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Secondary cold agglutinin syndrome occurs when autoantibodies bind to red blood cells, rendering them subject to attack by the complement system. [17] It is a result of an underlying condition potentially associated with either monoclonal cold-reacting autoantibodies or polyclonal cold-reacting autoantibodies [16] predominantly caused by infection or lymphoproliferative disorders. [16]
People with cold agglutinin disease produce antibodies against their own red blood cells that cause them to spontaneously agglutinate at room temperature, leading to false positive reactions in forward grouping. Cold agglutinins can usually be deactivated by warming the sample to 37 °C (99 °F) and washing the red blood cells with saline.
Testing with polyspecific and IgG-specific antiglobulin agents is usually negative, and that with C3-specific agent may be positive. On excluding warm autoimmune hemolytic anemia (WAIHA), the cold agglutinin titer should be examined for cold agglutinin disease (CAD). The diagnosis of PCH is suspected when both WAIHA and CAD are excluded.
Cold agglutinins, or cold autoantibodies, occur naturally in nearly all individuals. These natural cold autoantibodies occur at low titers, less than 1:64 measured at 4 °C, and have no activity at higher temperatures. Pathologic cold agglutinins occur at titers over 1:1000 and react at 28-31 °C and sometimes at 37 °C.
Primary cold agglutinin disease is idiopathic, meaning the phenomenons of agglutinations of the red blood cells and hemolysis reaction occurring outside the vessels are absent from any underlying cause. [3] Nevertheless, what is known is, those with idiopathic cold agglutinin disease are susceptible to having or developing mild clonal bone ...
Red cell agglutination in a patient with cold agglutinin disease. In hematology, red cell agglutination or autoagglutination is a phenomenon in which red blood cells clump together, forming aggregates. It is caused by the surface of the red cells being coated with antibodies.
In cold agglutinin disease, the monospecific DAT is by definition positive for the complement molecule C3d but IgM may be negative as the molecule may detach at the time of testing. [4] The diagnosis of cold agglutinin disease is confirmed with an elevated cold agglutinin titer. [4]
About half of the cases are of unknown cause, with the other half attributable to a predisposing condition or medications being taken. Contrary to cold autoimmune hemolytic anemia (e.g., cold agglutinin disease and paroxysmal cold hemoglobinuria) which happens in cold temperature (28–31 °C), WAIHA happens at body temperature. [citation needed]
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