Blood classification is foundational in medicine, with the ABO system being the most widely known. The Rh blood group system holds comparable importance in transfusion medicine and obstetrics. The “Rh” is derived from Rhesus monkeys, where this red blood cell protein was first studied. This factor determines if a person’s blood type is labeled positive or negative.
Defining the Rh Factor
The Rh factor is a specific protein, or antigen, found on the surface of red blood cells. Rh status is determined by the presence or absence of the highly immunogenic Rh D antigen. If the D antigen is present, the person is classified as Rh-positive, accounting for approximately 85% of the population. If the D antigen is absent, the person is classified as Rh-negative.
The inheritance follows a dominant genetic pattern. The RHD gene, responsible for the D antigen, is located on chromosome 1. A person only needs to inherit one copy of the Rh-positive allele to express the D antigen. To be Rh-negative, a person must inherit the Rh-negative allele from both parents, lacking a functional RHD gene.
Compatibility in Blood Transfusions
Rh typing is fundamental before any blood transfusion to prevent a severe immune reaction. An Rh-negative person does not naturally possess antibodies against the D antigen. If they receive Rh-positive blood, their immune system identifies the D antigen as foreign, triggering sensitization and the production of anti-D antibodies.
If the Rh-negative individual is exposed to Rh-positive blood a second time, the pre-formed anti-D antibodies rapidly destroy the transfused red blood cells. This acute reaction, known as a hemolytic transfusion reaction, involves hemolysis that can lead to fever, chills, and organ damage. Rh-negative patients must always receive Rh-negative blood products.
The Rh factor influences the universal blood donor concept. Type O-negative blood is the universal donor for red blood cells because it lacks the A, B, and Rh D antigens. This absence allows O-negative blood to be safely administered in emergencies when the recipient’s blood type is unknown.
Rh Incompatibility and Pregnancy
The most clinically significant implication involves an Rh-negative mother carrying an Rh-positive fetus. This occurs when the mother is Rh-negative and the father is Rh-positive. Although maternal and fetal blood supplies usually remain separate, small amounts of fetal red blood cells can enter the maternal circulation, a process called fetomaternal hemorrhage.
Sensitization most commonly occurs during childbirth when the placenta separates, or during invasive procedures like amniocentesis, miscarriage, or ectopic pregnancy. The mother’s immune system recognizes the fetal D antigen and produces anti-D antibodies. Because this response takes time, the first Rh-positive pregnancy is typically unaffected.
Once sensitized, the mother’s immune system retains a memory of the D antigen, and anti-D antibodies persist. In subsequent Rh-positive pregnancies, these maternal antibodies (IgG) cross the placenta and destroy the fetal red blood cells. This causes Hemolytic Disease of the Newborn (HDN), also known as erythroblastosis fetalis.
HDN results in severe hemolytic anemia in the fetus, causing profound jaundice, liver and spleen enlargement, and heart failure. The most severe form is hydrops fetalis. Since the severity of HDN increases with each subsequent Rh-positive pregnancy, routine prenatal care tests all pregnant individuals to determine Rh status and identify those at risk.
Preventing Sensitization: The Role of Rh Immunoglobulin
The severe complications of Rh incompatibility are largely preventable using Rh immunoglobulin (RhIG), often known as RhoGAM. RhIG is an injectable pharmaceutical containing pre-formed anti-D antibodies derived from human plasma. This treatment provides temporary passive immunity to the Rh-negative mother.
When administered, RhIG antibodies circulate in the mother’s bloodstream and immediately bind to any Rh-positive fetal red blood cells. These coated cells are cleared from the mother’s system before her own immune cells can recognize them and mount an active immune response. The injection prevents the mother’s immune system from becoming sensitized to the D antigen.
RhIG is administered prophylactically at key points during pregnancy when fetomaternal hemorrhage is likely. The standard protocol includes a routine injection around the 28th week of gestation. A second dose is given immediately after delivery if the newborn is confirmed Rh-positive. This preventative measure has drastically reduced the incidence of HDN in modern healthcare.