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