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  1. 1. HEMOLYTIC ANEMIASred-cell life span
  2. 2. Classification of Hemolytic anemiasI. Red cell abnormality (Intracorpuscular factors) A. Hereditary 1. Membrane defect (spherocytosis, elliptocytosis) 2. Metabolic defect (Glucoze-6-Phosphate-Dehydrogenaze (G6PD) deficiency, Pyruvate kinase (PK) deficiency) 3. Hemoglobinopathies (unstable hemoglobins, thalassemias, sickle cell anemia )B. Acquired 1. Membrane abnormality-paroxysmal nocturnal hemoglobinuria (PNH)
  3. 3. II. Extracorpuscular factorsA. Immune hemolytic anemias 1. Autoimmune hemolytic anemia - caused by warm-reactive antibodies - caused by cold-reactive antibodies 2. Transfusion of incompatible bloodB. Nonimmune hemolytic anemias 1. Chemicals 2. Bacterial infections, parasitic infections (malaria), venons 3. Hemolysis due to physical trauma - hemolytic - uremic syndrome (HUS) - thrombotic thrombocytopenic purpura (TTP) - prosthetic heart valves 4. Hypersplenism
  4. 4. Mechanisms of hemolysis: - intravascular - extravascular
  5. 5. Inravascular hemolysis (1):- red cells destruction occurs in vascular space- clinical states associated with Intravascular hemolysis: acute hemolytic transfusion reactions severe and extensive burns paroxysmal nocturnal hemoglobinuria severe microangiopathic hemolysis physical trauma bacterial infections and parasitic infections (sepsis)
  6. 6. Inravascular hemolysis (2):- laboratory signs of intravascular hemolysis: indirect hyperbilirubinemia erythroid hyperplasia hemoglobinemia methemoalbuminemia hemoglobinuria absence or reduced of free serum haptoglobin hemosiderynuria
  7. 7. Extravascular hemolysis :- red cells destruction occurs in reticuloendothelial system- clinical states associated with extravascular hemolysis : autoimmune hemolysis delayed hemolytic transfusion reactions hemoglobinopathies hereditary spherocytosis hypersplenism hemolysis with liver disease- laboratory signs of extravascular hemolysis: indirect hyperbilirubinemia increased excretion of bilirubin by bile erythroid hyperplasia hemosiderosis
  8. 8. Hemolytic anemia - clinical features: - pallor - jaundice - splenomegaly
  9. 9. Laboratory features:1. Laboratory features - normocytic/macrocytic, hyperchromic anemia - reticulocytosis - increased serum iron - antiglobulin Coombs’ test is positive2. Blood smear - anisopoikilocytosis, spherocytes - erythroblasts - schistocytes3. Bone marrow smear - erythroid hyperplasia
  10. 10. Diagnosis of hemolytic syndrome: 1. Anemia 2. Reticulocytosis 3. Indirect hyperbilirubinemia
  11. 11. Autoimmune hemolytic anemia caused by warm-reactive antibodies: I. Primary II. Secondary 1. acute - viral infections - drugs ( α -Methyldopa, Penicillin, Quinine, Quinidine) 2. chronic - rheumatoid arthritis, systemic lupus erythematosus - lymphoproliferative disorders (chronic lymphocytic leukemia, lymphomas, WaldenstrÖm’s macroglobulinemia) - miscellaneous (thyroid disease, malignancy )
  12. 12. Autoimmune hemolytic anemia caused by cold-reactive antibodies: I. Primary cold agglutinin disease II. Secondary hemolysis: - mycoplasma infections - viral infections - lymphoproliferative disorders III. Paroxysmal cold hemoglobinuria
  13. 13. Autoimmune hemolytic anemia - diagnosis - positive Coombs’ testTreatment: - steroids - splenectomy - immunosupressive agents - transfusion
  14. 14. Hereditary microspherocytosis1. Pathophysiology - red cell membrane protein defects (spectrin deficiency) resulting cytoskeleton instability2. Familly history3. Clinical features - splenomegaly4. Laboratory features - hemolytic anemia - blood smear-microspherocytes - abnormal osmotic fragility test - positive autohemolysis test - prevention of increased autohemolysis by including glucose in incubation medium5. Treatment - splenectomy
  15. 15. Paroxysmal nocturnal hemoglobinuria1. Pathogenesis - an acquired clonal disease, arising from a somatic mutation in a single abnormal stem cell - glycosyl-phosphatidyl- inositol (GPI) anchor abnormality - deficiency of the GPI anchored membrane proteins (decay-accelerating factor =CD55 and a membrane inhibitor of reactive lysis =CD59) - red cells are more sensitive to the lytic effect of complement - intravascular hemolysis2. Symptoms - passage of dark brown urine in the morning
  16. 16. 3. PNH –laboratory features: - pancytopenia - chronic urinary iron loss - serum iron concentration decreased - hemoglobinuria - hemosiderinuria - positive Ham’s test (acid hemolysis test) - positive sugar-water test - specific immunophenotype of erytrocytes (CD59, CD55)4. Treatment: - washed RBC transfusion - iron therapy - allogenic bone marrow transplantation
  17. 17. SICKLE CELL ANEMIADefinition: chronic hemolytic anemia occuring almost exclusively in blacks and characterized by sickle-shaped red cells(RBCs) caused by homozygous inheritance of Hemoglobin S
  18. 18. SICKLE CELL ANEMIA-pathogenesis- In Hb S, valine is substituted for glutamic acid in the sixth amino acid of the ß chain.- Deoxy-Hb S is much less soluble than deoxy Hb A; it forms a gelatinous network of fibrous polymersthat cause RBCs to sickle at sites of low pO2.- Hemolysis-because sickle RBCs are too fragile to withstand the mechanical trauma of circulation- Occlusion in microvascular circulation caused by distorted, inflexible RBCs adhering to vascular endothelium
  19. 19. SICKLE CELL ANEMIA-incidence- Homozygous - about 0,3% of blacks in the USA (have sickle cell anemia)- Hetezygotes-8-13% of blacks, (are not anemic, but the sickling trait=sicklemia can be demonstrated in vitro)
  20. 20. SICKLE CELL ANEMIA-clinical featuresIN HOMOZYGOTES1. Clinical complications due to severe hemolytic anaemia - slowed growth and development in children - bilirubins stones - aplastic crisis - congestive heart failure from chronic anemias and cardiac overload compensation2. Consequences of vaso-occlusion of the microcirculations (tissue ischemia and infarction) - infarction of spleen, brain, marrow, kidney, lung, aseptic necrosis, central nervous system and ophtalmic vascular lesions
  21. 21. SICKLE CELL ANEMIA-laboratory findinges1. Anemia-normocytic or slightly macrocytic2. Leukocytosis(chronic neutrophilia)3. Thrombocytosis-usually mild<1000G/l4. Reticulocytosis5. Peripheral smear: sickle shaped red cells, polychromatophilia, Howell-Jolly bodies6. Hb -electrophoresis
  22. 22. SICKLE CELL ANEMIA-therapyPreventive measures:prevention or remedy of: infections(penicillin prophylaxis and pneumococcal vaccination), fever, dehydratation,acidosis, hypoxemia, cold exposureBlood transfusions for very severe anemiaNew approaches to therapy; 1. Activation of Hb F synthesis -5-azacytidine 2. Antisickling agents acting on hemoglobin or membrane 3. Bone marrow transplantation