The classification of blood into A, B, AB, and O types is based on specific proteins, known as antigens, present on the surface of red blood cells. However, this is only part of the full blood typing picture. The designation of a blood type as “positive” or “negative” refers to a separate, but equally important, characteristic called the Rhesus (Rh) factor. This factor determines a patient’s compatibility for transfusions and introduces specific medical considerations, particularly in obstetrics.
Defining the Rh Factor
The Rh factor is a collection of antigens, with the most significant being the RhD protein, often simply called the D antigen. This D antigen is a large, highly immunogenic protein embedded in the red blood cell membrane. A person is classified as Rh positive if their red blood cells carry the D antigen, which accounts for the vast majority of the global population. Conversely, an individual is Rh negative if their red blood cells completely lack the D antigen. If an Rh-negative person is exposed to Rh-positive blood, their immune system recognizes the D antigen as a foreign invader, leading to the creation of anti-D antibodies. These antibodies can cause a severe immune reaction upon subsequent exposure.
Universal Donor Status and Transfusions
The Rh status is fundamental in transfusion medicine due to the potent immune response the D antigen can provoke. Patients with Rh-positive blood can generally receive either Rh-positive or Rh-negative blood. For Rh-negative individuals, the transfusion protocol is much stricter; they must receive only Rh-negative blood. A transfusion of Rh-positive blood to an Rh-negative patient sensitizes their immune system, leading to the creation of anti-D antibodies. Subsequent exposure to Rh-positive blood would cause a life-threatening hemolytic transfusion reaction, destroying the transfused red blood cells.
This principle makes O-negative blood uniquely valuable as the “universal donor.” Type O blood already lacks the A and B antigens that trigger reactions in the ABO system. Combining the O status with the Rh-negative status means O-negative blood lacks the A, B, and D antigens, making it compatible with all eight major blood types in an emergency setting. Because O-negative blood can be given when a patient’s blood type is unknown, it is constantly in high demand in hospitals and emergency services.
Rh Incompatibility in Pregnancy
The most significant medical implication of Rh-negative blood involves pregnancy when the mother is Rh negative and the fetus is Rh positive. This Rh incompatibility poses a serious threat to the baby, particularly in subsequent pregnancies. During delivery, or sometimes earlier, a small amount of the baby’s Rh-positive red blood cells may cross the placenta and enter the mother’s bloodstream.
The mother’s immune system recognizes the fetal D antigen as foreign and begins to produce anti-D antibodies, a process called sensitization. While sensitization usually occurs too late in the first pregnancy to affect that baby, the antibodies remain in the mother’s system. In a later pregnancy with another Rh-positive fetus, these maternal anti-D antibodies can cross the placenta. Once in the fetal circulation, the antibodies rapidly attack and destroy the baby’s red blood cells, leading to Hemolytic Disease of the Fetus and Newborn (HDFN). HDFN can cause jaundice, liver and heart failure, and in severe cases, death of the fetus or newborn.
Rh incompatibility is largely preventable through the use of an injection called RhoGAM, or Rh immune globulin. RhoGAM is a purified solution of anti-D antibodies given to the Rh-negative mother, typically around the 28th week of pregnancy and again shortly after delivery of an Rh-positive baby. The injected antibodies bind to any fetal Rh-positive red blood cells that entered the mother’s circulation. By coating these cells, RhoGAM prevents the mother from mounting her own long-lasting antibody response. This prophylactic treatment has reduced the risk of Rh sensitization from approximately 15% to less than 1%.
Prevalence and Inheritance
The trait for Rh-negative blood is significantly less common than Rh-positive blood across the world. Globally, only about 6% of the population is Rh negative, while approximately 94% are Rh positive. In the United States, this number is slightly higher, with around 15% of the population being Rh negative. The highest concentrations of Rh-negative blood types are found in populations of European descent, where prevalence can reach 15% to 20%.
The inheritance of the Rh factor follows standard genetic rules, with the Rh-positive trait being dominant over the Rh-negative trait. A person must inherit the gene for the Rh-negative trait from both parents to be Rh negative. If a person inherits even one copy of the Rh-positive gene, they will be Rh positive. Because the negative trait is recessive, it can remain “hidden” across generations until two carriers have a child.