Clinical Information

The cold agglutinin titer test is to be used as a tool in the evaluation of suspected cold agglutinin disease (CAD). CAD is a rare autoimmune hemolytic anemia (AIHA) mediated by cold agglutinins, without any obvious underlying disease. Cold agglutinin syndrome (CAS) is a more rare, secondary cold agglutinin-mediated hemolytic anemia seen with other specific diseases such as Mycoplasma pneumoniae pneumonia, Epstein-Barr virus infection, or aggressive lymphoma. In CAD and CAS, cold agglutinins attach to the patient's erythrocytes causing a variety of symptoms. Symptoms may include chronic anemia due to premature removal of the sensitized erythrocytes from circulation by hemolysis, to acrocyanosis of the extremities (ears, fingers, or toes) due to local blood stasis in the skin capillaries.

Cold agglutinins are defined as autoantibodies that can agglutinate red blood cells at an optimum temperature of 3 - 4°C but can also react at higher temperatures depending on the thermal amplitude. The term “cold agglutinin” arises less from the clinical symptomatology and instead refers to the finding of agglutination without antiglobulin antisera in microtiter wells at 4°C. CAD in 90% of patients is an immunoglobulin M (IgM)–mediated process. Cold agglutinin IgM molecules can be polyclonal or monoclonal, with each associated with a different origin and prognosis. Polyclonal IgM antibodies are typically seen in the post-infectious setting and are self-resolving, although treatment of the underlying infection may hasten resolution. Monoclonal IgM is associated with a long-term disease that often resists treatment and may be associated with an underlying lymphoproliferative disorder.