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  • • Fatigue, pallor, jaundice

    • Splenomegaly

    • Persistent anemia and reticulocytosis


  • • Autoimmune disorder that is either idiopathic (40-50%) or secondary to drug exposure, connective tissue diseases, or lymphoproliferative disorders

    • Classified according to the optimal temperature at which autoantibodies react with the red cell surface (warm or cold antibodies)

    • -Warm antibody: IgG autoantibodies directed against the Rh locus on the erythrocyte coat the cell and bind to IgG specific Fc receptors on macrophages in the spleen

      -Cold antibody: IgM autoantibodies are directed against the I red cell antigen; hemolysis occurs intravascularly and not within the spleen

    • Most common after age 50; occurs twice as often in women than in men

Symptoms and Signs

  • • Fatigue

    • Mild jaundice

    • Fever

    • Splenomegaly

Laboratory Findings

  • • Acute onset normocytic normochromic anemia

    • Reticulocytosis (> 10%)

    • Erythroid hyperplasia of the marrow

    • Elevation of serum indirect bilirubin

    • Serum haptoglobin is usually low or absent

    • Positive direct Coombs test

  • • Rarely, a sudden, severe onset hemolytic anemia produces hemoglobinuria, renal tubular necrosis, and a 40-50% death rate

    • May be associated with systemic lupus erythematosus and chronic lymphocytic leukemia

    • Drugs commonly implicated include methyldopa, penicillin, quinidine

Rule Out

  • • Other causes of hemolytic anemia

    • -Hereditary hemolytic anemias

      -Thrombotic thrombocytopenic purpura

      -Disseminated intravascular coagulation


  • • CBC count

    • Serum bilirubin

    • Reticulocyte count

    • Peripheral blood smear

    • Serum haptoglobin

    • Bone marrow biopsy

    • Coombs test

When to Admit

  • • Severe anemia

When to Refer

  • • All cases should be managed in conjunction with a hematologist

  • • Drug-induced hemolytic anemia: Terminate exposure to the agent.


  • • Splenectomy is indicated for patients with warm-antibody hemolysis meeting the following criteria:


  • • Failure to respond to 4-6 weeks of high-dose corticosteroid therapy

    • Relapse when corticosteroids are withdrawn

    • Contraindications to corticosteroid therapy

    • Chronic high-dose corticosteroid therapy


  • • Cold-antibody hemolytic anemia


  • • Corticosteroids

    • IV immune globulin

Treatment Monitoring

  • • CBC count


  • • Pigment gallstones


  • • 75% remission rate with medical treatment; 25% are permanent

    • Relapses may occur after splenectomy


Beutler E et al. Hemolytic anemia. Semin Hematol. 1999;36:38.  [PubMed: 10595753]

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