Haemolytic anaemias

Atifa Ambreen

Introduction

• Mean life span of a RBC-120days• Removed Extravascularly by- Macrophages of RE system.

Intravascular haemolysis occurs in some pathological disorders

Normal red blood cell breakdown.This takes place extravascularly in the macrophagesof the reticuloendothelilial system

Hemolytic Anemia

• Definition:– Those anemias which result from an increase in RBC destruction

• Classification:– Congenital / Hereditary– Acquired

Classification of Hemolytic Anemias

• Hereditary

Memeberane Hereditary spherocytosis,Hereditary elliptocytosis Metabolism G6PD Deficiency,pyruvate kinase deficiency Haemoglobin Genetic abnormalities(Hb S,Hb C,unstable)

Acquired

• Immune

Autoimmunewarm antibody typecold antibody type

Alloimmunehaemolytic transfusion reactionhaemolytic disease of newbornAllografts,especially stem cell transplantationDrug associated

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• Red cell fragmentation syndromes

March haemoglobinuriainfectionsMalaria,Clostridia

Chemical and physical agentsEspecially drugs,burns

Secondaryliver and renal disease

proxysmal nocturnal haemoglobinuria(PNH)

Laboratory evaluation of Haemolysis

• HEMATOLOGIC Extravascular Intravascular Routine blood film Polychromatophilia Polychromatophilia

• Reticulocyte count Increase increase• Bone marrow examination Erythroid Erythroid

hyperplasia hyperplasia

• PLASMA OR SERUM• Bilirubin unconjugated unconjugated• Haptoglobin Dec,Absent Absent• Plasma hemoglobin N/inc. Increase• Lactate dehydrogenase Variable increase

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• Extravascular Intravascular

• URINE• Bilirubin 0 0• Hemosiderin 0 +• Hemoglobin 0 + in severe

cases

Red Cell Membrane Defects

1.Hereditary Spherocytosis– Usually inherited as Autosomal Dominent disorder– Defect: Deficiency of Beta Spectrin or Ankyrin Loss of membrane in

Spleen & RES becomes more spherical Destruction in Spleen

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Clinical features

• Asymptomatic• Fluctuating hemolysis• Splenomegaly• Pigmented gall stones- 50%

Clinical course may be complicated with Crisis:

– Hemolytic Crisis: associated with infection– :Aplastic crisis associated with Parvovirus infection

Investigations

– Test will confirm Hemolysis– Periphral Smear: Spherocytes– Osmotic Fragility: Increased

Screen Family members

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• 2.Hereditary Elliptocytosis

Functional abnormality in one or more anchor proteins in RBC membrane- Alpha or beta spectrin , Protein 4.1

• Usually asymptomatic

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South-East Asian ovalocytosis:

• Caused by a nine amino acid deletion at he junction of the cytoplasmic and transmemberane domains of the band 3 protein

• Asymptomatic-usually• Cells oval , rigid ,resist invasion by malarial parasites• Common in malaysia , indonesia

Membrane abnormalities - Enzymopathies

• Deficiencies in Hexose Monophosphate Shunt– Glucose 6-Phosphate Dehydrogenase Deficiency

• Deficiencies in the EM Pathway– Pyruvate Kinase Deficiency

Glucose 6-Phosphate Dehydrogenase

• Regenerates NADPH, allowing regeneration of glutathione

• Protects against oxidative stress• Lack of G6PD leads to hemolysis during oxidative stress

– Infection– Medications– Fava beans

• Oxidative stress leads to Heinz body formation, extravascular hemolysis

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Investigations

– P. Smear: Bite cells, blister cells, irregular small cells, Heinz bodies, polychromasia

– G-6-PD level

2. Pyruvate Kinase Deficiency

– Deficient ATP production, Chronic hemolytic anemia

– Investigations• Priphral Smear: Prickle cells• Decreased enzyme activity

Autoimmune Hemolytic Anemia

• Result from RBC destruction due to RBC autoantibodies: Ig G, M, E, A

• Most commonly-idiopathic• Classification

– Warm Autoimmune haemolysis:Ab binds at 37degree Celsius– Cold Autoimmune haemolysis: Ab binds at 4 degree Celsius

1.Warm Autoimmune hymolysis

•Usually IgGIdiopathicSecondary causesSLE,CLL,lymphomas,Drugs(e.g.Methyldopa)

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MACROCYTE

SPHEROCYTE

IMMUNOHEMOLYTIC ANEMIA

Investigation

– e/o hemolysis, MCV – P Smear: Microspherocytosis, n-RBC– Confirmation: Coomb’s Test / Antiglobulin test

Direct Antiglobulin test

demonstrating the presence of autoantibodies or complement on the surface of the red blood cell.

Cold Autoimmune haemolysis

• Usually IgM

InfectionsMycoplasm pneumonia,infectiousmononucleosis lymphomaproxysmal cold haemoglobinuria

Investigation

• Periphral Smear: Microspherocytosis

Ig M with specificity to I or I Ag

Alloimmune

• Induced by red cell antigensHaemolytic transfusion reactionshaemolytic disease of the new bornpost stem cell graftsDrug inducedDrug-red cell membrane compleximmune complex

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