Warm Autoimmune Hemolytic Anemia Lisa Rose-Jones, MD Monday, Aug 24th

Autoimmune Hemolytic Anemia: Warm Agglutinins Due to IgG antibodies that react with protein antigens on RBC body temperature Extravascular (red blood cells are destroyed in the spleen and other reticuloendothelial organs) hemolysis

Hemolysis Diagnosis: Typically find Hgb in range of g/dL (Hct 21-30%) Hemolysis: Increased Reticulocyte*/LDH/Indirect Bilirubin; Decreased Haptoglobin * Some w/ acute hemolysis may have reticulocytopenia from lag in marrow responsiveness 2/2 hemolytic stress

Warm Hemolysis Dx contd… Peripheral smear show spherocytosis (appear abnormally small and will lack the central pallor)

Direct Coombs’ test Test for dignosis of warm AIHA Adherent proteins are washed free from pt’s RBCs, mixed w/ antiserum or monocolonal Abs against different Immunoglobulins (IgG, C3d)= & if present on RBC surface degree agglutination quantitated by ELISA

Differential Diagnosis ~ Drug Induced: Cephalosporins, PCN & derivatives, NSAIDs, Quinidine ~Cold Agglutinins, (cold reacting IgM antibodies). Acral cynaosis

Pathogenesis of RBC destruction in AIHA: Immunoadherence: RBC (target cell) affixed to destructive cell (phagocyte) through immunoprotein molecule on each cell ~ ingestion may be partial, resulting in RBC w/ reduced surface:vol ratio = spherocyte, b/c reduced deformability many can’t cross splenic sinuses slits=destroyed

Why Autoantibody Production? B cell clones appear to be altered to produce these antibodies at high pathogenic titers Exacerbated by immune reaction of microbial infection?, viral infections (HIV, Mono) Rxn to blood transfusion or transplant my initiate this process

Why? Higher incidence of autoantibodies associated w/ Systemic Lupus 11% of patients’ w/ Chronic Lymphocytic Leukemia (CLL), likely b/c of again abnormal B cells (neoplastic proliferation)

Treatment Goals: ** Reduce the amount of Antibody being produced & reduce its effiency in destroying RBCs ~Success ≠ Cure, typically still evidence of persistent activity of underlying process. Control degree of anemia

Reduce Antibody Response 1)Corticosteroids (1mg/kg Prednisone), see response in 1-3 wks 2)Cytotoxic Agents: Azathioprine & Cyclophosphamide, given if lack response/inability tolerate #1. Response seen ~ 1 month. Case reports in resistant cases use of Cyclosporine, Mycophenolate, and anti-CD20 antibodies (Rituximab)

Reduce Antibody Effectiveness Splenectomy (removing primary site of destruction) IVIG: only occ effective (40%) in tx of AIHA refractory to conventional therapy w/ Prednisone & splenectomy (reducing the interaction b/w spleen macrophages & Ab coated RBCs)

RBC Transfusions: Tested for alloantibodies* (develops following pregnancy or prior transfusions) & autoantibodies Experience has indicated most pts will tolerate serologically incomplatible (atuoantibodies) blood

THE END!!