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Sequencing Enables Precise Match for Blood Transfusions

By Labmedica International staff writers
Posted on 30 May 2018
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Image: A blood transfusion bag typed for A Rh negative (Photo courtesy of Sherry Yates Young).
Image: A blood transfusion bag typed for A Rh negative (Photo courtesy of Sherry Yates Young).
There are more than 300 known red blood cell (RBC) antigens and 33 platelet antigens that differ between individuals. Sensitization to antigens is a serious complication that can occur in prenatal medicine and after blood transfusion, particularly for patients who require multiple transfusions.

Although pre-transfusion compatibility testing largely relies on serological methods, reagents are not available for many antigens. Methods based on single-nucleotide polymorphism (SNP) arrays have been used, but typing for ABO and Rhesus, the most important blood groups, cannot be done with SNP typing alone.

Scientists at Brigham and Women's Hospital (Boston, MA, USA) and their colleagues created a database of molecular changes in red blood cell (RBC) and platelet antigens and developed an automated antigen-typing algorithm based on whole-genome sequencing (bloodTyper). This algorithm was iteratively improved to address cis–trans haplotype ambiguities and homologous gene alignments. Whole-genome sequencing data from 110 MedSeq participants (30 × depth) were used to initially validate bloodTyper through comparison with conventional serology and SNP methods for typing of 38 RBC antigens in 12 blood-group systems and 22 human platelet antigens. The bloodTyper was further validated with whole-genome sequencing data from 200 INTERVAL trial participants (15 × depth) with serological comparisons.

The scientists iteratively improved bloodTyper by comparing its typing results with conventional serological and SNP typing in three rounds of testing. The initial whole-genome sequencing typing algorithm was 99.5% concordant across the first 20 MedSeq genomes. Addressing discordances led to development of an improved algorithm that was 99.8% concordant for the remaining 90 MedSeq genomes. Additional modifications led to the final algorithm, which was 99.2% concordant across 200 INTERVAL genomes or 99.9% after adjustment for the lower depth of coverage.

The authors concluded that by enabling more precise antigen-matching of patients with blood donors, antigen typing based on whole-genome sequencing provides a novel approach to improve transfusion outcomes with the potential to transform the practice of transfusion medicine. Connie M. Westhoff, PhD, from the New York Blood Center (New York, NY, USA) and co-first author of the study said, “This approach has the potential to be one of the first routine clinical uses of genomics for medical care for patients needing blood transfusion. It could prevent serious or even fatal complications because once patients are sensitized they have a life-long risk of hemolytic transfusion reactions if blood transfusion is needed in an emergency.” The study was published on May 17, 2018, in the journal The Lancet Haematology.

Related Links:
Brigham and Women's Hospital
New York Blood Center

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