Chronic Hemolytic Anemia Due to Cold

A male, 47, developed chronic hemolytic anemia in association with hi9h titers of cold agglutinins in 1 966. His symptpm of the cold agglutinin syndrome began in 1 951 with cyanosis of the extremities nd face after exposure to cold. In 1 956, hemoglobinuna was first noted after chilling. In 1 962, the cold agglutinin titer was 1 : 1 6,000, and his red cells were coated with complement globulins. In I 966, h#{216} developed chronic hemolytic anemie 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 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. C HRONIC HEMOLYTIC ANEMIA with acrocyanosis due to cold agglutinins is a manifestation of macroglobulinemia in which a relatively small increase in the abnormal protein can produce intravascular red cell agglutination leading to stasis and cyanosis in the skin and mucous membranes. Hemoglobinuria from acute red cell destruction may follow episodes of chilling although this is not a uniform occurrence. Finally, some patients develop a chronic hemolytic anemia that persists despite maintenance of a warm environment. In this report, studies of a middle-aged male with a 20-yr history of symptoms of the cold agglutinin syndrome are presented. The slow progression of his disorder can be attributed to both a gradual increase in cold agglutinin titer and its thermal amplitude. Recent studies of the interaction of cold agglutinins and complement permit some tentative explanations of the course of his hemolytic disease, though obscurities of the mechanism remain.’ Response