weaken the

vertical interactions between the membrane skeleton and the intrinsic membrane proteins

Page 34: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Hereditary spherocytosisMild to moderate

hemolytic anemia can lead to splenomegaly, jaundice, and pigmented gallstones.

.

common defect involves mutations in the gene that codes for ankyrin

Page 35: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

In all types of HS the red cells have reduced membrane stability and consequently lose membrane fragments after their release into the periphery,

Blood smears showasSpherocytosisReticulocytosisRaised MCHC due to dehydration caused

by loss of H2o and K

Page 36: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Clinical Course anemia, splenomegaly, and jaundice.Because of their spheroidal shape, HS red

cells show increased osmotic fragility when placed in hypotonic salt solutions, a characteristic that is helpful for diagnosis

Pigment stones 40 to 50% of the cases

Page 37: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Complications

Complications 1. Aplastic crisis due to Infection by parvovirus2.Hemolytic crisis3.Gall stonesTreatmentSplenectomy

Page 38: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

HEREDITARY SPHEROCYTOSIS

Genetic defects affecting ankyrin, spectrin, usually autosomal dominant

Children, adults

Anemia, hemolysis, jaundice, splenomegaly, gallstones (what kind?)

Page 39: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Glucose-6-Phosphate Dehydrogenase Deficiency

Red cells are subjected to injuries by exo or endogenous oxidants

Any abnormality in HMP shunt or glutathione metabolism result in deficient in enzyme function and reduces RBC to protect themselvs against oxidants and leads to hemolysis

Page 40: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

G6PD genetic variants are,G6PD AAnd G6PD Mediterranean, most common in Middle east countries and clinically more significant.

Page 41: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

A- and Mediterranean are most significant types

Page 42: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

G6PD is a X linked recessive disorderMost of these cases are harmless.The deficiency is caused by exposure that

generate oxidative stressMainly infectionsViral hepatitisPneumoniaTyphoid fever

Page 43: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Drugs and certain foods like fava beansDrugs areAntimalarialsSulfonamidesNitrofurantoinIt can cause both intra and extravascular

hemolysis

Page 44: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

G6 PD deficiency anemiaHeinz bodies consist

of denatured HbFava beans

Page 45: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

G6PD

BITE CELL

Page 46: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

G6PD functionsRegenerates NADPH, allowing

regeneration of glutathioneProtects against oxidative stressLack of G6PD leads to hemolysis during

oxidative stressInfectionMedicationsFava beans

Oxidative stress leads to Heinz body formation, extravascular hemolysis

Page 47: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Presence of Heinz bodies is hall mark of G6Pd deficiency

Oxidants cause cross linking of sulfhydryl groups on globin chain and denature and membrane bound precipitates called as Heinz bodies also responsible for intravascular hemolysis and less deformable leads to extravascular hemolysis.

Page 48: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

The hemoglobinopathiesThe hemoglobinopathies are a group of

hereditary disorders that are defined by the presence of structurally abnormal hemoglobins

Sickle Cell Anemia It is a common herditary Hb nopathy occurs

primarily in individuals of African descent.

On average, the normal adult red cell contains 96% HbA (α2β2), 3% HbA2 (α2δ2), and 1% fetal Hb (HbF, α2γ2).

Page 49: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

SICKLE CELL ANEMIASickle cell anemia is caused by mutations in

globin gene.Substitution of valine for glutamic acid at the

sixth position of the β-chain produces HbS

About 8 to 10% of African American are heterozygous individuals it remain asymptomatic as sickle cell trait.

Page 50: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Etiology and Pathogenesis

Etiology and Pathogenesis Upon de oxygenation, Hb S molecules undergo polymerization, a process also referred to as gelation or crystallization. These polymers distort the red cell, which assumes an elongated crescentic, or sickle, shape.

Page 51: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Sickling of red cells is initially reversible upon reoxygenation;

Membrane damage occurs with each episode of sickling, and eventually the cells accumulate calcium, lose potassium and water, and become irreversibly sickled.

Page 52: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

The presnce of HBS responsible for the clinical manifestations

Chronic hemolysis.Microvascular occlusion,Tissue damage

Page 53: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

sickle cell traitIn Heterozygote ie in sickle cell trait

The HbS is 40% and HbA is 60%.The remaining is HbA which in turn prevent HbS polymerization, so sickling is very unlikely.

Only in profound Hypoxic condition it can cause anemia.

Page 54: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Why children remain asymptomatic till 5 to 6 months?

Hereditary persistence of HbF in these people the sickle cell disease is less severe.

Another variant Hb C Lysine is substituted for glutamate.

Page 55: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

HbF also prevents the HbS polymerization so they remain asymptomatic

In some children th HbF remain higher level and sickling is very less.

But HbC which causes the increase in the HbS and polymerization

Page 56: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

MCHC levelsIncrease in the MCHC also increase the

sicklingIntracellular PHDecrease in Ph facilitates the sicklingTransit time of red cells through

microvascular beds.

Page 57: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Major consequences stem from the sickling of red cells

chronic extravascular hemolytic anemiamicrovascular obstructionsresult in ischemic tissue damage and pain

crises

Page 58: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

PATHOGENESIS OF MICROVASCULAR OcclusionMicrovascular occlusion depends on red cell

membrane damage and factors like Inflammation tend to slow or arrest rbcs

movement thr microvaculature.Sickle cells exhibit high adhesion moledules

and are sticky.The stagnation of rbcs causes Obstruction,hypoxia and more sickling.

Page 59: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

THROMBOSIS

Depletion of NO occurs as released Hb from sickled rbcs bind to the NO and NO level decreases causes more narrowing of vessels platelet aggregation, red cell stasis and thrombosis.

Page 60: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Clinical findings

Clinical findings Dactylitis (hand-foot syndrome)Painful swelling of hands and feet2. Acute chest syndromeBy chest infections esp sterp pneumonia and Fat emboli3. central nervous system stroke,

Page 61: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related
Page 62: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Dactilitis

Dactylitis Hand Foot Syndrome Images - Image Results

                                  

Page 63: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Sickle cell anemia

Page 64: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Acute chest syndrome and stroke are the two leading causes of ischemia-related death

4. aplastic crisisThere is transient decrease in erythropoisisDue to infection by parvovirus and leads to

anemia5.Spenic sequestration crisisThere is massive entrapment of sickled cells

into spleen leading splenic enlargement.

Page 65: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Hypovolemia and shock and sometime to death.

6.AutospleneetomySpleen enlarges to certain extent in

childhood Spleen is fibrosed and diminish in size called

auto spenectomy7,Vasoocclusive crisis also called pain crisis

Page 66: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Due to hypoxia and infarction cause severe pain

AcidosisInfections and dehydration can trigger the

pain crisis

More susceptible to infections by Salmonella,Strp pneumonia and H influenza.

Page 67: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Laboratory findingsHb electrophoresisDemonstrate HbSFetal DNA analysis by amniocentesisPeripheral blood findingsthere are sickle cells and targel cells.Hb concentration decreased.

Page 68: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Treatment and PrognosisHydroxyurea has beneficiary effectIt increases the HbF levelIt has anti-inflammatory effectAlso long term use of folic acidVaccination against H influenza and

Sterptococcal. P

Page 69: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

IMMUNE HEMOLYTIC ANEMIA General principalsAll require antigen-antibody reactionsTypes of reactions dependent on:

Class of AntibodyNumber & Spacing of antigenic sites on cellAvailability of complementEnvironmental TemperatureFunctional status of reticuloendothelial system

ManifestationsIntravascular hemolysisExtravascular hemolysis

Page 70: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Antibodies combine with RBC, & either1. Activate complement cascade, &/or2. Opsonize RBC for immune system

If 1, if all of complement cascade is fixed to red cell, intravascular cell lysis occurs

If 2, &/or if complement is only partially fixed, macrophages recognize Fc receptor of Ig &/or C3b of complement & phagocytize RBC, causing extravascular RBC destruction.

Page 71: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Immune Hemolytic anemiaImmune Hemolytic anemiaCaused by antibodies that bind to RBC

leading to premature destructionCalled autoimmune hemolytic anemiaBut it triggered by ingestion of drugs so

called Immune Hemolytic Anemia.

Page 72: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Two types of IHAWarm antibody type Cold antibody (agglutinin) type

Page 73: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Warm IHAIt is more common in women than men

Also in patients with SLEDrug induced methyldopa, penicillin,

quinidine

Page 74: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Warm antibody type is more common (48% to 70%)and are of primary or idiopathic(50%)

Secondary to SLE, Lymphomas,leukemias and other malignancy.

Page 75: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Most causative antibody is IgG IgG and sometime IgA antibodies are present

The IgG coated red cell binds to fc receptors of phagocytes which remove red cell membrane causing spherocytosis cause splenomegaly.

Page 76: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Immune Complex MechanismQuinidine, Quinine, Isoniazid

“Haptenic” Immune MechanismPenicillins, Cephalosporins

True Autoimmune MechanismMethyldopa, L-DOPA, Procaineamide,

Ibuprofen

Page 77: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Warm antibody IHAUsually IgG antibodiesFix complement only to level of C3,if at allImmunoglobulin binding occurs at all tempsFc receptors/C3b recognized by

macrophages; Hemolysis primarily extravascular70% associated with other illnessesResponsive to steroids/splenectomy

Page 78: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

HAPTEN MECHANSIMDrug binds to & reacts with red cell surface

proteinsAntibodies recognize altered protein, ± drug,

as foreignAntibodies bind to altered protein & initiate

process leading to hemolysis

Page 79: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Auto antibody modelAlpha Methyl dopa an antihypertensive drug.

This drug initiates the formation of anitbody against the intrinsic red cell antigen, in particular Rh antigens,

10% patients taking alpha methyldopa develop auto antibodies.

Page 80: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Warm antibody immune hemolytic anemiaA 32-year-old woman who has recently

started taking α-methyldopa develops dark, tea-colored urine. Physical examination reveals mild scleral icterus, a low-grade fever, and mild hepatosplenomegaly. Examination of her peripheral blood reveals many microspherocytes, while laboratory examination finds a positive Coombs’ test

Page 81: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Immune Complex Mechanism

Drug & antibody bind in the plasmaImmune complexes either

Activate complement in the plasma, orSit on red blood cell

Antigen-antibody complex recognized by RE system

Red cells lysed as “innocent bystander” of destruction of immune complex

REQUIRES DRUG IN SYSTEM

Page 82: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Hemolytic transfusion reactionCaused by recognition of foreign antigens

on transfused blood cellsSeveral types

Immediate Intravascular Hemolysis (Minutes) - Due to preformed antibodies; life-threatening

Slow extravascular hemolysis (Days) - Usually due to repeat exposure to a foreign antigen to which there was a previous exposure; usually only mild symptoms

Delayed sensitization - (Weeks) - Usually due to 1st exposure to foreign antigen; asymptomatic

Page 83: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Cold antibody IHAMost commonly IgM mediatedAntibodies bind best at 0 to 4 degree C.Fix entire complement cascadeLeads to formation of membrane attack

complex, which leads to RBC lysis in vasculature

Typically only complement found on cells90% associated with other illnessesPoorly responsive to steroids, splenectomy;

responsive to plasmapheresis

Page 84: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Cold antibody IHAMost commonly IgM mediatedAntibodies bind best at 30º or lowerFix entire complement cascadeLeads to formation of membrane attack

complex, which leads to RBC lysis in vasculature

Typically only complement found on cells90% associated with other illnessesPoorly responsive to steroids, splenectomy;

responsive to plasmapheresis

Page 85: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Cold aglutinin present in 15 to 30% of cases,Antibody is IgMBy IgM antibodies that bind red cells at low

temp.Also seen following infection like Mycoplasma pneumonieEB virusCMV and H, inflenza and HIVB cell lymphomas

Page 86: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Ig M antibody binds to RBCs in the body site where the temp is at low level like 30degree C. hands, toes and ear.

As the blood recirculate these Immunoglobulins detach before the complement mainly the C3b which is a opsosin and the RBCS caught by the phagocytes and hemolysisis occur

Page 87: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

CFJaundiceHepatosplenomegalyRaynauds phenomenon

Page 88: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

DiagnosisDirect coombs testIndirect coombs testTreatmentRemoval of offending drugImmunosuppressive therapy Splenectomy

Page 89: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Direct Coombs antiglobulin test.Patients RBCs are mixed with

heterogenous antisera specific for human immunoglobulins.If positive they form antibodies and cause agglutination.

Indirect Coombs antiglobulin testPatients sera taken and mixed with

commercially available RBC and the test is positive if clumping or agglutination occurs

Page 90: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

ThalassemiaThalassemia The thalassemias are a heterogeneous group of inherited disorders caused by mutations that decrease the rate of synthesis of α- or β-globin chains. deficiency of hemoglobin, with additional secondary red cell abnormalities.

Page 91: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

BETA THALASSEMIAS Molecular pathogenesisCaused by mutations that decreases the

synthesis of beta globin chainThe β-globin mutations associated with β-

thalassemia fall into two categories: (1) β0, in which no β-globin chains are produced; and (2) β+, in which there is reduced (but detectable) β-globin synthesis.

Page 92: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Splicing mutations common cause for beta + Thalassemia

Chain terminator mutations cause for beta 0 thalassemia

Promoter region mutations some normal beta globin synthesized so beta + Thalassemia.

Page 93: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Unpaired α chains form insoluble aggregates that precipitate within the red cells and cause membrane damage that is severe enough to provoke extravascular hemolysis

In severe Thalassemia leads to ineffective erythropoisis

In turn leads to excessive iron reabsorption in the gut leads to hemochromatosis, cardiac failure and death.

Page 94: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Clinical Course β-thalassemia major manifests itself

postnatally as HbF synthesis diminishesGrowth retardationAnemia,Repeated blood transfusion leads to iron

overload due to increase absorption.Iron overload on heart cause usually death.

Page 95: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Diagnosis

Hb electrophoresisReduction in HbAIncreased HbFMicrocytic hypochromic anemiaAnisocytosisPoilkilocytosisTarget cellsReticulocyte count slightly raised

Page 96: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Beta thalassemia majorThe correct answer isHemoglobin A Hemoglobin A2

Hemoglobin Fa. Increased Increased Increasedb. Increased Increased Decreasedc. Increased Decreased Increasedd. Decreased Increased Increasede. Decreased Decreased Decreased

Page 97: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Tear drop cells

Page 98: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related
Page 99: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

ALPHA THALASSEMIASInherited deletions that results in reduced or

absent synthesis of alpha globin chain.So unpaired gamma in fetal life or beta chain

in adultsThese are soluble so hemolysis and

ineffective erythropoiesis is less severe than beta thalassemia.

Page 100: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Excess of unpaired gamma globin forms tetramers known as Hemoglobin BARTS.

The unpaired beta globins forms tetramers known as HbH.

Page 101: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Different types of alpha thalassemias1.Silent carrier state(deletion of single alpha globin gene)

2.alpha thalassemia trait(2 Alpha gene deletion)

3.Hb H disease(3 alpha gene deletion)

4.Hydrops fetalis(4 alpha globin gene deletion)

Page 102: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Hemolytic Anemias Resulting from Mechanical Trauma to Red Cells

cardiac valves like bioprosthetic or mechanical valves.

the narrowing and partial obstruction Traumatic hemolytic anemia physical blows (e.g., marathon racing and

bongo drumming

Page 103: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Microangiopathic hemolytic anemia1.disseminated intravascular coagulation due

to intravascular deposition of fibrin. 2.malignant hypertension, 3.SLE, 4.thrombotic thrombocytopenic purpura,

5.hemolytic-uremic syndrome, 6.disseminated cancer

Page 104: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

The morphologic alterations in the injured red cells

(schistocytes) "burr cells," "helmet cells," and "triangle cells“.

Page 105: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Tear drop RBC

Page 106: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Helmet cells

Page 107: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Microangiopathic Hemolytic AnemiaCausesVascular abnormalities

Thrombotic thrombocytopenic purpuraRenal lesions

Malignant hypertension Glomerulonephritis Preeclampsia Transplant rejection

Vasculitis Polyarteritis nodosa Rocky mountain spotted fever Wegener’s granulomatosis

Page 108: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Vascular abnormalities AV Fistula Cavernous hemangioma

Intravascular coagulation predominantAbruptio placentaeDisseminated intravascular coagulation

Page 109: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

PNH(PARAOXYSMAL NOCTURNAL HEMOGLOBINURIA)Clonal cell disorderOngoing Intra- & Extravascular

hemolysis; classically at nightTesting

Acid hemolysis (Ham test)Sucrose hemolysisCD-59 negative (Product of PIG-A gene)

Acquired deficit of GPI-Associated proteins (including Decay Activating Factor)

Page 110: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

GPI links a series of proteins to outer leaf of cell membrane via phosphatidyl inositol bridge, with membrane anchor via diacylglycerol bridge

PIG-A gene, on X-chromosome, codes for synthesis of this bridge; multiple defects known to cause lack of this bridge

Absence of decay accelerating factor leads to failure to inactivate complement & thereby to increased cell lysis

Page 111: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

ANEMIAS OF DIMINISHED ERYTHROPOIESISANEMIAS OF DIMINISHED ERYTHROPOIESIS

Decreased red cell production commonly due to nutritional deficiency

Bone marrow failureInfiltrative disorder leads to marrow replacement

Page 112: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Megaloblastic anemia

Megaloblastic anemiaImpairment in a DNA synthesis leads to

morphologic changes to erythroid precursor and RBCS.

Mainly Thymidine synthesis.Two types-1. pernicious anemia due to Vit B12

deficiency2.Folic acid deficiency

Page 113: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Vitamin B12 deficiency

1.Nutritiomal2.Impaired absorption A. Intrinsic factor deficiency Pernicious anemia B Gastrectomy

Page 114: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

3.Malabsorption syndromeDiffuse intestitinal diseaseLymphomaAnd systemic sclerosisIleal resectionIlelitisParasitic uptake Fish tapeworm

infestation

Page 115: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Folic acid deficiency

1.Decreased intakeInadequate intakeInfancy and alcoholism2.Impaired absorption AnticonvulsantsOral contraceptive pillsMalabsorption states

Page 116: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Increased loss HemodialysisIncreased demandPreganancyInfancyDisseminated caFolic acid antagonist

Page 117: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Metabolic role of Vit B12 and Folate

They are coenzymes for the synthesis

Of Thymidine in turn impair metabolism result in defective nuclear maturation and block cell division and leads to nuclear and cytoplasmic asynchrony.

Page 118: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

MORPHOLOGYPancytopenia(All myeloid lineages are

affected)Change in RBC size and shapes(Macrocyte,

and macroovalocyte)HyperchromicHypersegmented neutrophilsHyperplasia of Bone marrowMild ineffective hematopoiesis.

Page 119: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related
Page 120: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related
Page 121: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related
Page 122: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Anemia due to Vit B12 deficiency

Pernicious anemiaIt is a autoimmune disorder caused by defect

in intrinsic factor productionChronic gastric atrophy leads to loss of

parietal cells Increased incidence of Pernicious in Blood

Group A

Page 123: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related
Page 124: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related
Page 125: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related
Page 126: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related
Page 127: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Methyl cobalamine transfers the methyl group to homocysteine to produce

MethionineDeficiency of Vit B12 traps N5 methyl FH4Deficiency of folate or Vit B12.. increases

plasma homocysteine

Page 128: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Pernicious anemia

Page 129: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

also found in elderly persons with chronic gastritis

MorphologyPeripheral blood smear showsMacrocytesHyperchromaticAnisocytosisPoilkilocytosis

Page 130: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Nucleated red cell progenitorNeutrophils hypersegmented bone marrow findings Hyper cellularIncreased hematopoietic precursor

Page 131: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Clinical features

Smooth, sore tongue, glazy ,shiny and beefy tongue with atrophy of papillae

Atrophic glossitisNeurologic diseasePeripheral neuropathy with sensor motor

dysfunctionb. Sub acute combined degeneration

(demyelination) of the spinal cord

Page 132: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

DiagnosisModerate megaloblastic anemiaLeukopeniaLow serum B12 levelsElevated levels of Homocysteine and

methyl melonic acidLow reticulocyte countSchilling testSeru antibodies to intrinsic factor for

pernecious anemia

Page 133: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

methylmalonic acidVitamin B12 is important in DNA synthesis; therefore

hematological manifestations of B12 deficiency aremegaloblastic anemia and pancytopenia. Vitamin B12 (deoxyadenosyl cobalamin) also serves asa cofactor for methylmalonyl CoA mutase. [This

enzyme catalyzes the conversion of methylmalonyl CoA into succinyl CoA.

Succinyl CoA is the final product of fatty acid oxidation that enters citric acid cycle. Deficiency of B12 leads to an accumulation of methylmalonic acid.

Page 134: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Elevated levels of methylmalonic acid result in myelin synthesis abnormalities. Neurological damage associated with B12 deficiency includes subacute, combined degeneration of the posterior and lateral spinal columns. Axonal degeneration of peripheral nerves is also seen. Loss of position and vibration sensation, ataxia, and spastic paresis result. Increased serum levels of methylmalonic acid are diagnostic of vitamin B12 deficiency

Page 135: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related
Page 136: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related
Page 137: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related
Page 138: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Folate deficiency

Page 139: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Aplastic Anemia

Aplastic anemia is a disorder in which multipotent myeloid stem cells are suppressed, leading to marrow failure and pancytopenia.

Page 140: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Etiology and Pathogenesis

Most of the cases the cause is unknown65% of the cases are idiopathic.Acquired causes Drugs and chemicals., antineoplastic drugs (e.g., alkylating agents,

antimetabolites), benzene, and chloramphenicol. Sulfonamides

Page 141: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Chemical agentsBenzene,chloramphenicolAntimetabolitesPenicillamines gold saltsPhysical agentsWhole body irradiationViralHepatitis unknown virusEB virus, Herpes zosterInherited (Fanconi anemia)

Page 142: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

certain viral infections, most often community-acquired viral hepatitis.

CMV infections and EB virus

Page 143: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

PATHOGENESIS1. immunologically mediated suppression(T cells)

2.Intrensic abnormality in the stem cell.

Page 144: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

1.Following exposure to chemicals, or viral infections or drugs, the stem cells are antigenic ally altered that evokes the Immune response and the T lymphocytes stimulate cytokines IF gamma and TNF which in run prevents the proliferation and differentiation of stem cells.

Page 145: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

2.Genetic damage that limits the differentiation and proliferation of the stem cells.

Page 146: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

MorphologyThe bone marrow in aplastic anemia typically is markedly hypocellular,

with greater than 90% of the intertrabecular space being occupied by fat.

Bone marrow biopsy yields dry tap

Page 147: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Anemia may cause fatty change in the liver, and thrombocytopenia and granulocytopenia may result in hemorrhages and bacterial infections,

Page 148: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

weakness, pallor, and dyspnea. Thrombocytopenia often presents with petechiae and ecchymoses

. Granulocytopenia may be manifested only by frequent and persistent minor infections or by the sudden onset of chills, fever, and prostration.

Page 149: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Splenomegaly is charestically absent.red cells are normocytic and normochromic,

although slight macrocytosis is occasionally present; reticulocytes are reduced in number.

TreatmentThe idiopathic form has a poor prognosis if

left untreated. Bone marrow transplantation is an extremely effective form of therapy

Page 150: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

The prognosis of marrow aplasia is quite unpredictable.,

withdrawal of toxic drugs may lead to recovery in some cases.

The idiopathic form has a poor prognosis if left untreated.

Bone marrow transplantation is an extremely effective form of therapy,

especially if performed in nontransfused patients younger than 40 years of age . benefit from immunosuppressive therapy

Page 151: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Myelophthisic Anemia Extensive replacement of the marrow by

tumors or other lesions. It is most commonly associated with

metastatic breast, lung, or prostate cancerAdvanced tuberculosis, lipid storage

disorders, and osteosclerosis can produce a similar clinical picture.

Page 152: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Iron Deficiency Anemia

Most common form of nutritional deficiencyTotal body Fe content in women 2gm for

men 6gmIt is present in 2 compartments1.Storage compartment as Ferritin stored in liver, spleen and bone

marrow and skeletal muscleHemosiderin

Page 153: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Functional compartment 80% of the total iron in Hb

Daily requirementsFor men 7 to 10mgWomen7 to 20mgHealthy females have low storage of iron

due to Menstrual loss every month compared to men.

Page 154: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Causes of iron deficiency anemia1.Decreased dietary intake2.Impaired absorption3.Increased demand in pregnancy and lactation, toddlers and children.

4.Chronic blood loss.

Page 155: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Pathogenesis

Iron is transported by binding to iron binding protein called transferrin

Transferrin levelIn men 120micogram/dlIn women 100micogram/dlMicrocytic hypochromic anemiaThe serum ferritin level fallsThe hepcidin levels decreases.

Page 156: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Clinical features

Fatigue,PalpitationsDyspneaPallorKoilonychia spoon shaped nails bedsDepletion of iron from the CNS lead to eating

mud or clay.

Page 157: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Plummer Vinson syndrome

GlossitisOesophageal webHypochromic microcytic anemia

Page 158: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Factors enhance the iron absorption are

Ascorbic acid and aminoacidsFactors that inhibit the iron

absorption are,Tannates (present in tea)Phytates,phosphates

Page 159: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Diagnosis

Increased total iron binding capacityDecreased ferritin levelsDecreased total serum ironIncrease in the transferrin receptorsReticulocytosisThrombocytosisIncreased RDWLow hepcidin levels

Page 160: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Chronic diseases leading to anemia

Chronic infectionsChronic immune disorders like Rheumatoid arthritis

Neoplasms

Page 161: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Diagnosis

1.Increased ferritin level2.Decreased total iron binding capacity.

3.Increased hepcidin,4.Normochromic normocytic or microcytic hypochromic

Page 162: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Hypochromic, microcytic red cells.

The serum iron levels, The total iron-binding

capacity,Transferrin saturation

to be reduced. A bone marrow

biopsy reveals the iron to be present mainly within macrophages.

Anemia of chronic disease

Page 163: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Koilonychia Fe deficiency

Page 164: RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

Serum Iron TIBC serum ferritin transferrin

A) Normal Normal Normal Normal

B) Low High Low High

C) Normal /High Normal/low High Low

D) Low Low Normal to high Low