Management of cold haemolytic syndrome

Most haemolytic disease is mediated by immunoglobulin G (IgG) antibodies and leads to red blood cell destruction outside of the circulatory system. However, rare syndromes, such as paroxysmal cold haemoglobinuria, show IgG antibodies causing intravascular destruction. Haemolysis may also occur because of immunoglobulin M antibodies. Historically, these antibodies have been termed 'cold agglutinins' because they cause agglutination of red blood cells at 3°C. Cold agglutinin haemolytic anaemia has been associated with a number of autoimmune and lymphoproliferative disorders, and its management differs substantially from warm antibody-mediated haemolytic anaemia. This review of cold haemolytic syndromes describes new therapies and clinical strategies to determine a correct diagnosis.