Development and validation of a universal blood donor genotyping platform

17 August 2020

Mr Nicholas Gleadall is a PhD Student in Genomics at the University of Cambridge.

Building on decades of genomics and blood group research, our scientists have developed a rapid, high-throughput and comprehensive test for determining all blood groups in donors. This new test provides the opportunity to transform how we characterise donors and improve our ability to provide matched units for the most vulnerable patients.

Each year millions of blood transfusions provide lifesaving support to patients. However, transfusions are not without complications. As current practices only require blood to be ABO and RhD compatible for general purposes, 1 in 30 patients form antibodies against the minor blood group systems that are absent from the recipients own red blood cells. This has long term health consequences for patients, particularly those who receive regular transfusions due to having sickle cell disease. Identifying compatible units for patients with antibodies becomes more complicated as future transfusions must be from donors who are more precisely matched.

To provide these precisely matched blood transfusions, 1 in 6 donors are typed for far more blood group systems than the standard ABO and RhD. Our researchers at the University of Cambridge have developed a simple-to-use DNA test for typing nearly all the clinically relevant red cell blood groups. See Figure 1. This fully-automated test also generates results for the Human Leukocyte Antigen (HLA), and the Human Platelet Antigen (HPA) types. Knowing the HLA and HPA type allows rapid identification of valuable platelet donors.

Figure 1. Outlines the genotyping process, using the new DNA-based test for determining blood groups, HLA and HPA types.

The performance of this new and affordable test for simultaneously determining a person’s blood group systems, HLA and HPA types, has been compared with the many tests currently used by the blood services in England and the Netherlands. Analysis of the results of nearly 8,000 blood donors showed an excellent level of accuracy at 99.9% in 101,676 comparisons. The new test provides a >10-fold increase in the number of antigen types available from typed donors (increasing from 110,980 to over 1.2 million).  Using real-world data from NHS patients we have shown that the increased information on donor blood groups makes it 2.6 times more likely that a compatible donor will be identified.

The next stage in this exciting project is to bring this precision medicine test to the bedside of NHS patients and increase the number of donors tested.  Planned recruitment of donors to the UK 5 Million Early Disease Detection Research Project will lead to a significant increase in the number of donors being typed with this new test.

The work builds upon our support of the NHS Long-term plan which involves targeted investment in transformative innovation, particularly genomics.

If you would like to learn more, you can read the full publication.