Molecular typing for Blood

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. Researchers have identified the molecular basis of many red cell blood group antigens, and an actively maintained database currently lists over 1,600 alleles of 44 genes. This mini-review describes the major applications of the explosion of knowledge in blood group genetics to the practice of blood banking and transfusion medicine.

  • Fetal typing:Typing of fetuses, usually for D, but also K, C, c or E, of alloimmunised women, to assess whether the fetus is at risk of haemolytic disease of the fetus and newborn (HDFN). The DNA source is cell-free fetal DNA in the mother’s plasma. In the future this technology may be applied to all D negative pregnant women to determine their requirement for antenatal anti-D prophylaxis.
  • Transfused patientsTyping of multiply transfused patients, where serological testing cannot be used because of the presence of transfused red cells.
  • Immunoglobulin-coated red cells: Typing of red cells giving a positive direct anti-globulin test (DAT), usually in patients with autoimmune hemolytic anemia, to help in the identification of underlying alloantibodies.
  • Determining Rh variantsMolecular methods are used for identifying Rh variants, especially the weak and partial variants of D, to assist in the provision of the most suitable blood for transfusion.
  • Confirmation of D negative: Detection of RHD in an apparently D negative donor could signal very weak D expression, which could immunize a D negative patient.
  • RHD zygosity: Quantitative PCR can reveal whether a D positive person is homozygous or hemizygous for RHD. This cannot be done by serological methods. Testing fathers of fetuses at risk of HDFN provides limited information on the D type of the fetus.
  • Testing when suitable reagents are not available: Molecular methods can replace serological methods when suitable serological reagents are unreliable or not available, e.g. Dombrock typing of donors.
  • Supporting the serological reference laboratoryMolecular methods are valuable for supporting the serological reference laboratory in sorting out difficult problems.

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