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Antigens systems important in transfusion medicine comprise red blood cell (RBC), platelet, neutrophil, and the widely distributed human leukocytes (HLA) antigens.

The study of RBC antigens and antibodies forms the foundation of transfusion medicine. Serologic studies initially characterized these antigens, but now the molecular composition and structure of many are known. Antigens, either carbohydrate or protein, are assigned to a blood group system based on the structure and similarity of the determinant epitopes. Other cellular blood elements such as platelets and plasma proteins are also antigenic and can result in alloimmunization, the production of antibodies directed against antigenic determinants of another individual. These antibodies, called alloantibodies, can comprise anti-RBC Abs, anti-human platelet antigens (HPA) Abs, as well as anti-human leukocytes antigens (HLA) Ab.

Antibodies directed against RBC antigens may result from “natural” exposure, particularly to carbohydrates that mimic some blood group antigens that are present in the environment, particularly saprophyte bacteria. Those antibodies that occur via natural stimuli are usually produced by a T cell–independent response (thus, generating no immune memory) and are mainly IgM isotype. Autoantibodies (antibodies against autologous blood group antigens) arise spontaneously or as the result of infectious sequelae (e.g., from Mycoplasma pneumoniae) and are also often IgM. These antibodies are often clinically insignificant due to their low affinity for antigen at body temperature. However, IgM antibodies can activate the complement cascade and result in hemolysis. Autoantibodies can also arise in an autoimmune setting with most often an IgG isotype. Antibodies that result from allogeneic exposure, such as transfusion or pregnancy, are usually IgG. IgG antibodies commonly bind to antigen at warmer temperatures and may hemolyze RBCs. Unlike IgM antibodies, IgG antibodies can cross the placenta and bind fetal erythrocytes bearing the corresponding antigen, resulting in hemolytic disease of the newborn, or hydrops fetalis. The same holds true for IgG directed against HPA antigens on platelets that can lead to fetal or neonatal immunization and result in intracranial hemorrhage.

Recipient alloimmunization to leukocytes, platelets, and plasma proteins may also result in transfusion complications such as fevers and urticaria as well as platelet transfusion refractoriness, but generally does not cause hemolysis. Such an alloimmunization in the blood donor may also result in a severe lung disorder called transfusion-related acute lung injury (TRALI). Assay for these non-hemolytic alloantibodies is not routinely performed; however, they may be detected using special assays.


The first blood group antigen system, recognized in 1900, was ABO, the most important in transfusion medicine. The major blood groups of this system are A, B, AB, and O. O type RBCs lack A or B antigens. These antigens are carbohydrates attached to a precursor backbone, may be found on the cellular membrane either as glycosphingolipids or glycoproteins, and are secreted into plasma and body fluids as glycoproteins. H substance is the ...

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