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WITHIN THE RED CELL 1. Membrane defects - HS - HE

Learn about causes, symptoms, and treatment of hemolytic anemia including membrane defects, enzyme defects, autoimmune and non-immune factors, intravascular and extravascular hemolysis, and related disorders.

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WITHIN THE RED CELL 1. Membrane defects - HS - HE

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  1. HEMOLYTIC ANEMIA OUTSIDE THE RED CELL WITHIN THE RED CELL 1. Membrane defects - HS - HE - Hereditary pyropoikilocytosis - Hereditary stomatocytosis 2. Enzyme defects -G6PD -Pyruvate kinase 3. Hemoglobin defects - SCA - Thalassemias - Unstable hemoglobin AUTO-IMMUNE 1. Warm 2. Cold 3. Transfusion reactions 4. Drug associated NON-IMMUNE 1. Hypersplenism 2. Fragmentation syndromes - grafts / valves / AS - HTN / Pre-eclampsia - March hemoglobinuria - MAHA - TTP/HUS - DIC - hemangioma 2. Infections/Toxins (Malaria, Babeosis, Bartonella, Clostridium welchii, snakes, spiders) 3. Drugs 4. Liver dz (Spur cell) 5. PNH

  2. HEMOLYTIC ANEMIAIntravascular Causes in Yellow OUTSIDE THE RED CELL WITHIN THE RED CELL 1. Membrane defects - HS - HE - Hereditary pyropoikilocytosis - Hereditary stomatocytosis 2. Enzyme defects -G6PD -Pyruvate kinase 3. Hemoglobin defects - SCA - Thalassemias - Unstable hemoglobin AUTO-IMMUNE 1. Warm 2. Cold 3. Transfusion reactions 4. Drug associated NON-IMMUNE 1. Hypersplenism 2. Fragmentation syndromes - grafts / valves / AS - HTN / Pre-eclampsia - March hemoglobinuria - MAHA - TTP/HUS - DIC - hemangioma 2. Infections/Toxins (Malaria, Babeosis, Bartonella, Clostridium welchii, snakes, spiders) 3. Drugs 4. Liver dz (Spur cell) 5. PNH

  3. Alf Alving, Scientist, U.S. Army(mid 1950s)

  4. RBC RES HBG Extravascular Hemolysis Fe Transferrin Storage and recycled in marrow CO Lung Biliverdin Uncojugated bilirubin Conjugation Bile

  5. Intravascular Hemolysis RBC LYSIS HBG HAPTOGLOBIN REMOVED BY LIVER HBG TAKEN UP BY RENAL TUBULAR CELLS HEMOSIDERIN CELLS SLOUGHED IN URINE 1 WEEK LATER HEMOGLOBINEMIA HEMOGLOBINURIA

  6. Classic Presentation 1. New onset pallor and anemia 2. Splenomegaly 3. Jaundice 3.  Indirect bilirubin (<5) 4.  Reticulocyte percentage 5.  LDH (esp LDH-2) 6.  RBC life span 7.  Haptoglobin < 25 - 83% SENS - 96% SPEC

  7. HEMOLYTIC ANEMIA OUTSIDE THE RED CELL WITHIN THE RED CELL 1. Membrane defects - HS - HE - Hereditary pyropoikilocytosis - Hereditary stomatocytosis 2. Enzyme defects -G6PD -Pyruvate kinase 3. Hemoglobin defects - SCA - Thalassemias - Unstable hemoglobin AUTO-IMMUNE 1. Warm 2. Cold 3. Transfusion reactions 4. Drug associated NON-IMMUNE 1. Hypersplenism 2. Fragmentation syndromes - grafts / valves / AS - HTN / Pre-eclampsia - March hemoglobinuria - MAHA - TTP/HUS - DIC - hemangioma 2. Infections/Toxins (Malaria, Babeosis, Bartonella, Clostridium welchii, snakes, spiders) 3. Drugs 4. Liver dz (Spur cell) 5. PNH

  8. Hereditary Spherocytosis • Autosomal Dominant • ~1:3000 • Spectrin, Ankyrin, Protein 3 • Dx: osmotic frag., neg. direct Coombs • Tx: Splenectomy, cholecystectomy, vaccine, folate

  9. Hereditary Eliptocytosis • Autosomal Dominant • ~1:4500 • Protein 4.1 • Dx: >75% elliptic RBC • Tx: Splenectomy

  10. Hereditary Stomatocytosis • Autosomal Dominant • Lack of Protein 7.2 (stomatin) •  Permeability to Na, K • Stomatocytes, xerocytes  target cells • Tx: Splenectomy

  11. Stateville Penitentiary, near Joliet, IL (mid 1950s)

  12. Warm Immunohemolyis • Most common in adult women (CT, SLE) • IgG bound to RBC activate phagocytes and complement • Dx: + direct Coombs • Tx: • 1. Prednisone 1mg/kg ( RES, Ab production) • 2. Splenectomy • 3. Cyclophosphamide • 4. Azathioprine • 5. IV gamma globulin • 6. Transfusions (cross-matching impossible)

  13. Cold Immunohemolyis • monoclonal production of cold agglutinins • response to infection (M. pneumoniae, EBV) • IgM mediated complement attack (no Fc) • Tx: • 1. Underlying cause • 2. Splenectomy, Steroids, have minimal role

  14. 1931 – Nobel prize for discovery of hexose-monophosphate shunt and glycolytic pathway (Otto Meyerhof, Gustav Embden students) • 1931-1944 discovery of cytochromes, flavin adenine dinucleotide, nicotinamide adenine dinucleotide. • 1944 – offered 2nd Nobel prize, but prevented from accepting it by Hitler Otto Warburg (1883-1970)

  15. TTP • Ab inhibits protease that normally cleaves vWF • 1. Intravascular hemolysis • 2. Thrombocytopenia • 3. Non focal neurologic findings • 4.  Renal function • 5. Fever • Dx • Negative direct Coombs • Fragmented RBC, but no spherocytes • Normal coagulation tests • Tx • Plasmapheresis, glucocorticoids, dipyridamole, dextran, ASA

  16. HUS • O157:H7 Shiga-like verotoxins that damage renal vascular endothelial cells • Clinically similar to TTP, no neuro manifestations • Tx • Plasmapheresis, dialysis, transfusions • Role of glucocorticoids, dextran, heparin uncertain

  17. Liver disease: Spur Cell Anemia •  cholesterol to phospholipid ratio • Splenic traffic jam • Clinically similar to TTP, no neuro manifestations • Limited Treatment

  18. PNH • Somatic mut. on X-chromosome • Gene makes GPI anchor • Many proteins can’t attach to RBC • No DAF and membrane inhibitor of reactive lysis (MIRL), RBC sensitive to complement • Hypercoaguable state • Dx: pancytopenia,  LAP, sucrose hemolysis, Ham’s test (lysis in acidified serum) • Tx: Transfusion, glucocorticoids, Fe • BM transplant usually effective

  19. G6PD • X chromosome, recessive • 11% African American males •  sensitivity to oxidative stress • Heinz bodies, bite cells • Triggers: infection, drugs, met. acidosis, moth balls, fava beans • Dx: enzyme assay (fluorescent spot) after acute episode • Tx: avoid triggers

  20. DRUGS THAT CAUSE HEMOLYTIC ANEMIA OXIDANT 1. Antibiotics - nitrofurantoin - sulfa - dapsone - nalidixic acid 2. Primaquine 3. Pyridium 4. Doxorubicin 5. Methylene blue PENICILLIN TYPE (Ab + Drug-Membrane) 1. Penicillins 2. Cephalosporins 3. Synthetic penicillins IMMUNE COMPLEX (Ab-Drug + Membrane) (Most common type) 1. quinidine 2. rifampin AUTOIMMUNE (AutoAb to Rh Ag) 1. methyldopa MISCELLANEOUS 1. Vitamin K (water soluble)

  21. Cinchona plant, Costa Rica, containing both quinine and quinidine, named for the Countess of the Spanish town of Chinchon

  22. Hematuria, Hemoglobinuria, and Myoglobinuria

  23. Causes of Intravascular Hemolysis 1. Transfusion reactions 2. Infections - Clostridium welchi - Malaria, Babeosis - Bartonella - Mycoplasma pneumonia 3. Fragmentation syndromes - grafts / valves / AS - HTN / Pre-eclampsia - March hemoglobinuria - TTP/HUS - DIC - hemangioma 4. G6PD deficiency with oxidant stress 5. PNH 6. Infusion of hypotonic solutions 7. Snake and Spider venoms 8. Some autoimmune hemolytic anemias (RhoD)

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