Cold agglutinin disease is a form of autoimmune hemolytic anemia caused by cold-reacting autoantibodies (a type of protein produced by the immune system). Primary cold agglutinin disease is usually associated with monoclonal (produced from a single ancestral cell by repeated cellular replication) cold-reacting autoantibodies. Primary cold agglutinin disease is chronic and occurs after the fifth decade of life, with a peak incidence in the seventh and eighth decades. Secondary cold agglutinin disease is predominantly caused by infection and lymphoproliferative disorders in which lymphocytes (white blood cells) are produced in excessive quantities. It is essential with chronic cold agglutinin disease to keep all body parts warm at all times and avoid cooling of body parts. Appropriate clothing is necessary for cold environments, and avoidance of cold foods and working in cold storage areas is also important.