Chronic Hemolytic Anemia Due to Cold Agglutinins: A 20-Year History of Benign Gammopathy With Response to Chlorambucil

A male, 47, developed chronic hemolytic anemia in association with high titers of cold agglutinins in 1966. His symptoms of the cold agglutinin syndrome began in 1951 with cyanosis of the extremities and face after exposure to cold. In 1956, hemoglobinuria was first noted after chilling. In 1962, the cold agglutinin titer was 1:16,000, and his red cells were coated with complement globulins. In 1966, he developed chronic hemolytic anemia and a macroglobulin M component appeared in the serum protein electrophoresis. The titer of cold agglutinins was 1:64,000. The hemolytic anemia responded to chlorambucil with a decrease in cold agglutinin titer and the level of macroglobulin. Serum complement (C) values returned toward normal. Cessation of chlorambucil was followed by relapse. There was a second response to chlorambucil, but reactivation of the hemolytic anemia occurred following a respiratory infection, despite the reduced titer of cold agglutinin. Chlorambucil was discontinued and has not been administered since. There have been remissions and exacerbations of the hemolytic anemia and a return of the macroglobulin and cold agglutinins toward pretreatment levels. During the past 2 yr there has been spontaneous improvement in his symptoms, and the level of macroglobulin has decreased. Despite the appearance of a monoclonal macroglobulin having kappa light chain and with cold agglutinin activity, there is reason to classify his abnormal immunoglobulin production as benign.