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Blood Rev. 2008 Jan;22(1):1-15. Epub 2007 Sep 27.

Cold antibody autoimmune hemolytic anemias.

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  • 1Pathology and Laboratory Medicine, University of California Los Angeles, StemCyte International Cord Blood Center, Arcadia, California, United States.


The cold antibody autoimmune hemolytic anemias (AIHAs) are primarily comprised of cold agglutinin syndrome (CAS) and paroxysmal cold hemoglobinuria (PCH) but, in addition, there are unusual instances in which patients satisfy the serologic criteria of both warm antibody AIHA and CAS ("mixed AIHA"). CAS characteristically occurs in middle-aged or elderly persons, often with signs and symptoms exacerbated by cold. The responsible antibody is of the IgM immunoglobulin class, is maximally reactive in the cold but with reactivity up to at least 30 degrees C. Therapy is often ineffective, but newer agents such as rituximab have been beneficial in some patients. PCH occurs primarily in children, often after an upper respiratory infection. The causative antibody is of the IgG immunoglobulin class and is a biphasic hemolysin that is demonstrated by incubation in the cold followed by incubation at 37 degrees C in the presence of complement. Acute attacks are frequently severe but the illness characteristically resolves spontaneously within a few days to several weeks after onset and rarely recurs. Treatment consists of supportive care, with transfusions frequently being needed.

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