Determining a person’s blood type requires classification by the Rhesus (Rh) factor, in addition to the ABO system. The Rh factor refers to the presence or absence of a specific protein, the D antigen, on the surface of red blood cells. A person is considered Rh-negative if this protein is absent. While this status does not affect overall health, it carries significant implications in two medical scenarios: blood transfusions and pregnancy. The risks associated with being Rh-negative center on preventing an immune response that targets the D antigen as a foreign invader.
What Defines Rh Negative Blood
The Rh factor involves over 50 different surface proteins, but “Rh-negative” primarily refers to the absence of the D antigen. This D antigen is highly immunogenic, meaning it is likely to trigger an immune reaction if introduced into a person who lacks it. The presence or absence of this antigen is determined by the inheritance of the RHD gene.
A person is Rh-positive if they inherit at least one copy of the functional RHD gene. Rh-negative individuals inherit two non-functional copies, resulting in the lack of the D antigen protein. Globally, the Rh-negative blood type is statistically less common, found in approximately six percent of the population, though prevalence is higher among people of European descent.
Importance in Blood Transfusions
The immune system of an Rh-negative person does not naturally produce anti-D antibodies. These antibodies are only produced after an initial exposure to Rh-positive blood, a process called sensitization. Once sensitized, the immune system will rapidly react against any subsequent Rh-positive blood, causing severe incompatibility.
If an Rh-negative patient receives Rh-positive blood, the anti-D antibodies trigger a hemolytic transfusion reaction. The recipient’s immune system attacks and destroys the transfused red blood cells (hemolysis). This rapid destruction can lead to serious complications including fever, shock, kidney failure, and death. For this reason, Rh-negative patients must always receive Rh-negative blood products.
Understanding Rh Incompatibility in Pregnancy
The primary risk associated with being Rh-negative is related to pregnancy when the mother is Rh-negative and the fetus is Rh-positive (Rh incompatibility). This occurs when the father is Rh-positive and the fetus inherits the dominant Rh-positive trait. Sensitization, where the mother’s immune system views the fetal red blood cells as foreign, typically does not happen during the first pregnancy.
Sensitization usually occurs when fetal blood crosses the placenta into the mother’s circulation, most commonly during delivery. Events such as miscarriage, ectopic pregnancy, or trauma can also cause this mixing of blood, known as fetomaternal hemorrhage. The mother’s body begins to produce anti-D antibodies, which are typically Immunoglobulin G (IgG) and can cross the placenta.
Once the mother is sensitized, the risk applies to all subsequent Rh-positive pregnancies. The maternal anti-D antibodies cross the placenta and destroy the fetal red blood cells. This results in Hemolytic Disease of the Fetus and Newborn (HDFN), which can cause the fetus to develop severe anemia and an increase in bilirubin levels. Untreated, HDFN can lead to heart failure, neurological damage (kernicterus), or fetal death.
Preventing Sensitization and Managing Rh Status
Modern medical management has made Rh incompatibility a largely preventable condition. Management involves screening all pregnant individuals to determine their Rh status and conducting an antibody screen, often called an indirect Coombs test, to check for pre-existing anti-D antibodies. If the mother is Rh-negative and has not been sensitized, prophylactic treatment is used to prevent the immune response.
The intervention involves administering an injection of Rh immune globulin, commonly known as RhoGAM. This medication is a preparation of anti-D antibodies derived from donor plasma. When injected into the Rh-negative mother, these exogenous antibodies circulate and destroy any fetal Rh-positive red blood cells that may have entered the maternal bloodstream. This prevents the mother’s immune system from mounting a lasting immune response.
RhoGAM is typically administered prophylactically around the 28th week of gestation for all Rh-negative mothers, especially if the fetal Rh status is unknown. A second dose is administered within 72 hours following the delivery of an Rh-positive baby. The medication is also given following any event that could cause fetomaternal hemorrhage, such as amniocentesis, chorionic villus sampling, or a threatened miscarriage. This proactive strategy has drastically reduced the incidence of HDFN, protecting subsequent pregnancies from the damaging effects of Rh incompatibility.