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Automated genotyped matching of platelets to prevent alloimmunisation

1University of Cambridge, NHS Blood and Transplant, Blood transfusion Genomics Consortium, Cambridge, England, United Kingdom, 2Barts Health NHS Trust, Royal London Hospital, London, England, United Kingdom, 3Royal London Hospital Haemophilia Centre, Royal London Hospital, Barts Health NHS Trust, London, England, United Kingdom, 4Department of Haematology, Barts Health NHS Trust, London, United Kingdom, London, England, United Kingdom, 5Haematology Laboratory, Royal London Hospital, Barts Health NHS Trust, London, England, United Kingdom, 6Department of Haematology, Barts Health NHS Trust, London, United Kingdom and NHS Blood and Transplant, United Kingdom, London, England, United Kingdom, 7Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK., Cambridge, England, United Kingdom, 8Oxford University Hospitals/NHS Blood and Transplant, Oxford, England, United Kingdom, 9Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, UK., Cambridge, England, United Kingdom, 10Department of Haematology, University of Cambridge and NHS Blood and Transplant, NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, CB2 0PT, UK. Department of Haematology, University College London Hospitals, London, NW1 2BU, UK, Cambridge, England, United Kingdom, 11MRC Biostatistics Unit, Cambridge Institute of Public Health, University of Cambridge, Cambridge, UK, Cambridge, England, United Kingdom, 12Barts Health NHS Trust, London, England, United Kingdom

Abstract Number: PB0151

Meeting: ISTH 2022 Congress

Theme: Diagnostics and OMICs » Blood Components and Management

Background: Immunisation against HLA antigens results in adverse healthcare outcomes and significantly increased costs for inherited platelet disorder (IPD) and haemato-oncology patients requiring platelet transfusions. In a single tertiary London centre two of 17 patients with Glanzmann Thrombasthenia or Bernard Soulier Syndrome are refractory to random platelets because of HLA-antibodies. Sourcing HLA-matched platelets for these patients is not possible and costly treatments with activated recombinant-Factor VII are required. These immunisations are avoidable with a sufficiently HLA-typed donor pool.

Aims: To apply population-scale genotyping for provision of HLA-matched platelets.

Methods: The Blood transfusion Genomics Consortium (BGC) has developed an affordable genotyping array capable of typing all red cell, platelet (HPA) and HLA antigens at two-field resolution. Validation has been performed using DNA samples from 14,000 donors from 7 BGC-participating blood services. HPA and HLA types were inferred from the data using the bloodTyper and HLA:IMPUTE02 algorithms.

Results: Genotyping demonstrated concordance of 99.03% at two-field resolution with clinically validated HLA typing results (Fig.1). Using the dense genotyping data for the donors in this study, we were able to identify 8 and 114 exact HLA matched donors for the two IPD patients with HLA-antibodies, where through standard care none could be identified due to a lack of HLA-typing data.

Conclusion(s): We present an affordable array-based genotyping platform which has immediate value in increasing the availability and match quality of HLA-matched platelet concentrates for IPD and Haemato-Oncology patients. Currently, regulatory approval is sought and the technology has been introduced in several national blood services. In the near future full HLA and HPA antigen types will become available for millions of donors worldwide, providing the opportunity to implement a policy of genomics-based precision platelet matching.

Figure 1

Figure 1 – Concordance between clinical and array inferred HLA antigen typing results. Concordance per antigen is shown as a percentage of the total number of comparisons -given at the top of each bar- with concordant and discordant results in green and red, respectively. The concordance was assessed at group, string and allele match levels.

To cite this abstract in AMA style:

Gleadall N, Fenton R, Hart D, Winter P, Lee K, Booth C, Walker L, Stanworth S, Genomics Consortium B, Ouwehand W, Astle W, Sivapalaratnam S. Automated genotyped matching of platelets to prevent alloimmunisation [abstract]. https://abstracts.isth.org/abstract/automated-genotyped-matching-of-platelets-to-prevent-alloimmunisation/. Accessed October 1, 2023.

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