There are 30 or more known antigens on the surface of blood cells. These form the blood groups or blood types. In a transfusion, the blood groups of the recipient and donor must be matched. If improperly matched, the recipient's immune system will produce antibodies causing clotting of the transfused cells, blocking circulation through capillaries and producing serious or even fatal results.

    ABO blood types are determined by a gene, I (for isoagglutinin). There are three alleles, IA, IB and IO. Proteins produced by the A and B alleles are antigenic. Individuals with blood type A have the A antigen on the surface of their red blood cells, and antibodies to type B blood in their plasma. People with blood type B have the B antigen on their blood cells and antibodies against type A in their plasma. Individuals with type AB blood produce have antigens for A and B on their cell surfaces and no antibodies for either blood type A or B in their plasma. Type O individuals have no antigens on their red blood cells but antigens to both A and B are in their plasma.

    People with type AB blood can receive blood of any type. Those with type O blood can donate to anyone. If a transfusion is made between an incompatible donor and recipient, the recipient's blood will undergo a cascade of events. Reaction of antigens on cells and antibodies in plasma will produce clumping that clogs capillaries, other cells burst, releasing hemoglobin that can crystallize in the kidney and lead to kidney failure. The Rh (for the rhesus monkey in which it was discovered) blood group is made up of those Rh positive (Rh+) individuals who can make the Rh antigen and those Rh negative (Rh-) who cannot.

    Hemolytic disease of the newborn (HDN) results from Rh incompatibility between an Rh- mother and Rh+ fetus. Rh+ blood from the fetus enters the mother's system during birth, causing her to produce Rh antibodies. The first child is usually not affected, however subsequent Rh+ fetuses will cause a massive secondary reaction of the maternal immune system. To prevent HDN, Rh- mothers are given an Rh antibody during the first pregnancy with an Rh+ fetus and all subsequent Rh+ fetuses.