Abstract
AbstractEach 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.
Highlights
The European Blood Alliance collects 31 million units of blood each year to provide life-saving support to an estimated 15 million individuals with a wide range of medical conditions.[1]
Sensitization to non–self red blood cells (RBCs) antigens remains an unavoidable consequence of this matching strategy.[2,3,4]
An estimated 3% (0.5 million) of patients become sensitized to RBC antigens after a single transfusion episode, with 60% of patients who receive regular transfusions becoming immunized.[5,6,7,8,9,10]
Summary
The European Blood Alliance collects 31 million units of blood each year to provide life-saving support to an estimated 15 million individuals with a wide range of medical conditions.[1]. An estimated 3% (0.5 million) of patients become sensitized to RBC antigens after a single transfusion episode, with 60% of patients who receive regular transfusions becoming immunized.[5,6,7,8,9,10] Sensitization confers a lifetime risk of HTRs, which from 2013 through 2017 were responsible for 17% (32 of 185) and 6% (7 of 110) of transfusion-related deaths reported to the US Food and Drug Administration and Serious Hazards of Transfusion UK, respectively.[11,12] Sensitization can render transfusion-dependent patients nontransfusable and cause hemolytic disease in pregnancy, which is potentially life threatening to the fetus Notwithstanding these serious side effects, the introduction of a more precise matching policy is resisted because of perceived logistical challenges and donor typing costs.[13]
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