Hemolytic Anemia

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Autoimmune Hemolytic Anemia

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• Cold Agglutinin Disease

  • autoimmune disease, usually IgM directed against red blood cells

  • antibodies only bind RBCs at low body temperatures, typically 28-31 °C.

  • primary (arising spontaneously)

    • lymphoproliferative disease (lymphoma, chronic lymphoid leukemia, infection, Waldenström's macroglobulinemia 

  • secondary (a result of another pathology)

    • Mycoplasma pneumonia, mononucleosis, and HIV

  • Treatment

    • Avoid cold weather.

    • Treat the underlying lymphoma.

    • No cold drinks; all drinks should be at normal temperature.

    • Requires Heater to maintain temperature in cold places.

    • Treatment with rituximab has been described

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All individuals have circulating antibodies directed against red blood cells, but their concentrations are often too low to trigger disease (titers under 64 at 4 °C). In individuals with cold agglutinin disease, these antibodies are in much higher concentrations (titers over 1000 at 4 °C). Binding of antibodies to red blood cells activates the classical pathway of the complement system. If the complement response is sufficient, red blood cells are damaged by the membrane attack complex (MAC). If the complement response is insufficient to form membrane attack complexes, then extravascular lysis will be favored over intravascular red blood cell lysis. In lieu of the membrane attack complex, complement proteins (particularly C3b and C4b) are deposited on red blood cells. This opsonization enhances the clearance of red blood cell by phagocytes in the liver, spleen, and lungs, a process termed extravascular hemolysis.

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