in the sera of healthy subjects as well as in patients with AIHA of the cold reactive types. CA bind to erythrocyte surface antigens at a temperature optimum of 0–4 °C. In contrast to polyclonal CA in healthy individuals, monoclonal CA often have a high-thermal amplitude, which contributes to their pathogenicity at temperatures approaching 37 °C. Binding of CA causes agglutination of erythrocytes and the antigen–antibody complex induces complement (C) activation and hemolysis. Essential clinical manifestations of primary CAD are hemolytic anemia and cold-induced circulatory symptoms. Exact estimates of the severity of anemia and the frequency of cold-induced symptoms, however, have not been provided until recent years. See also Cold shock response Donath–Landsteiner hemolytic anemia List of hematologic conditions Paroxysmal cold hemoglobinuria Warm antibody autoimmune hemolytic anemia References External links Autoimmune diseases Acquired hemolytic anemia Cold autoimmune hemolytic anemia