Autoimmune Hemolytic Anemia: Warm Agglutinins
• Due to IgG antibodies that react with protein antigens on RBC surface @ body temperature
• Extravascular (red blood cells are destroyed in the spleen and other reticuloendothelial organs) hemolysis
HemolysisDiagnosis:• Typically find Hgb in range of 7-10
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 Dxcontd…
• 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 Response1) Corticosteroids (1mg/kg Prednisone),
see response in 1-3 wks2) 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