Blood group antigens are polymorphic residues of protein or carbohydrate on the red cell surface. They can provoke an antibody response in individuals who lack them, and some antibodies can lead to hemolytic transfusion reaction or hemolytic disease of the fetus/newborn (HDFN). Researchers have identified the molecular basis of many red cell blood group antigens, and an actively maintained database currently lists more than 1,600 alleles of 44 genes. A mini-review, published in the March issue of CLN, describes the major applications of the explosion of knowledge in blood group genetics to the practice of blood banking and transfusion medicine.

Blood banks and clinical laboratories routinely type blood donors and patients for ABO and Rh(D), as these are the most critical antigens for safe transfusion, writes Suneeti Sapatnekar, MD, PhD, a transfusion medicine staff physician at Cleveland Clinic in Cleveland, Ohio. Laboratories generally do not type for minor antigens—of the Rh, Kell, Duffy, Kidd, and MNS systems—but they do screen plasma for antibodies against these antigens (antibody screen). If a patient’s antibody screen is negative, units for red blood cell (RBC) transfusion must be ABO- and Rh(D)-compatible. If an antibody to a clinically significant minor antigen is present, units must additionally lack the corresponding antigen.

The red cell phenotype is the complement of antigens on the red cell surface. In transfusion practice, this term refers to the status of clinically significant antigens other than ABO and Rh(D), typically some or all of the following minor antigens: C/c and E/e (Rh system); K/k (Kell system); Fya/Fyb (Duffy system); Jka/ Jkb (Kidd system); and M/N and S/s (MNS system). Red cell phenotype testing of blood donors and donor RBC units is used to identify antigen-negative units for transfusion, usually for patients with red cell antibodies, but sometimes for transfusion-dependent patients without antibodies, to prevent alloimmunization. Phenotype testing is performed by serological typing with specific antisera using direct or indirect (antihuman globulin phase) hemagglutination.

Serological typing methods are simple, but they require reliable typing for antisera, and typing for multiple antigens is labor-intensive. However, standard serological typing cannot be used if the patient was transfused recently, because donor red blood cells can persist in the circulation for up to 3 months after transfusion. Also, standard serological typing cannot be used for many antigens if the patient has a positive direct antiglobulin test (DAT), as only antigens detectable by direct agglutination can be typed. Specialized serological methods can overcome these limitations but are not always successful.

The expression of many clinically significant antigens is determined by single nucleotide polymorphisms (SNPs). Detecting these SNPs can predict the red cell phenotype and is an alternative to serological typing. Multiple SNPs can be included in a single assay, allowing efficient screening for multiple antigens. For this reason, molecular typing is eminently suitable for the mass screening of blood donors and is expected to greatly expand the pool of blood donors (and donor RBC units) who are negative for multiple antigens or negative for a high-prevalence antigen. Molecular typing also provides the means to identify antigen-negative donors when typing antisera are not available.

Pick up the March issue of CLN to learn more about molecular typing.