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Week 2: Hemolytic Anemia

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1 Week 2: Hemolytic Anemia
Normocytic anemia Fanconi anemia Diamond-Blackfan (PRCA) Types of hemolysis Evidence of hemolysis Reticulocyte G6PD deficiency Heinz bodies PK deficiency Cytoskeleton Spherocytosis Elliptocytosis PNH

2 Normocytic Anemia Acute hemorrhage Hypo-proliferative
Acquired aplastic anemia Constitutional aplastic anemia Pure red cell aplasia (PRCA)

3 Acute Hemorrhage No changes in CBC until plasma volume increases
Later, reticulocytosis

4 Hypoproliferative Anemia
Pancytopenia < 25% BM cellularity Low retic count Bone marrow defect Immunologic suppression Growth Factor deficiency Abnormal stem cells

5 Acquired Aplastic Anemia
Idiopathic Drugs and chemicals (eg, chloramphenicol, benzene, insecticides) Radiation Virus Paroxysmal nocturnal hemoglobinuria

6 Constitutional Aplastic Anemia
Fanconi’s anemia Chromosomal breaks

7 Pure Red Cell Aplasia PRCA
Infections Drugs Diamond-Blackfan syndrome No EPO deficiency

8 Hemolytic Anemia Intravascular vs extravascular Bilirubin metabolism
Types Membrane defect Metabolic defect Extracorpuscular



11 Evidence of Hemolysis Low RBC survival with chromium tagging study
Unconjugated bilirubin Plasma Hb Decreased serum haptoglobin

12 Evidence of Erythropoiesis
Polychromasia Increased reticulocyte “Shift” macrocytosis Hypercelluar BM



15 Correcting Retic Count
Retic Index = Retic % x Patient Hct Normal Hct Absolute Retic = Retic % x RBC/mm3 Retic Production Index = Retic Index Days in circulation

16 Membrane Defect Spherocytosis Elliptocytosis
PNH (sensitivity to complement lysis -- sugar water test, Ham’s test) Stomatocytosis (possibly Rh null)

17 Spherocytes Elliptocytes


19 Osmotic Fragility

20 Paroxysmal Nocturnal Hemoglobinuria
Hematopoietic stem cell disorder Mutation of phosphatidylinositol glycan class A (PIG-A) gene Glycosylphosphatidylinositol (GPI) anchors membrane proteins Without GPI, unable to regulate completment activities on membrane Hemolysis is pH dependent Thrombosis can occur

21 Lab Tests for PNH Acidified serum lysis test (Ham’s test): PNH cells lyse due to complement activation in acidified serm Sugar water (sucrose hemolysis) test: RBCs sensitive to complement will lyse in sucrose and serum Flow cytometry: lack of CD59 on RBCs, or lack of CD59 or CD55 on granulocytes

22 Stomatocytes

23 Metabolic Defect G6PD deficiency Hexose monophosphate shunt
Most common RBC enzyme defect, >50 variants X-linked Low glutathione due to low NADPH Oxidative lysis, Heinz bodies, spherocytic Primaquine, fava beans Pyruvate kinase deficiency Glycolysis Low RBC ATP level Non-spherocytic B12 and folate deficiency Macrocytic HJ bodies Hemoglobinopathies Poikilocytosis Abnormal Hb

24 Heinz body preparation with Crystal violet
Unstable hemoglobin

25 Extracorpuscular Factors
Antibodies Autoimmune Isoimmune Drugs, antibiotics Fresh water Abnormal plasma lipids Acanthocytosis Venom Snake Spider Bee

26 Extracorpuscular Factors
Trauma DIC Hemolytic uremic syndrome (HUS) TTP Angiopathy Heat Heart valves “March” hemoglobinuira Microorganisms Malaria Babesia Clostridium Gram negative endotoxin

27 Schistocytes Malaria

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