A National Programme of a High Throughput Axiom Array Genotyping Platform for HEA and HLA Testing for All Patients with Sickle Cell, Thalassaemia and Transfusion Dependent Rare Inherited Anaemias in the United Kingdom

In January 2024 the National Health Service (NHS) (NHS England (NHSE) and NHS Blood and Transplant (NHSBT)), launched a programme of typing for 56 Human Erythroid Antigen (HEA) types and Human Leukocyte Antigen (HLA) Class I and II types, at first field resolution by Axiom array genotyping. The test was free at the point of testing, to all patients with sickle cell (SCD), thalassaemia and transfusion dependent rare inherited anaemias in England. This was the clinical deployment of a next version of the Universal Blood Donor Typing array (Gleadall, 2021) developed by the Blood transfusion Genomics Consortium (www.bgc.io) and the first step in the programme for algorithmically driven genomically informed matching of blood for SCD patients (www.haemmatch.org) which aims to reduce the harm caused by alloimmunisation. The pathway to delivery at a national level was challenging and included coordinating with multiple stakeholders: industry, government, healthcare and regulatory. However, it was highly collaborative and with meaningful public and patient involvement and engagement (PPIE), ensuring patient advocacy and voice were central to decision making. Transition for a research tool to a test that met clinically required standards was navigated and conducted through an international multi-centre pre-clinical study, which included the testing of 70,000 DNA samples from the National Institute for Health and Care Research (NIHR) BioResource STRIDES donor cohort (https://bioresource.nihr.ac.uk/) with the Axiom array. The DNA sample collection represented the five main genetic ancestry groups, with a total of 3530 DNA samples from Black people, with 62.9% and 37.1% being of African and Admixed American ancestry, respectively, and which included almost 600 Black people recruited into NIHR BioResource.

Several working groups, under joint leadership from NHSE and NHSBT were set up to facilitate and provide governance oversight to the deployment for the selected patient cohorts across the NHS. The high-level work plan included: Governance and Project management; Patient Recruitment and Referral; Information Governance; Operational and Digital Capability working groups. Within these groups were subject matter experts, NHSE/NHSBT representatives, hospital specialists, nurses, blood transfusion scientists, patients and charity representatives. NHSE/NHSBT from England worked with Scotland, Wales and Northern Ireland to ensure access to the test nationally. For successful engagement several communication tools were used. These included: webinars for patients and staff; patient facing website; staff facing website; direct communications to senior leadership in the NHS and hospital senior management; communications through Hospital Update; communications through the National Haemoglobinopathy Panel to the Haemoglobinopathy Coordinating Centres; information leaflets and an educational film tailored to patients; digital assets and posters (QR codes); patient stories and a communications plan (https://www.nhsbt.nhs.uk/what-we-do/clinical-and-research/blood-group-genotyping/). The work aligned with the NHSE Health Inequalities Programme.

To date 3890 samples have been referred to NHSBT from 103 hospitals from a population cohort of approximately 18,000. In conclusion, array genotyping for 56 HEA types has become available across the four nations of the United Kingdom to inform the more precise matching for HEA types between patients and donors. HLA typing results are used to determine whether SCD and thalassaemia patients are possibly eligible for curative treatment by stem cell transplantation or gene editing. Further attention is needed to complete test implementation and to maximise technological advances in blood typing at population scale.

Kaushikkar:Thermo Fisher: Current Employment. Ouwehand:Thermo Fisher: Consultancy. Lane:CareDx: Membership on an entity's Board of Directors or advisory committees; One Lambda: Membership on an entity's Board of Directors or advisory committees; Thermo Fisher Scientific: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Gleadall:Thermo Fisher: Consultancy.