Normocytic normochromic anaemia Hemolytic anaemia

Hemolytic anaemia

1. HEMOLYTIC ANAEMIA Dr. OM JHA

2. Introduction Characterized by: Premature RBC destruction (less than the normal 120-day lifespan). E levated erythropoietin with increased erythropoiesis . I ncreased hemoglobin catabolites (e.g ., bilirubin ) E xcess serum bilirubin is unconjugated . U ltimate levels of hyperbilirubinemia depend on: liver functional capacity R ate of hemolysis N ormal liver  severe jaundice  rarely.

3. Contd … BM erythropoiesis  unable to compensate for degree of destruction of red cells  Anaemia d evelops. Clinical and lab findings indicates: Accelerated destruction of red cells. Compensatory marrow regeneration. Mild hemolysis  compensatory BM function adequate  No manifestation of anaemia  Compensated hemolytic anaemia .

4. Classification Location of hemolysis: Intravascular and extravascular. Source of defect causing hemolysis: Intracorpuscular defect and extracorpuscular defect Mode of onset: Hereditary and acquired disorders. Underlying mechanisms of hemolysis: Immune or Non-immune.

5. Classification

6. Contd..

7. Red Cells Destruction Extra-vascular Hemolysis Normal site of destruction of old RBCs : Spleen (80-90%). In HA  This mechanism  Exaggerated. Intra-vascular Hemolysis RBCs in circulation  get destroyed  release of Hb in plasma. Main pathway of: PNH .

8. Extravascular hemolysis O ccurs in macrophages of the spleen ( and other organs). Predisposing factors: RBC membrane injury R educed deformability Opsonization Principal clinical features are: A nemia , splenomegaly , and jaundice Modest reductions in haptoglobin a serum protein that binds hemoglobin

9. Contd … Increased unconjugated bilirubin : jaundice. Increased stercobilinogen : dark colored stool. Increased urobilinogen : high colored urine. Increased iron store: iron released from heme stored in BM.

10. Intravascular hemolysis RBCs ruptured by: Mechanical injury (e.g., mechanical cardiac valves) C omplement fixation (e.g ., mismatched blood transfusion) I ntracellular parasites (e.g ., malaria) E xtracellular toxins (e.g., clostridial enzymes ). Presentation: Anemia, hemoglobinemia , hemoglobinuria , hemosiderinuria , and jaundice Markedly reduced serum haptoglobin .

11. Contd … Characteristic findings of intra-vascular hemolysis : Hemoglobinemia Haemoglobinuria Haemosiderinuria S. Heptoglobin : decreased

12. Laboratory Findings Increase S. Bilirubun (Unconjugated). Increase Urine Urobilinogen. Increase rate of Bilirubin production. Increase S. LDH. Decrease life span of red cells. Decrease Heptoglobin.

13. Clinical Manifestations Clinical signs & symptoms depends upon: Severity of hemolysis. Duration of hemolysis. Manifestaions mostly seen in Chronic HA : Pallor Jaundice Splenomegaly Gall stones Skeletal abnormalities Leg ulcers

14. Compensatory Mechanisms To Hemolysis BM Erythroid hyperplasia: Chronic hemolysis --> Anaemia --> Increase in Erythropoietin --> BM erythroid hyperplasia. Reversal of M:E ratio . (2-4:1 --> 1:1-6). Reticulocytosis: BM erythroid hyperplasia --> rise in Reticulocytes. Mild: Hemoglobinopathies. Moderate to marked: IHA, HS, G 6 PD def.

15. Peripheral Blood Findings Polychromatophilia: Large red cells released from BM. Corresponds to reticulocytes. Nucleated RBC (nRBC): Seen in moderate to marked anaemia. Neutrophilia: Active moderate to marked hemolysis. Neutrophilia with shift to left (metamyelocyte, Myelocytes). Thrombocytosis: Acute hemolysis Numerous and large platelets.

16. Morphologic Red Cell Abnormalities Provide clue to the underlying hemolytic conditions . Spherocytes Sickle cells Target Cells Schistocytes Acanthocytes

17. Fig: Marrow aspirate smear from a patient with hemolytic anemia . There is an increased number of maturing erythroid progenitors (normoblasts).

18. Structure of RBC Membrane

19. RBC Membrane Defects

20. Hereditory Spherocytosis D/t cytoskeletal or membrane protein defects. Render RBCs spheroidal and less deformable Vulnerable to splenic sequestration and destruction. AD in 75% of patients.

21. Pathogenesis Insufficiency in several different proteins: spectrin, ankyrin, band 3, or band 4.2. Lead to reduced density of membrane skeletal components Reduced stability of the lipid bilayer. Loss of membrane fragments as RBCs age. Reduction in surface area RBCs assume a spheroidal shape. D iminished deformability. Propensity for being trapped and destroyed by splenic macrophages.

22. Fig: Reduced membrane stability in HS --> loss of RBC membrane --> formation of microspherocytes --> Ingested by splenic Macrophages.

23. Mechanism of Hemolysis in HS

24. Morphology Spherocytic RBCs are small and lack central pallor. Reticulocytosis and marrow erythroid hyperplasia. Marked splenic congestion with prominent erythrophagocytosis in the cords of Billroth.

25. Contd...

26. Clinical Features Diagnosis depends on: family history, hematologic findings, and increased RBC osmotic fragility MCHC increased: d/t cellular dehydration. Characteristic: Anemia, moderate splenomegaly, and jaundice. Clinical course: typically stable due to compensatory increases in erythropoiesis. Increased RBC turnover or diminished erythropoiesis can be problematic.

27. Contd... Parvovirus --> transient suppression of erythropoiesis --> Aplastic crisis Events that increase splenic RBC destruction ---> e.g., infectious mononucleosis --> trigger hemolytic crisis. 50% adults: chronic hyperbilirubinemia --> gallstones.

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