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WITHIN THE RED CELL 1. Membrane defects - HS - HE - Hereditary pyropoikilocytosis - Hereditary stomatocytosis 2. Enzyme defects -G6PD -Pyruvate kinase.

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Presentation on theme: "WITHIN THE RED CELL 1. Membrane defects - HS - HE - Hereditary pyropoikilocytosis - Hereditary stomatocytosis 2. Enzyme defects -G6PD -Pyruvate kinase."— Presentation transcript:

1 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 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 AUTO-IMMUNE 1. Warm 2. Cold 3. Transfusion reactions 4. Drug associated OUTSIDE THE RED CELL HEMOLYTIC ANEMIA

2 HEMOLYTIC ANEMIA Intravascular Causes in Yellow 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 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 AUTO-IMMUNE 1. Warm 2. Cold 3. Transfusion reactions 4. Drug associated OUTSIDE THE RED CELL

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

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

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

6 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 < % SENS - 96% SPEC Classic Presentation

7 HEMOLYTIC ANEMIA 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 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 AUTO-IMMUNE 1. Warm 2. Cold 3. Transfusion reactions 4. Drug associated OUTSIDE THE RED CELL

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

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11 Hereditary Eliptocytosis -Autosomal Dominant -~1:4500 -Protein 4.1 -Dx: >75% elliptic RBC -Tx: Splenectomy

12 Hereditary Stomatocytosis -Autosomal Dominant -Lack of Protein 7.2 (stomatin) - Permeability to Na, K -Stomatocytes, xerocytes target cells -Tx: Splenectomy

13 Stateville Penitentiary, near Joliet, IL (mid 1950s)

14 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)

15 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

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

17 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

18 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

19 Liver disease: Spur Cell Anemia - cholesterol to phospholipid ratio -Splenic traffic jam -Clinically similar to TTP, no neuro manifestations -Limited Treatment

20 PNH -Somatic mut. on X-chromosome -Gene makes GPI anchor -Many proteins cant attach to RBC -No DAF and membrane inhibitor of reactive lysis (MIRL), RBC sensitive to complement -Hypercoaguable state -Dx: pancytopenia, LAP, sucrose hemolysis, Hams test (lysis in acidified serum) -Tx: Transfusion, glucocorticoids, Fe -BM transplant usually effective

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22 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

23 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)

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

26 Hematuria, Hemoglobinuria, and Myoglobinuria

27 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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