Clinlab Navigator

Cold Agglutinin Titer

Cold agglutinins are nonspecific IgM antibodies which agglutinate red blood cells at cold temperatures between 0 and 30oC. They usually bind to polysaccharides on the RBC surface. Cold agglutinins can cause acrocyanosis and hemolytic anemia.

Hemolysis is mediated by complement fixation on RBC membranes and phagocytosis. Most cases have extravascular hemolysis, but 15 to 20% of cases have intravascular hemolysis. The latter cases exhibit increased lactate dehydrogenase, decreased haptoglobin and hemoglobinuria. Patients have a positive direct antiglobulin test with anti-C3 due to the fixation of complement by IgM antibody.

The titer of cold agglutinins is the highest dilution of plasma that agglutinates RBCs. Cold agglutinins are present in 95% of healthy patients at titers of 16 or less. Titers less than 32 are considered negative. Titers above 512 are usually clinically relevant, but the best prediction of the biological activity of cold autoantibodies is thermal amplitude, which is the highest temperature at which antibodies agglutinate RBCs. Harmless cold autoantibodies react with RBCs up to a temperature of 10 to 15 degrees C in vitro, while antibodies with potentially harmful effects react in vitro at 30 degrees C or higher.

Cold agglutinins are associated with many infectious diseases including Mycoplasma pneumonia, infectious mononucleosis, legionella, citrobacter, influenza and varicella. Antibodies often appear one to two weeks after infection. Cold agglutinins may also be present in patients with lymphoproliferative disorders. If no underlying condition is detected, a patient may have primary cold agglutinin syndrome.

In the past, cold agglutinin titers were often used as a surrogate test for Mycoplasma pneumonia, since mycoplasma infections are often associated with elevated anti-I titers.   More specific mycoplasma IgG and IgM immunoassays are preferred to diagnose Mycoplasma pneumonia.

Specimen requirement is one 10 mL SST tube of blood. The tube should be immediately placed in a 37 C water bath and allowed to clot. After 10 minutes, the tube can be centrifuged and the serum transported to the laboratory at ambient temperature. If a water bath is not available, the tube should be transported at ambient temperature without centrifugation.

AddThis Social Bookmark Button