HEMOLYTIC ANEMIA DR Subhan Ali R HEMOLYTIC ANEMIA

HEMOLYTIC ANEMIA DR. Subhan Ali R

HEMOLYTIC ANEMIA • DEFINITION • CAUSES • • APPROACH TO DIAGNOSIS • DIAGNOSIS

DEFINITION • Anemia due to inability of the bone marrow to compensate for the degree of destruction of RBC

Normal RBC destruction • Life span 100 - 120 days • Towards the end red cell surface changes make them susceptible to phagocytosis by RES • Energy derived from glucose breakdown maintains red cell integrity

Hb metabolism • Phagocytosed RBCS release Hb • Broken down within RES • Globin back to metabolic protein pool • Porphyrin ring of heam cleaved by HO • Yields biliverdin and CO • Reduced to bilirubin

Haem degradation

Causes of hemolysis • Extra vascular • Intra vascular

Extra vascular • 80 -90% in Spleen • Others sites are bone marrow reticuloendothelial cells • • • Characteristics (1) ↑ Bilirubin - blood (2) ↑ Stercobilinogen – stool (3) ↑ Urobilinogen – urine (4) ↑ Iron store – bone marrow

Intra vascular • RBC destroyed while in circulation • Minor pathway • • • Characteristics Haemoglobinemia Haemoglobinuria Haemosiderinuria Serum haptoglobin

Causes • Two types • (A) Hereditary • • (B) Acquired

Hereditary • (A) Defect in RBC membrane • (B) Defect in globins synthesis • (C) Enzyme deficiency of glycolytic pathway • (D) Enzyme deficiency of pentose phosphate pathway • (E) Enzyme deficiency of RBC nucleotide metabolism

Acquired • (A) Immunohemolytic anemia • (B) Fragmentation syndrome • (C) Paroxysmal nocturnal haemoglobinuria • (D) Drugs & chemicals • (E) Thermal injury • (F) Infections

Defect in RBC membrane • Hereditary spherocytosis • Hereditary elliptocytosis • Stomatocytosis • Acanthocytosis (Abetalipoproteinemia)

Defect in globins synthesis • Beta Thalassemias • Alpha Thalassemias • Sickling syndromes • Unstable Hb disease

Enzyme deficiency of glycolytic pathway • Pyruvate kinase deficiency • Hexokinase deficiency

Enzyme deficiency of pentose phosphate pathway • Glucose-6 -Phosphate Dehydration deficiency (G-6 -PD)

Enzyme deficiency of RBC nucleotide metabolism • Pyrimidine-5’-nucleotidase deficiency

Immunohemolytic anemia • • Autoimmune haemolytic anaemias Due to warm antibodies Idiopathic Secondary Due to cold antibodies Cold agglutinin disease Paroxysmal cold haemoglobinuria Haemolytic disease of newborn

Fragmentation syndrome • Haemolytic uremic syndrome • Thrombotic thrombocytopenic purpura • Disseminated intavascular coagulation • Prosthetic cardiac valves

Drugs & chemicals • • Drugs Oxidant drugs Primaquine Dapson • Chemicals • Naphthalene • Nitrites and Nitrates • Oxidizing chemicals

Thermal injury • Burn • Electric shock • Heat stroke

Infections • Clostridium welchi septicemia • Bartonellosis • Cholera

APPROACH TO DIAGNOSIS • History • Clinical Examination • Laboratory Evaluation

History • • • Complaints Age at onset Development of pallor Duration of disease Jaundice Exposers to chemicals or drugs Infection , fever Color of urine Color of stool Family history

Clinical Examination • • • Pallor Jaundice Gall stone Spleenomegaly Skeletal abnormalities Leg ulcers

Laboratory Evaluation • Peripheral blood examination • Bone marrow examination • Biochemical finding • Specific test

Peripheral blood examination • RBC : - POLYCHROMATOPHILIA NUCLEATED RBC RETICULOCYTOSIS POIKILOCYTOSIS SPHEROCYTE, SICKEL CELL, TARGET CELL, SCHISTOCYTES, ACANTHOCYTE • WBC : - NEUTROPHILIA • PLATELETS : - ↑ GIANT PLATELETS

Bone marrow examination Ø ERYTHROPOISIS – HYPERCELLULAR REVERSE M: E RATIO – 1 : 1 to 1 : 6 (NORMAL 3 -7 : 1) NORMOBLASTIC REACTION PREPONDERANCE OF NORMOBLAST DYSERYTHROPOISIS (A) HOWEL JOLLY BODIES (B) ABNORMAL HEMOGLOBNISATION (C) IRREGULAR NUCLEAR BORDER (D) ABNORMAL MITOSIS • MYELOPOISIS – NORMAL • MEGAKARYOPOISIS – NORMAL

Biochemical finding • S. BILIRUBIN : - ↑ • URINE UROBILINOGEN : - ↑ • RATE OF BILIRUBIN PRODUCTION : - ↑ • S. LDH LEVELS : - ↑ • S. HAPTOGLOBIN : - ↓ • LIFE SPAN OF RBC : - ↓

Specific test • • Hemoglobinopathies Fetal Hb estimation Hb electrophoresis Sickling test Reticulocyte preparation Cytochemical stain for Hb. F Heinz body preparation

Specific test • • • Spherocytosis osmotic fragility Acidified glycerol lysis test Immune hemolytic coomb test Direct & indirect

Specific test • • • G-6 -PD deficiency Methaemoglobin reduction test Fluorescent spot test Quantitative assay Heinz body test Ascorbate - cyanide test

Specific test • P. K. deficiency • Autohemolysis test • Paroxysmal nocturnal haemoglobinuria • Ham’s acidified serum test • CD 59, CD 55

Specific test • • Bite cell haemolytic anaemias : Heinz body test Bite cell in PS Methaemoglobinaemia Spectroscopy Paroxysmal cold haemoglobinuria Landsteiner; s test