{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T19:24:17Z","timestamp":1776453857784,"version":"3.51.2"},"reference-count":124,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T00:00:00Z","timestamp":1702598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIHR Imperial Biomedical Research Centre"},{"name":"National Institute for Health Research (NIHR)"},{"name":"NHS England"},{"name":"Cancer Research UK"},{"name":"Medical Research Council"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Hereditary haemorrhagic telangiectasia (HHT) is a vascular dysplasia that commonly results in bleeding but with frequent indications for therapeutic anticoagulation. Our aims were to advance the understanding of drug-specific intolerance and evaluate if there was an indication for pharmacogenomic testing. Genes encoding proteins involved in the absorption, distribution, metabolism, and excretion of warfarin, heparin, and direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran were identified and examined. Linkage disequilibrium with HHT genes was excluded, before variants within these genes were examined following whole genome sequencing of general and HHT populations. The 44 genes identified included 5\/17 actionable pharmacogenes with guidelines. The 76,156 participants in the Genome Aggregation Database v3.1.2 had 28,446 variants, including 9668 missense substitutions and 1076 predicted loss-of-function (frameshift, nonsense, and consensus splice site) variants, i.e., approximately 1 in 7.9 individuals had a missense substitution, and 1 in 71 had a loss-of-function variant. Focusing on the 17 genes relevant to usually preferred DOACs, similar variant profiles were identified in HHT patients. With HHT patients at particular risk of haemorrhage when undergoing anticoagulant treatment, we explore how pre-emptive pharmacogenomic testing, alongside HHT gene testing, may prove beneficial in reducing the risk of bleeding and conclude that HHT patients are well placed to be at the vanguard of personalised prescribing.<\/jats:p>","DOI":"10.3390\/jcm12247710","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T11:26:52Z","timestamp":1702639612000},"page":"7710","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pharmacogenomic Considerations for Anticoagulant Prescription in Patients with Hereditary Haemorrhagic Telangiectasia"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5072-2229","authenticated-orcid":false,"given":"Sarah","family":"McCarley","sequence":"first","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London W12 0NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Murphy","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Imperial College Healthcare NHS Trust, London W2 1NY, UK"},{"name":"Social, Genetic and Environmental Determinants of Health Theme, NIHR Imperial Biomedical Research Centre, London W2 1NY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack","family":"Thompson","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London W12 0NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9007-5775","authenticated-orcid":false,"given":"Claire","family":"Shovlin","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London W12 0NN, UK"},{"name":"Social, Genetic and Environmental Determinants of Health Theme, NIHR Imperial Biomedical Research Centre, London W2 1NY, UK"},{"name":"Specialist Medicine, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London W12 0HS, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/ng1294-345","article-title":"Endoglin, a TGF-\u03b2 binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1","volume":"8","author":"McAllister","year":"1994","journal-title":"Nat. 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