Another common group of surface antigens that coincides with the ABO blood group is known as the RhD blood group, which received its name based on its initial discovery in the rhesus monkey. The Rh blood group system includes a number of different surface antigens, the most important of which is known as the D antigen or Rhesus (Rh) factor. An individual is considered to be either Rh positive or Rh negative depending on the presence or absence of the D antigen. For instance, the blood type of an individual whose erythrocytes possess the A, B, and D surface antigens is AB positive (AB+). If that individual did not possess the D surface antigen, then they would be considered AB negative (AB-), which incidentally is the least abundant blood type. Around 85% of the world’s population is Rh positive. Thus, for 85% of the population the presence or absence of the Rh factor is irrelevant to transfusions, as they have no anti RhD antibodies. However, it is critical that the other 15% of the population receive only erythrocytes lacking the RhD antigen, as the dangers of agglutination exist with regard to the Rh factor as well.

Rh sensitization, or the production of anti-Rh antibodies in Rh negative individuals, only occurs upon contact with Rh positive erythrocytes. There appears to be no alternative route of exposure such as one found in the ABO blood group system (ie., food and bacteria). Owing to this, it is possible that an Rh-negative individual may show very few negative effects from an initial incompatible Rh-positive transfusion. This is due to the fact that anti-Rh antibodies must build up gradually in the recipient’s blood. However, should this same Rh-negative individual receive a second Rh positive blood transfusion, anti-Rh antibodies will already be present and agglutination and hemolysis will occur swiftly with devastating results.