Development and validation of a universal blood donor genotyping platform: a multinational prospective study

Abstract

Each year, blood transfusions save millions of lives. However, under current blood-matching practices, sensitization to non–self-antigens is an unavoidable adverse side effect of transfusion. We describe a universal donor typing platform that could be adopted by blood services worldwide to facilitate a universal extended blood-matching policy and reduce sensitization rates. This DNA-based test is capable of simultaneously typing most clinically relevant red blood cell (RBC), human platelet (HPA), and human leukocyte (HLA) antigens. Validation was performed, using samples from 7927 European, 27 South Asian, 21 East Asian, and 9 African blood donors enrolled in 2 national biobanks. We illustrated the usefulness of the platform by analyzing antibody data from patients sensitized with multiple RBC alloantibodies. Genotyping results demonstrated concordance of 99.91%, 99.97%, and 99.03% with RBC, HPA, and HLA clinically validated typing results in 89 371, 3016, and 9289 comparisons, respectively. Genotyping increased the total number of antigen typing results available from 110 980 to >1 200 000. Dense donor typing allowed identification of 2 to 6 times more compatible donors to serve 3146 patients with multiple RBC alloantibodies, providing at least 1 match for 176 individuals for whom previously no blood could be found among the same donors. This genotyping technology is already being used to type thousands of donors taking part in national genotyping studies. Extraction of dense antigen-typing data from these cohorts provides blood supply organizations with the opportunity to implement a policy of genomics-based precision matching of blood.

Familial pseudohyperkalemia induces significantly higher levels of extracellular potassium in early storage of red cell concentrates without affecting other standard measures of quality: A case control and allele frequency study

“…Here, we have demonstrated a large phenotypic effect of a variant present in around 1 in 400 blood donors that may have implications for blood safety. As more widespread genotyping of blood donors becomes common practice by embedding affordable genotyping arrays in the donor testing regiments for extended red cell grouping and HLA typing, 41 it is likely that other genetic variants will be identified that may impact on donated blood and potentially clinical outcome from transfusion.…”

An open‐source python library for detection of known and novel Kell, Duffy and Kidd variants from exome sequencing

“…We propose that blood antigen interpretation is a universal clinical benefit that could increase the cost‐efficiency of genomic sequencing performed in the clinical setting [14]. To this end, important challenges involve design and validation of bioinformatic pipelines tailored to evaluate blood antigen expression and compatibility, and automation suitable for application to a large number of donor and recipient genomes [13,15–21].…”

Transfusion 2024: A 5‐year plan for clinical and laboratory transfusion in England

“…13 The successful implementation of BBT and PBM initiatives 14 to support the safe and appropriate use of blood components has, however, resulted NHSBT is now a member of the Blood Transfusion Genomics Consortium (BGC), an international collaboration of blood services that has developed a new genotyping array that can measure blood group genotypes accurately and cheaply. 26,27 NHSBT has also established the HAEM-MATCH consortium 28 that aims to develop algorithms to optimise the allocation of genotyped blood to patients and to optimise the collection of blood from the donor pool by type. HAEM-MATCH has recently been awarded £1 million by the NIHR to develop artificial intelligence (AI) methods.…”

“…Alloimmunisation occurs in approximately 5% of all transfused patients with much higher rates of around 30% or more in patients NHSBT is now a member of the Blood Transfusion Genomics Consortium (BGC), an international collaboration of blood services that has developed a new genotyping array that can measure blood group genotypes accurately and cheaply. 26,27 NHSBT has also established the HAEM-MATCH consortium, 28…”