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warm autoimmune hemolytic anemia

Etiology: 1) idiopathic 2) secondary (50%) a) lymphoproliferative disease - chronic lymphocytic leukemia (CLL) - non-Hodgkin's lymphoma - Hodgkin's disease (uncommon) b) connective tissue disease - systemic lupus erythematosus - scleroderma - rheumatoid arthritis c) immunodeficiency - HIV1 infection d) ulcerative colitis e) pharmaceutical agents - alpha-methyldopa (antibody to Rh antigen) - penicillin type (stable hapten) - cephalosporins [5] - quinidine type (unstable hapten) f) post viral infection g) non-lymphoproliferative neoplasms (rare) Epidemiology: - 70% of patients with autoimmune hemolytic anemia - median age of onset is 52 years - may occur at any age - slight female predominance Pathology: - IgG autoantibody binds to Rh antigen or Rh-like antigen - IgG antibodies bind complement (C3d) but more often facilitate Fc receptor mediated erythrocyte destruction by splenic macrophages Clinical manifestations: - rapid or insidious onset - anemia - dyspnea - fatigue - jaundice - splenomegaly - durable remission after initial therapy in 30% - chronic relapsing course nore common Laboratory: 1) complete blood count: anemia 2) reticulocyte count: reticulocytosis 3) peripheral blood smear: - spherocytosis - no schistocytes* 4) direct antiglobulin test (Coomb's test): - erythrocyte antibody is IgG - complement C3d in erythrocytes is negative or only weakly positive - optimal temperature for erythrocyte antibody binding is 37 C - IgG autoantibodies react with all reagent red cells from blood bank (panagglutinins), even when associated chronic lymphocytic leukemia [5] 5) serum chemistries - serum bilirublin: bilirubinemia - serum haptoglobin is low or absent - serum LDH is increased [1] * schistocytes on peripheral blood smear sufficient to rule out warm autoimmune hemolytic anemia without direct antiglobulin testing (DAT) [1] Complications: - venous thromboembolism (15-30%) [5] - pulmonary embolism, deep venous thrombosis Management: 1) withdrawal of offending agent(s) a) hemolysis general resolves with withdrawal of offending drug b) hemolysis may be prolonged after withdrawal of some offending drugs (i.e. fludarabine) [1] 2) glucocorticoid: prednisone 1-1.5 mg/kg/day a) most patients respond to therapy within 2-3 weeks b) hematocrit may normalize or stabilize in 30-90 days c) > 10-15 mg/day required to maintain acceptable blood hemoglobin 3) immunosuppressive agents if unresponsive to low-dose corticosteroids a) rituximab [1] b) azathioprine c) cyclophosphamide d) cyclosporine e) mycophenolate [5] 4) other agents for which anecdotal evidence exists a) danazol b) high-dose intravenous immune globulin 5) splenectomy if inadequate response to prednisone or immunosuppressants a) 50-70% of patients show marked improvement b) later relapse may occur 6) severely anemic patients may receive ABO & Rh type-specific blood transfusion even though all units may be incompatible (temporary benefit even with incompatible units)

General

autoimmune hemolytic anemia

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2022.
  2. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 666
  3. Packman CH. Hemolytic anemia due to warm autoantibodies. Blood Rev. 2008 Jan;22(1):17-31 PMID: 17904259
  4. Crowther M, Chan YL, Garbett IK, Lim W, Vickers MA, Crowther MA Evidence-based focused review of the treatment of idiopathic warm immune hemolytic anemia in adults. Blood. 2011 Oct 13;118(15):4036-40. PMID: 21778343
  5. Rothaus C NEJM Resident 360. Aug 14, 2019 https://resident360.nejm.org/clinical-pearls/autoimmune-hemolytic-anemia
  6. Sudulagunta SR, Kumbhat M, Sodalagunta MB et al. Warm autoimmune hemolytic anemia: clinical profile and management. J Hematol. 2017;6(1):12-20 PMID: 32300386 PMCID: PMC7155818 Free PMC article https://www.thejh.org/index.php/JH/article/view/303