Blood groups are fundamental classifications of human blood, allowing for safe medical procedures. The Rh factor is one of the most significant blood group systems, second only to the ABO system. Understanding this factor is crucial because its presence or absence determines blood compatibility, particularly during transfusions and pregnancy. Identifying this system dramatically reduced fatalities and solved a major medical mystery in obstetrics.
The Known Landscape of Blood Before Rh
Before the Rh factor was known, blood compatibility centered on the ABO system, identified by Karl Landsteiner in 1900 and 1901. Landsteiner discovered that mixing blood sometimes caused red blood cells to clump together, a process called agglutination. This reaction led to the classification of blood into A, B, and O groups, explaining many severe reactions seen in early transfusions.
The application of ABO typing in 1907 made blood transfusion a viable medical treatment. However, unexplained transfusion failures and immune reactions continued to occur, suggesting an unknown factor was involved. A particular concern was erythroblastosis fetalis, a severe condition in newborns whose cause was unknown. These persistent problems indicated that the ABO system alone did not account for all aspects of blood compatibility.
Pinpointing the Rh Factor Discovery
The answer to unexplained blood reactions arrived in the late 1930s through the collaborative work of Karl Landsteiner and Alexander S. Wiener. Initial findings occurred in 1937, with the definitive publication confirming its significance in 1940. The discovery involved injecting rabbits and guinea pigs with Rhesus monkey red blood cells, causing the animals to produce an antibody.
Researchers found this antibody also reacted with the red blood cells of a large percentage of humans. This unidentified antigen was named the “Rh factor” or Rhesus factor, after the monkeys used in the experiment. The presence of this factor in human blood provided a biological explanation for hemolytic reactions that occurred even when ABO types were matched.
Understanding the Rh System
The Rh factor is a protein located on the surface of red blood cells, and its presence or absence determines a person’s Rh status. If an individual has this protein, specifically the D antigen, they are considered Rh-positive. Conversely, a person who lacks the D antigen is classified as Rh-negative.
Unlike the ABO system, anti-Rh antibodies are not naturally present in an Rh-negative person’s blood unless they have been “sensitized.” Sensitization occurs when an Rh-negative individual is exposed to Rh-positive blood, such as during a transfusion or pregnancy. This exposure triggers the immune system to produce antibodies against the foreign D antigen, which can cause severe reactions upon subsequent exposure.
Medical Revolution Following the Discovery
The identification of the Rh factor immediately impacted transfusion medicine and maternal-fetal health. For transfusions, Rh compatibility testing became mandatory alongside ABO typing. This new testing drastically reduced severe hemolytic transfusion reactions, making the procedure safer for patients. The RhD antigen is highly immunogenic, emphasizing the necessity of this compatibility check.
The discovery also solved the mystery of hemolytic disease of the newborn (HDN). HDN occurs when an Rh-negative mother’s immune system attacks the red blood cells of her Rh-positive fetus. Sensitization happens during a first pregnancy, allowing antibodies to cross the placenta and attack the baby’s blood in subsequent pregnancies. The development of preventative treatments, particularly Rh immune globulin (RhoGAM), has virtually eliminated HDN as a major cause of fetal and infant death. RhoGAM is administered to Rh-negative mothers during and after pregnancy to prevent the immune system from becoming sensitized, protecting future Rh-positive fetuses.