Blood group genotyping

Abstract

Genomics is affecting all areas of medicine. In transfusion medicine, DNA-based genotyping is being used as an alternative to serological antibody-based methods to determine blood groups for matching donor to recipient. Most antigenic polymorphisms are due to single nucleotide polymorphism changes in the respective genes, and DNA arrays that target these changes have been validated by comparison with antibody-based typing. Importantly, the ability to test for antigens for which there are no serologic reagents is a major medical advance to identify antibodies and find compatible donor units, and can be life-saving. This review summarizes the evolving use and applications of genotyping for red cell and platelet blood group antigens affecting several areas of medicine. These include prenatal medicine for evaluating risk of fetal or neonatal disease and candidates for Rh-immune globulin; transplantation for bone marrow donor selection and transfusion support for highly alloimmunized patients and for confirmation of A2 status of kidney donors; hematology for comprehensive typing for patients with anemia requiring chronic transfusion; and oncology for patients receiving monoclonal antibody therapies that interfere with pretransfusion testing. A genomics approach allows, for the first time, the ability to routinely select donor units antigen matched to recipients for more than ABO/RhD to reduce complications. Of relevance, the growth of whole-genome sequencing in chronic disease and for general health will provide patients’ comprehensive extended blood group profile as part of their medical record to be used to inform selection of the optimal transfusion therapy.

Transfusion‐associated adverse events and implementation of blood safety measures ‐ findings from the 2017 National Blood Collection and Utilization Survey

“…Despite the availability of molecular testing that could improve matched component‐recipient compatibility, the uptake of genotyping by both blood collection centers and transfusing facilities remains relatively low. Facilities that performed genotyping did so for only a small percentage of their donors or recipients, which may indicate that testing is performed on a subpopulation of patients, such as those requiring chronic transfusions . As this technology was recently approved by FDA, future surveys will continue to track uptake and barriers to implementation of molecular genotyping in the United States.…”

“…Facilities that performed genotyping did so for only a small percentage of their donors or recipients, which may indicate that testing is performed on a subpopulation of patients, such as those requiring chronic transfusions. 34 As this technology was recently approved by FDA, 19,35 future surveys will continue to track uptake and barriers to implementation of molecular genotyping in the United States.…”

Two case reports involving therapeutic monoclonal anti‐CD47 (Hu5F9‐G4), it's effect on compatibility testing and subsequent selection of components for transfusion

“…These cases highlight the need to complete RBC grouping and extended phenotyping or genotyping prior to the start of treatment. 10 At high titres, following the commencement of Hu5F9-G4 therapy, alloadsorption does not always work and in many places, the availability of reagents or alternative automated platforms remains a barrier to timely resolution. At lower titres, identification of underlying alloantibodies using routine AHG reagents and IAT methodologies may be possible, but this requires extended serological investigation.…”

<p>Potential of next-generation sequencing to match blood group antigens for transfusion</p>

“…Prevention of alloimmunization against antigens other than D is rather limited. [17][18][19] A donor compatible in other antigens is selected only when a patient produces antibodies to a specific antigen. The process of identification of antibody specificity and selection of compatible donor is often complicated and requires multistep laboratory testing by highly qualified staff.…”