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

Warm Autoimmune Hemolytic Anemia

Lisa Rose-Jones, MDMonday, Aug 24th

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

THE END!!