What Are Blood Phenotypes and Why Do They Matter?

Blood phenotypes classify blood based on inherited characteristics found on the surface of red blood cells (RBCs). These characteristics are specific molecules called antigens, which can be proteins, carbohydrates, or glycolipids. The presence or absence of these antigens determines how the immune system recognizes its own blood as “self” and identifies foreign blood as a potential threat. This recognition process governs the safety of medical procedures like blood transfusions and plays a significant role in pregnancy management.

The Primary Classification Systems: ABO and Rh

The two most recognized and clinically significant blood group systems are the ABO and Rh systems, which form the basis of the eight common blood types. The ABO system is defined by the presence or absence of A and B antigens on the red blood cells. The plasma contains corresponding antibodies that attack antigens not present on the person’s own red cells.

For example, Type A blood has A antigens and anti-B antibodies. Type B blood has B antigens and anti-A antibodies, while Type AB has both A and B antigens but no antibodies. Type O blood has neither A nor B antigens, but carries both anti-A and anti-B antibodies.

The Rh system is primarily determined by the presence or absence of the D antigen, often called the Rh factor. If the D antigen is present, the blood type is designated as Rh-positive (+); if absent, the type is Rh-negative (-). Unlike the ABO system, anti-D antibodies are not naturally occurring. They are typically produced only after an Rh-negative person is exposed to Rh-positive blood, such as during a transfusion or pregnancy.

Understanding Compatibility and Transfusion Safety

Matching blood phenotypes is necessary for safe blood transfusions, as incompatible blood can trigger a severe immune reaction. This reaction, known as a hemolytic transfusion reaction, occurs when the recipient’s antibodies bind to the donor’s foreign antigens. This causes the donor red blood cells to clump together (agglutination) and rapidly burst (hemolysis). This destruction can lead to serious complications like shock, kidney failure, and death.

Compatibility rules stem directly from the antigen-antibody relationship. Type O- blood is the “universal donor” because its cells lack A, B, and D antigens, so they will not be attacked by antibodies in any recipient’s plasma. Conversely, an individual with AB+ blood is the “universal recipient.” Their red blood cells possess all three major antigens (A, B, and D), and their plasma contains none of the corresponding antibodies.

The Rh factor presents a specific risk in pregnancy, known as Rh incompatibility or hemolytic disease of the newborn. This occurs when an Rh-negative mother carries an Rh-positive fetus. The mother’s immune system is typically sensitized during delivery by the baby’s Rh-positive red blood cells. The mother’s body then produces anti-D antibodies, which can cross the placenta in subsequent pregnancies and attack the red blood cells of a future Rh-positive fetus. This can cause severe anemia and jaundice in the baby. Fortunately, this condition is largely preventable with the administration of Rh immune globulin, such as RhoGAM, given to Rh-negative mothers around 28 weeks of gestation and after delivery if the baby is Rh-positive.

The Genetics of Blood Type Inheritance

Blood phenotypes are hereditary traits, governed by genes passed down from both parents. The ABO blood group is controlled by a single gene on chromosome 9, which has three main alleles: A, B, and O. The A and B alleles are codominant, meaning that if both are inherited (genotype AB), both A and B antigens are expressed.

The O allele is recessive, expressed as Type O blood (phenotype) only if an individual inherits two O alleles (genotype OO). A genotype of AA or AO expresses the Type A phenotype, while BB or BO results in the Type B phenotype. Understanding the difference between the genetic makeup (genotype) and the expressed characteristic (phenotype) aids in predicting the blood types of offspring.

Rh factor inheritance follows a dominant-recessive pattern. The presence of the Rh factor (Rh-positive) is a dominant trait, meaning a person is Rh-positive if they inherit at least one Rh-positive allele. Conversely, a person is Rh-negative only if they inherit two Rh-negative alleles, one from each parent. The combination of the ABO and Rh systems results in the eight common blood types, such as A+ or O-.

Beyond ABO and Rh: Minor Blood Group Systems

While ABO and Rh are the most common, the International Society of Blood Transfusion (ISBT) recognizes dozens of other blood group systems, sometimes called minor systems. These systems include the Kell, Duffy, Kidd, and MNS groups, each defined by their own set of antigens. Although less likely to provoke an immune response than ABO antigens, these minor groups are still clinically significant.

These minor antigens are important for patients who require repeated blood transfusions, such as those with chronic illnesses like sickle cell disease. Repeated exposure to foreign red blood cells can cause the patient’s immune system to develop antibodies against these minor antigens, a process called alloimmunization. If subsequent transfusions are not matched, the patient can experience delayed hemolytic transfusion reactions. Identifying these specific antibodies and matching for the corresponding minor phenotypes is necessary to provide safe, compatible blood.