Week 2: Hemolytic Anemia

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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

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Normocytic Anemia

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

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Acute Hemorrhage

• No changes in CBC until plasma volume increases
• Later, reticulocytosis

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Hypoproliferative Anemia

• Pancytopenia
• lt 25 BM cellularity
• Low retic count
• Bone marrow defect
• Immunologic suppression
• Growth Factor deficiency
• Abnormal stem cells

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Acquired Aplastic Anemia

• Idiopathic
• Drugs and chemicals (eg, chloramphenicol,
  benzene, insecticides)
• Radiation
• Virus
• Paroxysmal nocturnal hemoglobinuria

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Constitutional Aplastic Anemia

• Fanconis anemia
• Chromosomal breaks

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Pure Red Cell Aplasia PRCA

• Infections
• Drugs
• Diamond-Blackfan syndrome
• No EPO deficiency

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Hemolytic Anemia

• Intravascular vs extravascular
• Bilirubin metabolism
• Types
• Membrane defect
• Metabolic defect
• Extracorpuscular

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Evidence of Hemolysis

• Low RBC survival with chromium tagging study
• Unconjugated bilirubin
• Plasma Hb
• Decreased serum haptoglobin

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Evidence of Erythropoiesis

• Polychromasia
• Increased reticulocyte
• Shift macrocytosis
• Hypercelluar BM

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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
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Membrane Defect

• Spherocytosis
• Elliptocytosis
• PNH (sensitivity to complement lysis -- sugar
  water test, Hams test)
• Stomatocytosis (possibly Rh null)

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Spherocytes
Elliptocytes
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Osmotic Fragility
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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

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Lab Tests for PNH

• Acidified serum lysis test (Hams 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

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Stomatocytes
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Metabolic Defect

• G6PD deficiency
• Hexose monophosphate shunt
• Most common RBC enzyme defect, gt50 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

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Heinz body preparation with Crystal
violet Unstable hemoglobin
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Extracorpuscular Factors

• Antibodies
• Autoimmune
• Isoimmune
• Drugs, antibiotics
• Fresh water

• Abnormal plasma lipids
• Acanthocytosis
• Venom
• Snake
• Spider
• Bee

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Extracorpuscular Factors

• Trauma
• DIC
• Hemolytic uremic syndrome (HUS)
• TTP
• Angiopathy
• Heat
• Heart valves
• March hemoglobinuira

• Microorganisms
• Malaria
• Babesia
• Clostridium
• Gram negative endotoxin

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Schistocytes
Malaria