What Is Cold Agglutinin Disease?

Cold agglutinin disease is a type of autoimmune disease that is characterized by antibodies agglutinating, or sticking to, red blood cells (RBCs). It is a variation of autoimmune hemolytic anemia, in which agglutination leads to the red blood cells dying — an occurrence known as hemolysis. Cold agglutinin disease is set apart from autoimmune hemolytic anemia, however, in that the antibodies only stick to red blood cells at low temperatures, at the approximate range of 39.2 to 98.6°F (4 to 37°C). Thus, such antibodies are referred to as cold agglutinins.

In 1903, Austrian-born Jewish American physician and chemist Karl Landsteiner made the first description of the existence of cold agglutinins. It was in 1957, however, that a trio of medical researchers with the surnames of Dacie, Crookston and Christenson made the first report of cold agglutinin hemolysis, thus marking the first description of cold agglutinin disease. Eventually, the antibody most commonly associated with the medical condition became immunoglobulin (Ig), usually the IgA, IgG or IgM variant.

Two forms of cold agglutinin disease exist: primary disease and secondary disease. The primary type is described as idiopathic and chronic, meaning that its cause is unknown and that it is long lasting. Primary disease occurs from monoclonal antibodies, or antibodies that originate from the same cell. Secondary disease is usually triggered from another condition, usually another autoimmune disease, infection or a tumor. Also, it is typically generated by both monoclonal and polyclonal antibodies, the latter originating from different cells.

Cold agglutinin disease is most common in the elderly, particularly people in their 60s and 80s. The secondary polyclonal form of the disease in particular often affects younger people. In terms of gender, females are more commonly affected than males.

The most common symptom of cold agglutinin disease is anemia, which is the reduction of the number of RBCs or the amount of hemoglobin in the blood. Other common signs include painful and discolored toes and fingers; chronic fatigue; hemoglobinuria, or the release of high concentrations of hemoglobin from urine; and respiratory problems. People with the primary form of cold agglutinin disease might have the symptoms worsen during colder weather due to the low temperatures under which the cold agglutinins work optimally.

The best treatment for cold agglutinin disease is prevention. This means that staying away from cold weather or dressing warmly are the most effective measures people can take. In more extreme cases, however, physicians rely on the monoclonal antibody Rituximab, steroid hormones such as glucocorticoids, and immunosuppressive and immunomodulating drugs. Such treatments are used sparingly though, due to questionable effectiveness or their potentially harmful side effects.