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Haemolytic anaemia

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2. DEFINITION 1) Premature destruction of red cells and a shortened red cell life span below normal 120 days 2) Elevated erythropoietin levels and a compensatory increase in erythropoiesis 3) Accumulation of hemoglobin degradation products released by red cell breakdown derived from haemoglobin 3. CLASSIFICATION 4. ACQUIRED HAEMOLYTIC ANAEMIA IMMUNE HAEMOLYTIC ANAEMIA These can be subdivided into: a) Autoimmune b) Alloimmune c) Drug-induced 5. AUTOIMMUNE HAEMOLYTIC ANAEMIA warm antibodies bind to RBC most avidly at 370C cold antibodies bind best below 320C Caused by antibodies produced by patients own immune system Classified according to thermal properties of antibodies: 6. Warm AIHA: Antibody usually IgG, but may be IgM or IgA CAUSES 1. alternation in membrane surface antigen 2. Or abnormal response of B lymphocyte causing auto antibody formation May be primary or secondary autoimmune disorders, HIV, chronic lymphocytic leukaemia (CLL), non-Hodgkin's lymphoma (NHL) Most common type 7. Incidence: Occurs in either sex but female preponderance reported Occurs in all ages Higher incidence noted in patients > 45 years 8. Clinical Features: Hemolytic anaemia of varying severity Tends to remit and relapse Haemoglobinurea rare Jaundice Splenomegaly 9. Laboratory Features: Variable anaemia Blood film: polychromasia, microspherocytes Severe cases: nucleated RBCs, RBC fragments Mild neutrophilia, normal platelet count Evans syndrome: association with ITP Bone marrow: erythroid hyperplasia; underlying lymphoproliferative disorder Unconjugated hyperbilirubinaemia Haptoglobin levels low Urinary urobilinogen usually increased; haemoglobinuria uncommon 10. Serological Features Direct antiglobulin test (DAT; Coomb's test) usually positive Indirect antiglobulin test positive RBC may be coated with 1) IgG alone 2) IgG and complement 3) complement only Rarely anti-IgA and anti-IgM encountered 11. Treatment: Corticosteroids 1mg/kg daily till Hb stabilizes Transfusion Splenectomy: 1) patients who fail to respond to steroids Immunosuppressive Drugs : severe cases Others: 1) plasmapheresis 2) Intravenous immunoglobulin (IVIG) 1g/kg daily for 2days 3) danazol in chronic haemolytic anaemia 12. Cold AIHA: Two major types of cold antibody: 1) Cold agglutinins 2) Donath-Landsteiner antibodies Causes immediate intravascular destruction of sensitized RBCs by complement-mediated mechanisms or sequestration by liver (C3 coated RBCs preferentially removed here) 13. Cold Agglutinins: IgM autoantibodies that agglutinate RBCs optimally between 0 to 50C. Complement fixation occurs at higher temperatures Primary - Cold Haemagglutinin Disease (CHAD) or secondary (usually due to infections) Occurs in male mostly 14. Pathogenesis: Specificity usually against I/i antigens Bind red cells in peripheral circulation impeding capillary flow, producing acrocyanosis 15. Clinical Features: Chronic haemolysis; episodes of acute haemolysis can occur on chilling Acrocyanosis frequent; skin ulceration and necrosis uncommon Mild jaundice and splenomegaly Secondary cases e.g. Mycoplasma, self- limited 16. Laboratory Features: Anaemia- mild to moderate Blood film: a) agglutination, or rouleax b) spherocytosis less marked than warm AIHA DAT +ve: complement only Anti-I: idiopathic disease, mycoplasma, some lymphomas Anti-i: infectious mononucleosis, lymphomas 17. Treatment: Keep patient warm Treat underlying cause Alkylating agents: chlorambucil Splenectomy and steroids generally not helpful Plasmapheresis- temporary relief Transfusion- washed packed cells in severe cases 18. Paroxysmal Cold Haemoglobinuria Rare form Characterized by recurrent haemolysis following exposure to cold common due to association with syphilis Antibodies usually IgG with specificity for P antigen Biphasic: a) binds to red cells at low temperatures, b) lysis with complement occurs at 37C 19. Drug-induced Haemolytic Anaemia May cause immune haemolytic anaemia by three different mechanisms: Neoantigen type e.g. Quinidine immune complex mechanism Autoimmune mechanism e.g. - Methyldopa Drug adsorption mechanism e.g. Penicillin Hapten mechanism 20. Non-immune haemolytic anaemias: Paroxysmal nocturnal haemoglobinuria (PNH) Red cell fragmentation syndromes March haemoglobinuria Infections Chemical and physical agents Secondary haemolytic anaemia 21. Paroxysmal nocturnal haemoglobinuria (PNH) Acquired haemopoietic stem cell disorder Characterized by increased sensitivity of red cells to haemolysis by complement 22. Pathogenesis: Arise as a clonal abnormality of stem cells Disorder a consequence of somatic mutations in synthesis of the glycosylphosphatidylinositol (GPI) anchor Results in deficiencies of several GPI- anchored membrane proteins 1) decay accelerating factor (DAF), 2) membrane inhibitor of reactive lysis (MIRL), 3) acetylcholine esterase, 4) leukocyte alkaline phosphatase (LAP) These proteins involved in complement degradation 23. Clinical Features: Haemoglobinuria occurs intermittently Nocturnal haemoglobinuria uncommon Chronic haemolytic anaemia which may be severe Iron deficiency due to loss in urine Bleeding may occur secondary to thrombocytopenia Thrombosis a prominent feature 24. Laboratory Features: Pancytopenia Anaemia may be severe Macrocytosis may be present due to mild reticulocytosis Hypochromic, microcytic due to iron deficiency Marrow: erythroid hyperplasia; may be aplastic Urine: haemosiderinuria constant feature 25. Treatment: Transfusion Oral iron Folate supplements Steroids may be of benefit Anticoagulation for thrombotic complications 26. Red Cell Fragmentation Syndromes Microangiopathic haemolytic anaemia (MAHA) Intravascular haemolysis Red cells adhere to fibrin and are fragmented by force of blood flow in abnormal arterioles. Underlying disorders: adenocarcinomas Complications of pregnancy: a) Preeclampsia, eclampsia, Haemolysis, Elevated Liver enzymes, Low Platelets (HELLP) Disseminated Intravascular Coagulation (DIC) Thrombotic Thrombocytopenic Purpura (TTP)/ Haemolytic Uraemic Syndrome (HUS) Malignant hypertension 27. Laboratory Findings: Blood film: 1) schistocytes prominent, 2) spherocytes, 3) reticulocytes, 4) normoblasts Thrombocytopenia Coagulopathy in DIC 28. Traumatic cardiac haemolytic anaemia Seen in patients with 1) prosthetic heart valves, 2) cardiac valvular disorders esp. severe aortic stenosis Due to 1) physical damage of red cells from turbulence 2) high shear stresses Anaemia usually mild

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