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Published byJacob McCracken Modified over 11 years ago
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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
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HEMOLYTIC ANEMIA Intravascular 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
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Alf Alving, Scientist, U.S. Army (mid 1950s)
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Extravascular Hemolysis
RBC RES HBG Extravascular Hemolysis Fe Transferrin Storage and recycled in marrow CO Lung Biliverdin Uncojugated bilirubin Conjugation Bile
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HBG TAKEN UP BY RENAL TUBULAR CELLS
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
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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
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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
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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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Hereditary Eliptocytosis
Autosomal Dominant ~1:4500 Protein 4.1 Dx: >75% elliptic RBC Tx: Splenectomy
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Hereditary Stomatocytosis
Autosomal Dominant Lack of Protein 7.2 (stomatin) Permeability to Na, K Stomatocytes, xerocytes target cells Tx: Splenectomy
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Stateville Penitentiary, near Joliet, IL (mid 1950s)
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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)
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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
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1931 – 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. 1944 – offered 2nd Nobel prize, but prevented from accepting it by Hitler Otto Warburg ( )
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TTP Ab inhibits protease that normally cleaves vWF Dx Tx
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
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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
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Liver disease: Spur Cell Anemia
cholesterol to phospholipid ratio Splenic traffic jam Clinically similar to TTP, no neuro manifestations Limited Treatment
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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
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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
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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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Cinchona plant, Costa Rica, containing both quinine and quinidine, named for the Countess of the Spanish town of Chinchon
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Hematuria, Hemoglobinuria, and Myoglobinuria
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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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