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Cold Hemagglutinin Disease (CHD)

Cold hemagglutinin disease (CHD) or cold agglutinin syndrome (CAS) represents about 18% of autoimmune hemolytic anemia cases. A cold autoantibody that reacts between 4°C and 30°C can cause a moderate, chronic anemia. The antibody involved is usually IgM, which activates complement. Antibody specificity is usually anti-I.
CHD is predominantly in individuals over 50 years of age. Symptoms generally occur in the winter months and include acrocyanosis of the hands, feet, ears and nose and numbness in the extremities. Cold weather activates the cold autoantibody. It agglutinates red cells in the capillaries of the extremities and fixes complement, causing hemolysis. Patients may exhibit hemoglobinuria, weakness, pallor, and weight loss. Patients may also exhibit jaundice and Raynauds disease. Most patients with CHD live more comfortably in warmer climates.
Laboratory findings include a positive direct antiglobulin test (DAT) with complement only and reticulocytosis. The peripheral smear may demonstrate agglutinated red blood cells (RBCs), as indicated by the arrows in the upper image on the right, and/or polychromatophilic RBCs, as indicated by the arrows in the lower image on the right. Agglutination of red cells may cause difficulties when testing a CBC.
Most patients with CHD do not require transfusion, but when they do, challenges present during pretransfusion testing, including ABO discrepancies or masking of alloantibodies.
CHD can also occur secondary to infection, including Mycoplasma pneumoniae infection, where the cold autoantibody is anti-I and infectious mononucleosis, where the cold autoantibody in most cases is anti-i . Usually the hemolytic episode is resolved when the infection subsides.