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HEMOLYTIC ANEMIAS

HEMOLYTIC ANEMIAS. increase red cell destruction = reduced red- cell life span. HEMOLYTIC ANEMIAS. A red blood cell survives 90 to 120 days in the circulation ; about 1% of human red blood cells break down each day

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HEMOLYTIC ANEMIAS

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  1. HEMOLYTIC ANEMIAS increase red celldestruction = reduced red-cell life span

  2. HEMOLYTIC ANEMIAS • A red blood cell survives 90 to 120 days in the circulation;about 1% of human red blood cells break down each day • The spleen is the main organ which removes old and damaged RBCs from the circulation

  3. Mechanisms of hemolysis • Extravascular • red cellsdestructionoccurs in reticuloendothelial system • Intravascular • red cellsdestructionoccurs in vascularspace

  4. Signs of hemolytic anemias • Symptoms of anemia – pallor, fatique, rapid pulse • Jaundice • Splenomegaly

  5. Diagnosis of hemolyticanemias • Anemia • Reticulocytosis • Indirecthyperbilirubinemia • Increasedlevel of lactate dehydrogenase (LDH) • Absenceorreduced of free serum haptoglobin

  6. INtravascularhemolysis • laboratorysigns of intravascularhemolysis: - tests for hemolysis and aditionally: - hemoglobinemia - hemoglobinuria - hemosiderynuria

  7. hemolyticanemias Compensated hemolysis – increase erythropoesis compensates increase destruction of erythrocytes Decompensated hemolysis - erythropoesis can not compensates increae destruction – patient needs therapy

  8. Complications of increased, chronichemolysis • Folinic acid deficiency • Gallstones • Thrombosis • Hemolytic crisis - rapid destruction of large numbers of red blood cells

  9. Classification of hemolyticanemias • Hereditary • Membranedefect (spherocytosis, elliptocytosis) • Metabolicdefect (Glucoze-6-Phosphate-Dehydrogenaze (G6PD) deficiency, Pyruvatekinase (PK) deficiency) • Hemoglobinopathies (thalassemias, sicklecell anemia ) • Acquired • Immunehemolyticanemias • Nonimmunehemolyticanemias

  10. Hereditary membrane defects • Spherocytosis • The most commondefect of red cellmembrane protein (1/2000 birth) • Inheritance - autosomaldominant • Deficient of membrane protein causeschange of shape (round, no central pallor) • Clinicalfeatures: jaundice, gallstones, splenomegaly, constitutional skeleton changes (ietowercranium, gothicpalate) • Laboratoryfeatures: anemia, hiperbilirubinemia, retikulocytosis,  LDH - bloodsmear - microspherocytes - abnormalosmoticfragilitytest • Treatment - splenectomy

  11. Spherocytes

  12. Hereditarymembranedefects • Elliptocytosis

  13. Hereditary metabolic defect • Glucoze-6-Phosphate-Dehydrogenaze (G6PD) deficiency • Hemolysisisinduce by infections, drugs • Hemolysisisintravascular • Pyruvatekinase (PK) deficiency

  14. HereditaryHemoglobinopathies • Thalassemias • Alfa thalassemia • Beta thalasemia: major, minor (trait), intermedia • Delta/Beta thalassemia • Hereditarypersistentce of fetal hemoglobin • Sicklecell anemia

  15. SICKLE CELL ANEMIADefinition: chronichemolytic anemia characterized by sickle-shaped red cellscaused by homozygousinheritance of Hemoglobin S

  16. SICKLE CELL ANEMIA - incidence - Occurs mainly in people of African, Caribbean, Mediterranean descent - Homozygous - about 0,3% of Arficans Americans in the USA (have sickle cell anemia) Hetezygotes-8-13% of Africans Americans (are not anemic, but the sickling trait = sicklemia can be demonstrated in vitro)

  17. SICKLE CELL ANEMIA-pathogenesis - 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

  18. SICKLE CELL ANEMIA - clinicalfeatures IN HOMOZYGOTES Onset in the first or second year of live Period episodes of acute vascular occlussion (painful crisis) 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 Events which impair tissue oxygenation can precipitate crisis (f.e. pneumonia)

  19. SICKLE CELL ANEMIA-therapy Preventive measures: prevention or remedy of: infections (penicillin prophylaxis and pneumococcal vaccination), fever, dehydratation,acidosis, hypoxemia, cold exposure Blood transfusions for very severe anemia New approaches to therapy; 1. Activation of Hb F synthesis - 5-azacytidine 2. Antisickling agents acting on hemoglobin or membrane 3. Bone marrow transplantation

  20. 2. Acquired A. Immunehemolyticanemias 1. Autoimmunehemolytic anemia - caused by warm-reactiveantibodies - caused by cold-reactiveantibodies 2. Alloimmunehemolytic anemia (transfusion of incompatibleblood) B. Nonimmunehemolyticanemias 1. Chemicals 2. Bacterialinfections, parasiticinfections (malaria) 3. Hemolysisdue to physical trauma (e.g. microangiopathichemolytic anemia) 4. Hypersplenism 5. Paroxysmalnocturnal hemoglobinuria (PNH)

  21. Autoimmunehemolytic anemia - AIHA • caused by warm-reactiveantibodies (70%) - infections, connectivetissuedisorders, drugs • caused by cold-reactiveantibodies (30%) – in temp. < 37 (4°) - infections, CLL, NHL Laboratoryfindings: directCoombs test(directantiglobulin test) Treatment: underlyingdisease, steroids, immunosupresive Avoid RBC transfusions

  22. 2. Acquired • Immunehemolyticanemias 1. Autoimmunehemolytic anemia - caused by warm-reactiveantibodies - caused by cold-reactiveantibodies 2. Alloimmunehemolytic anemiaB. Nonimmunehemolyticanemias 1. Chemicals 2. Bacterialinfections, parasiticinfections (malaria) 3. Hemolysisdue to physical trauma (e.g. microangiopathichemolytic anemia) 4. Hypersplenism 5. Paroxysmalnocturnal hemoglobinuria (PNH)

  23. Alloimmunehemolytic anemia • Transfusion of incompatibleblood • Serologicincompatibility • Aftertransplantation of bonemarrowororgans

  24. 2. Acquired • Immunehemolyticanemias 1. Autoimmunehemolytic anemia - caused by warm-reactiveantibodies - caused by cold-reactiveantibodies 2. Alloimmunehemolytic anemiaB. Nonimmunehemolyticanemias 1. Chemicals 2. Bacterialinfections, parasiticinfections (malaria) 3. Hemolysisdue to physical trauma - microangiopathichemolytic anemia 4. Hypersplenism 5. Paroxysmalnocturnal hemoglobinuria (PNH)

  25. Classificationof microangiopathichemolytic anemia • Thromboticthrombocytopenic purpura (TTP) • Hemolyticuremicsyndrome (HUS)

  26. Microangiopathichemolytic anemia • Intravascular hemolysis caused by fragmentation of normal red cells passing through abnormal arterioles • Arterioles are changed by deposition of platelets and fibrin • Microvascular lesion cause organ demage (kidney, CNS)

  27. Microangiopathichemolyticanaemia Underlying disease • Invasive carcinoma • Complication of pregnancy • Serious infection • Drugs

  28. Microangiopathichemolyticanaemia • Symptoms: • Related to the primary disease • Related to organs demage • Laboratory findings • Blood film: schistocytes

  29. 2. Acquired • Immunehemolyticanemias 1. Autoimmunehemolytic anemia - caused by warm-reactiveantibodies - caused by cold-reactiveantibodies 2. Transfusion of incompatiblebloodB. Nonimmunehemolyticanemias 1. Chemicals 2. Bacterialinfections, parasiticinfections (malaria) 3. Hemolysisdue to physical trauma - hemolytic - uremicsyndrome (HUS) - thromboticthrombocytopenic purpura (TTP) - prostheticheartvalves 4. Hypersplenism 5. Paroxysmalnocturnal hemoglobinuria (PNH)

  30. Hypersplenism • State of hyperactivity of the spleen • Causes of hypersplenism • Infection – bacterial, viruses, fungi • Inflammatory diseases - • Neoplasm • Storage disorders (Gaucher disease) • Other – amyloidosis, sarcoidosis

  31. 2. Acquired • Immunehemolyticanemias 1. Autoimmunehemolytic anemia - caused by warm-reactiveantibodies - caused by cold-reactiveantibodies 2. Transfusion of incompatiblebloodB. Nonimmunehemolyticanemias 1. Chemicals 2. Bacterialinfections, parasiticinfections (malaria) 3. Hemolysisdue to physical trauma - hemolytic - uremicsyndrome (HUS) - thromboticthrombocytopenic purpura (TTP) - prostheticheartvalves 4. Hypersplenism 5. Paroxysmalnocturnal hemoglobinuria (PNH)

  32. Pathogenesis- anacquiredclonaldisease, arising from a somaticmutation in a single abnormalstemcell- deficiency of the GPI (glycosyl-phosphatidyl-inositol) anchor on the surface of hematopoieticcells- red cellsaremoresensitive to the lyticeffect of complement- intravascularhemolysis Paroxysmal nocturnal hemoglobinuria (PNH)

  33. Paroxysmalnocturnal hemoglobinuria (PNH) Symptoms • Irregularly hemoglobinuria occurs with darkbrownurine in the morning • Hemolysisisreleased by infection, surgeryorotherevents • Increasedrisk of thrombosis • Renalfailure • Neurologicmanifestation - headaches

  34. Laboratoryfeatures- hemoglobinuria - hemosiderinuria - pancytopenia - chronicurinary iron loss - serum iron concentrationdecreased - positiveHam’s test (acidhemolysis test) - specificimmunophenotype of erytrocytes (CD59, CD55) Paroxysmalnocturnal hemoglobinuria (PNH)

  35. Treatment- washed RBC transfusion - iron therapy - allogenicbonemarrowtransplantationMonoclonalantibodyEculizumab(trade name Soliris) Paroxysmalnocturnal hemoglobinuria (PNH)

  36. What do youhave to remember Anemia + • Retikulocytosis •  bilirubin (unconjugated),  LDH •  haptoglobin • Haemoglobin and haemosiderin in urine

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