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In Cold Antibody Autoimmune Hemolytic Anemia (AIHA), the anti-ABO antibodies typically react at temperatures well below normal, specifically in the cooler range of the body, often between 0-10 degrees Celsius. This characteristic is a key feature of cold agglutinin disease, where the antibodies are IgM type. These antibodies become activated and agglutinate red blood cells at lower temperatures, such as when blood circulates in peripheral areas of the body, like the extremities, that may be cooler.

The reaction at these lower temperatures can lead to hemolytic anemia when the antibodies bind to the red blood cells, causing their destruction. This is contrasted with other types of hemolytic anemias, where the antibodies react at normal or elevated body temperatures. Understanding this distinction is crucial for recognizing the clinical manifestations and laboratory findings associated with Cold AIHA.