Autoimmune Hemolytic Anemia



  • Autoimmune hemolytic anemia (AIHA) is characterized by shortened red cell survival caused by autoantibodies directed against RBC surface antigens, with or without the participation of complement on the red cell membrane.
  • Natural history
    • Acute disease
      • Onset with rapid fall in hemoglobin level over hours to days
      • Usual course: complete resolution of disease within 3 to 6 months
      • Resolution more likely in children who present between 2 and 12 years of age
    • Chronic disease
      • Slower onset of anemia over weeks to months, with some having persistence of hemolysis or intermittent relapses
      • More likely to be associated with underlying chronic illness
      • More common in adults and children <2 years or >12 years of age


  • Less common in children and adolescents than in adults
  • No apparent racial or sexual predisposition (in childhood)


  • ~1 to 3:100,000 persons/year
  • Peak incidence in childhood is in first 4 years of life with most cases due to warm AIHA.


  • Warm autoantibodies (~80% cases)
    • Maximal activity of in vitro antibody RBC binding at 37°C
    • IgG-class antibody usually
    • IgG-coated RBCs cleared, predominantly extravascularly in the spleen, by macrophages
  • Cold autoantibodies (cold agglutinins) (7–25%)
    • Maximal activity of in vitro RBC binding at temperatures between 0°C and 30°C
    • Almost always caused by IgM antibody with specificity for antigens of the i/I system on RBCs
    • Anti-I antibodies characteristic of Mycoplasma pneumoniae—associated hemolysis and can be associated with infectious mononucleosis
    • Hemolysis is complement-dependent.
  • Paroxysmal cold hemoglobinuria
    • IgG autoantibody binds RBC at cooler areas of the body (i.e., extremities), causing irreversible binding of complement components (C3 and C4). When coated RBCs enter warmer areas of the body, IgG falls off and complement causes hemolysis (Donath–Landsteiner biphasic hemolysin).
    • Unusual IgG antibody with anti-P specificity
    • Most frequently found in children with viral infections (30%)


  • Idiopathic
  • Passive transfer of maternal antibodies
  • Secondary to an underlying disorder
    • Infection: viral (e.g., Epstein-Barr virus, cytomegalovirus, hepatitis, HIV) or bacterial (e.g., Mycoplasma, Streptococcus, typhoid fever, Escherichia coli septicemia)
    • Drugs: antimalarials, antipyretics, sulfonamides, penicillin, ceftriaxone, rifampin
    • Hematologic disorders: leukemia, lymphoma
    • Autoimmune disorders: lupus, mixed connective tissue disorders, Wiskott-Aldrich syndrome, ulcerative colitis, rheumatoid arthritis, common variable immunodeficiency, scleroderma, Evans syndrome, autoimmune lymphoproliferative syndrome (ALPS), 22q11.2 deletion syndrome
    • Tumors: ovarian, carcinomas, thymomas, dermoid cysts
    • Following hematopoietic stem cell transplant due to alloimmunity and immunosuppression or after solid organ transplants where there is ABO incompatibility between donor and recipient

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