One of the most common causes of acquired hemolytic anemia is immunologic destruction of red blood cells (RBCs) mediated by autoantibodies directed against antigens on the patient's RBCs. The clinical manifestations of this group of diseases, called autoimmune hemolytic anemia (AIHA), depend greatly upon the type of antibody that is produced by the abnormal immune reaction.
This topic will review the mechanisms underlying AIHA due to cold agglutinins. The clinical features and treatment of this disorder and issues related to another form of cold-related hemolysis, paroxysmal cold hemoglobinuria, are discussed separately. (See "Clinical features and treatment of autoimmune hemolytic anemia: Cold agglutinins" and "Paroxysmal cold hemoglobinuria".)
NATURE OF THE AUTOANTIBODIES
In general, antibodies of two major types, each with specific characteristics, are produced in AIHA:
- IgM antibodies that generally react with polysaccharide antigens on the RBC surface only at temperatures below that of the core temperature of the body. They are therefore called "cold agglutinins." Rarely, IgG antibodies have these reaction characteristics, occurring either alone or with IgM antibodies .
- IgG antibodies that generally react with protein antigens on the RBC surface at body temperature. For this reason, they are called "warm agglutinins" even though they seldom directly agglutinate the RBCs. Rarely, IgM antibodies have these reaction characteristics and readily agglutinate red cells. (See "Pathogenesis of autoimmune hemolytic anemia: Warm agglutinins and drugs".)
- Antibodies of the IgA isotype are much less common and often of unknown significance. They can produce AIHA with either of the above reaction characteristics [2-4].
Antibody detection: the direct Coombs' test — The autoimmune hemolytic anemias are usually diagnosed by demonstrating an abnormality in a single clinical laboratory test, the direct antiglobulin test first described by Coombs and therefore sometimes called the direct Coombs' test. In this test, the RBCs of the patient are washed free of adherent proteins and reacted with antiserum or monoclonal antibodies prepared against the various immunoglobulins, particularly IgG and a fragment of the third component of complement, C3d. If either or both of these are present on the red cell surface, agglutination or some other endpoint will be detected (table 1).