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Cold agglutinin disease

Cold agglutinin disease is an acquired autoimmune hemolytic anemia due to an IgM autoantibody usually directed against the I antigen on red blood cells. These IgM autoantibodies characteristically will not react with cells at 37 degrees centigrade but only at lower temperatures.

In the cooler parts of the body (fingers, nose, ears), agglutination of red blood cells by the IgM antibodies will transiently occur. Hemolysis results indirectly from attachment of IgM, which in the cooler parts of the circulation binds and fixes complement. When the red blood cell returns to a cooler temperature, the IgM antibody dissociates, leaving complement on the cell. Lysis, or destruction, of cells rarely occurs. Rather, C3b present on the red cells is recognized by Kupffer cells (which have receptors for C3b).

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Clinical suspicion

Extravascular hemolysis


Extravascular hemolysis, Coomb test is positive for C3.

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