Hemolytic Anemias

1. Hemolytic Anemias Normal RBC life span = 120 days. This is shortened in hemolytic anemias. Common manifestations to all HA are anemia, jaundice, red color urine, and splenomegaly.

2. Lab tests High retic count, polychromasia RBCs, abnormal RBC shape, ↑ SUCB, ↑ SLDH2, ↑ SGOT, ↓S haptoglobin (plasma α-globulin synthesized by the liver that binds to globin of hemoglobin). Intravascular hemolysis ---- release Hb into plasma (hemoglobinemia) Plasma Hb ↑, hemosiderinuria, hemoglobinuria Extravascular hemolysis ---- by RES Mφ

3. Classification I- Hereditary II- Acquired I. Hereditary ----- A) RBC membrane defects 1. Hereditary spherocytosis (HS) 2. Hereditary elliptocytosis 3. Hereditary pyropoikilocytosis.

4. Hereditary spherocytosis (HS) * Inheritance --- AD * Incidence ---- 1:1000-4500 * Defect --- A molecular defect is present in one of membrane cytoskeleton proteins e.g. spectrin, protein3 or ankyrin leading to loss of membrane & ↓ ratio of surface area to volume causing spherocytosis. These spherocytes are less deformable than normal RBCs therefore can't traverse the splenic interstices & engulfed by splenic Mφ.

5. S&S Anemia, splenomegaly, jaundice, pigment gall stones and chronic leg ulcerations.

6. Lab tests * Blood film: spherocytes, MCV↓, MCHC↑. * Osmotic fragility test – ↑ RBC fragility on exposure to hypotonic solutions"sucrose lysis test" & autohemolysis test on 24h sterile incubation. *BMA: Erythroid hyperplasia

7. DDx * Autoimmune HA (AIHA) * Hemolysis induced by splenomegaly of cirrhosis * Clostridial infection * Snake envenomation.

8. ℞ * Splenectomy – corrects anemia but not the defect. * ± Cholecystectomy * Folic acid supplement.

9. 2. Hereditary elliptocytosis Normally elliptocyte RBCs are seen in birds & reptiles. *Inheritance --- AD * Ovalocytosis in southeast Asia * Mild hemolysis. * Osmotic fragility test is normal.

10. 3. Hereditary pyropoikilocytosis (rare) * RBCs undergo disruption at temp. of 44-45℃ (N up to 49℃) * Spectrin deficiency & defective assembly. * Responds partially to Splenectomy.

11. B) RBC enzyme defects 1. G6PD deficiency (HMPS enzyme) * Epidemiology ---- 1:200 million populations. It partially protects from malaria infection (provide defective home for merozoites). Mediterranean, African & southern China. * Inheritance X-linked recessive (Lyonization)

12. Hemolysis on exposure to oxidant stress --- * metabolic acidosis * Drugs e.g. Aspirin, antimalarial, sulfa, nitrofurantoin * Toxins e.g. moth balls (naphthalene), * Fava beans consumption (favism) S & S --- hemolysis within hours of exposure to oxidant stress. Hemoglobinuria, peripheral vascular collapse, jaundice. Episode is self-limited because only the old RBCs hemolyse Lab --- PCV↓, plasma Hb↑, SUCB↑, plasma haptoglobin↓. Blood film – Heinz bodies in RBCs (crystal violet +ve inclusions readily removed by spleen causing Bite cells) RBC enzyme level 1 month after hemolytic episode.

13. 2. Glutathione reductase def 3. Pyruvate kinase def -- AR

14. II. Acquired ---- * Normal RBCs destroyed in the circulation prematurely. * Damage mediated by Abs, toxins, or abnormalities in the circulation.

15. 1. Entrapment --- Hypersplenism Spleen efficiently traps & destroys RBCs with minimal defects. Large spleen causes pooling of RBCs in nutrient-poor environment full of phagocytic cells. Seen in inflammatory &congestive splenomegaly rather than infiltrative. Pancytopenia seen. ℞ -- Splenectomy.

16. 2. Immune hemolytic anemia Usually autoimmune, rarely alloantibodies due to blood transfusion AIHA --- of 2 types Warm Abs – IgG that reacts at normal body temp. Cold Abs – IgM react at low temp. with polysaccharide Abs (rarely IgG – Donath-Landsteiner Abs in Parox cold Hburia) S&S – Anemia, jaundice, splenomegaly

17. S&S Anemia, jaundice, splenomegaly Warm Abs – Adults, ♀ , 25% have underlying disease e.g. SLE, other collagen vascular diseases, lymphomas, drugs -- Cold Abs – arise in 2 clinical settings * Monoclonal ---- Lymphoid neoplasm, paraneoplasia * Polyclonal ---- infections e.g. Mycop pn, inf mono Acrocyanosis (bluish discoloration of extremities, nose & ear on exposure to cold. Hemolysis is also seen. PCH – tertiary syphilis, viral inf & autoimmune.

18. Dx Coomb's test +ve (antiglobulin IgG or complement) Direct --- anti-IgG or anti-C3 Abs agglutinate patient's RBCs Indirect--- serum of pt incubated with normal RBCs & Abs detected with anti-IgG. Hb↓, PCV↓, reticulocytosis (10-30%), spherocytosis. Hbemia, Hburia, hemosiderinuria in severe cases. Associated immune thrombocytopenia = Evan's syndrome Cold agglutinins- thermal amplitude of Abs, exposure to cold env

19. ℞ • No ttt for mild hemolysis. • Corticosteroids – PDN 1mg/kg bw until Hb is normal then tapering done over several months. Alternate day chronic use. • Inhibit Abs synthesis & inhibition of clearance of Ab-coated RBCs by mφ. • Splenectomy --- if pt not tolerate or not responds to steroids. • Immunosuppressant --- azathioprine, CTX (for pt not responding neither to steroids nor to Splenectomy) • IVIG ---- rapid cessation of hemolysis. • Blood Transfusion – may be needed. Ab is pan agglutinin making cross matching impossible. It can be done by adsorbing pan agglutinin from pt serum with pt RBCs from which Ab has been eluted. Serum cleared of auto-Ab tested for allo-Ab to donor bl.

20. Cold Ab Warm env Corticosteroids Chlorambucil & CTx Ttt of underlying malignancy

21. Drug –Induced HA Mechanisms – autoimm HA e.g. α-methyl dopa, --- Hapten e.g. penicillin, sulfonamides, sulfonylurea -- Innocent bystander e.g. quinine, cephalosporins.

22. 3. Trauma in the circulation * March Hburia – in Marathon runners. * Prosthetic valve – crush hemolysis * Severe calcific native valve aortic stenosis * Microangiopathic HA (MAHA) – micro thrombi in microcirculation causing RBCs trapping and fragmentation due to shearing force. a- Bl vessel wall abn --- malignant hypertension, eclampsia, renal graft rejection, disseminated ca, cavernous hemangiomas, DIC. b- TTP --- wide spread platelet thrombi causing thrombocytopenia & HA c- HUS --- similar to TTP in children mainly causing uremia d- DIC --- inappropriate activation of coag factors with fibrin deposition in small bl v

23. 4. Toxic hemolysis * Infection – malaria, babesiosis, bartonellosis (direct RBC parasitism) -- Clostridium welchii (produce phospholipase causing hemolysis) * Snake & spider venom * Copper – Hemodialysis fluid, Wilson disease * Extensive burns * Liver cirrhosis – Spur cell anemia (acanthocytes) Abetalipoproteinemia – similar cells * Uremia – Burr cells, echinocytes

24. Paroxysmal nocturnal hemoglobinuria (PNH) Hemolytic disorder with intracorpuscular defect at stem cell level 3 manifestations- HA, venous th, deficient hematopoiesis (pancytopenia) Mech – Defect in DAF ( CD55) & MIRL (CD59) proteins causing RBC susceptible to lysis by complement.

25. Venous Th – abdominal veins (hepatic, portal, mesenteric) causing Budd-Chiari synd, congestive splenomegaly, abdominal pain. Cerebral veins & sinuses thrombosis Aplastic anemia 15-30%

26. Lab Ham's test (acidified serum lysis test) , sucrose lysis test, flow cytometry (CD55, 59) ℞ -- Bl T (washed RBCs), androgens, corticosteroids, heparin, ATG, & BMT

33. Basophilic stippling

34. G6PD Def

35. Retic

36. Budd-Chiari

37. HUS

38. malaria