{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T11:13:39Z","timestamp":1781954019575,"version":"3.54.5"},"reference-count":29,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100011926","name":"EAHAD","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011926","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015438","name":"ISTH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015438","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012112","name":"Swedish Orphan Biovitrum","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012112","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011372","name":"RCPA Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011372","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jthjournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Thrombosis and Haemostasis"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1016\/j.jtha.2026.02.014","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T07:51:49Z","timestamp":1772610709000},"page":"2096-2102","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prothrombotic PROC variant rebalancing hemostasis in severe hemophilia A with attenuated bleeding risk"],"prefix":"10.1016","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5539-0673","authenticated-orcid":false,"given":"Radha","family":"Ramanan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quentin","family":"Van Thillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud","family":"Lavend\u2019homme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Van Laer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Thys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koenraad","family":"De Wispelaere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarissa","family":"Baert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrielle","family":"Kint","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Verhamme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Vanassche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"McFadyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C.","family":"Perkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huyen A.","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerle","family":"Labarque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Jacquemin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Freson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jtha.2026.02.014_bib1","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1111\/jth.12672","article-title":"Factor IX and Rare Coagulation Disorders of the Scientific and Standardization Committee of the International Society on Thrombosis and Hemostasis. Definitions in hemophilia: communication from the SSC of the ISTH","volume":"12","author":"Blanchette","year":"2014","journal-title":"J Thromb Haemost"},{"key":"10.1016\/j.jtha.2026.02.014_bib2","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1055\/s-0029-1222609","article-title":"Interpatient phenotypic inconsistency in severe congenital hemophilia: a systematic review of the role of inherited thrombophilia","volume":"35","author":"Franchini","year":"2009","journal-title":"Semin Thromb Hemost"},{"key":"10.1016\/j.jtha.2026.02.014_bib3","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1111\/j.1365-2141.2007.06693.x","article-title":"Contribution of natural anticoagulant and fibrinolytic factors in modulating the clinical severity of haemophilia patients","volume":"138","author":"Shetty","year":"2007","journal-title":"Br J Haematol"},{"key":"10.1016\/j.jtha.2026.02.014_bib4","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1182\/blood.V90.8.3067","article-title":"An in vitro analysis of the combination of hemophilia A and factor V(LEIDEN)","volume":"90","author":"van \u2019t Veer","year":"1997","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2026.02.014_bib5","first-page":"2902","article-title":"Rebalancing agents in hemophilia: knowns, unknowns, and uncertainties","volume":"110","author":"Van Thillo","year":"2025","journal-title":"Haematologica"},{"key":"10.1016\/j.jtha.2026.02.014_bib6","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/S0021-9258(17)33886-3","article-title":"A new vitamin K-dependent protein. Purification from bovine plasma and preliminary characterization","volume":"251","author":"Stenflo","year":"1976","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jtha.2026.02.014_bib7","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1182\/blood.V59.5.1067.1067","article-title":"Mechanism of action of human activated protein C, a thrombin-dependent anticoagulant enzyme","volume":"59","author":"Marlar","year":"1982","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2026.02.014_bib8","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1172\/JCI110385","article-title":"Deficiency of protein C in congenital thrombotic disease","volume":"68","author":"Griffin","year":"1981","journal-title":"J Clin Invest"},{"key":"10.1016\/j.jtha.2026.02.014_bib9","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1182\/blood.V124.21.583.583","article-title":"Impact of SERPINC1, PROC and PROS1 mutations on the thrombotic phenotype in children with venous thromboembolism: an observational multicenter cohort study","volume":"124","author":"Limperger","year":"2014","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2026.02.014_bib10","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.jtha.2022.12.007","article-title":"Clinical application of multigene panel testing for bleeding, thrombotic, and platelet disorders: a 3-year Belgian experience","volume":"21","author":"Van Laer","year":"2023","journal-title":"J Thromb Haemost"},{"key":"10.1016\/j.jtha.2026.02.014_bib11","first-page":"405","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med Off J Am Coll Med Genet"},{"key":"10.1016\/j.jtha.2026.02.014_bib12","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"10.1016\/j.jtha.2026.02.014_bib15","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1046\/j.1365-2516.2002.00686.x","article-title":"Paradoxical hyperfibrinolysis is associated with a more intensely haemorrhagic phenotype in severe congenital haemophilia","volume":"8","author":"Gr\u00fcnewald","year":"2002","journal-title":"Haemoph Off J World Fed Hemoph"},{"key":"10.1016\/j.jtha.2026.02.014_bib16","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1160\/TH04-02-0112","article-title":"Do prothrombotic factors influence clinical phenotype of severe haemophilia? A review of the literature","volume":"92","author":"van Dijk","year":"2004","journal-title":"Thromb Haemost"},{"key":"10.1016\/j.jtha.2026.02.014_bib17","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.thromres.2017.05.038","article-title":"Modifiers of clinical phenotype in severe congenital hemophilia","volume":"156","author":"Franchini","year":"2017","journal-title":"Thromb Res"},{"key":"10.1016\/j.jtha.2026.02.014_bib18","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1055\/s-0037-1613824","article-title":"Effect of the factor V Leiden mutation on the clinical expression of severe hemophilia A","volume":"83","author":"Lee","year":"2000","journal-title":"Thromb Haemost"},{"key":"10.1016\/j.jtha.2026.02.014_bib19","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0049-3848(03)00144-0","article-title":"Does the MTHFR 677T allele alter the clinical phenotype in severe haemophilia A?","volume":"109","author":"Ahmed","year":"2003","journal-title":"Thromb Res"},{"key":"10.1016\/j.jtha.2026.02.014_bib20","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1055\/s-0038-1649922","article-title":"Low prevalence of the factor V Leiden mutation among \u201csevere\u201d hemophiliacs with a \u201cmilder\u201d bleeding diathesis","volume":"74","author":"Arbini","year":"1995","journal-title":"Thromb Haemost"},{"key":"10.1016\/j.jtha.2026.02.014_bib21","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1182\/blood.V88.4.1183.bloodjournal8841183","article-title":"Moderation of hemophilia A phenotype by the factor V R506Q mutation","volume":"88","author":"Nichols","year":"1996","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2026.02.014_bib22","first-page":"279","article-title":"The prothrombin 20210A allele influences clinical manifestations of hemophilia A in patients with intron 22 inversion and without inhibitors","volume":"87","author":"Tizzano","year":"2002","journal-title":"Haematologica"},{"key":"10.1016\/j.jtha.2026.02.014_bib23","doi-asserted-by":"crossref","first-page":"e322","DOI":"10.1016\/S2352-3026(23)00037-6","article-title":"Fitusiran prophylaxis in people with severe haemophilia A or haemophilia B without inhibitors (ATLAS-A\/B): a multicentre, open-label, randomised, phase 3 trial","volume":"10","author":"Srivastava","year":"2023","journal-title":"Lancet Haematol"},{"key":"10.1016\/j.jtha.2026.02.014_bib24","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/S0140-6736(23)00284-2","article-title":"Efficacy and safety of fitusiran prophylaxis in people with haemophilia A or haemophilia B with inhibitors (ATLAS-INH): a multicentre, open-label, randomised phase 3 trial","volume":"401","author":"Young","year":"2023","journal-title":"Lancet"},{"key":"10.1016\/j.jtha.2026.02.014_bib25","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1182\/blood.2023021864","article-title":"Fitusiran prophylaxis in people with hemophilia A or B who switched from prior BPA\/CFC prophylaxis: the ATLAS-PPX trial","volume":"143","author":"Kenet","year":"2024","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2026.02.014_bib26","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1056\/NEJMoa2216455","article-title":"Phase 3 trial of concizumab in hemophilia with inhibitors","volume":"389","author":"Matsushita","year":"2023","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jtha.2026.02.014_bib27","doi-asserted-by":"crossref","first-page":"e891","DOI":"10.1016\/S2352-3026(24)00307-7","article-title":"Concizumab prophylaxis in people with haemophilia A or haemophilia B without inhibitors (explorer8): a prospective, multicentre, open-label, randomised, phase 3a trial","volume":"11","author":"Chowdary","year":"2024","journal-title":"Lancet Haematol"},{"issue":"Suppl 1","key":"10.1016\/j.jtha.2026.02.014_bib28","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1182\/blood-2023-181263","article-title":"Efficacy and safety of the anti-tissue factor pathway inhibitor marstacimab in participants with severe hemophilia without inhibitors: results from the phase 3 Basis trial","volume":"142","author":"Matino","year":"2023","journal-title":"Blood"},{"issue":"Suppl 1","key":"10.1016\/j.jtha.2026.02.014_bib29","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1182\/blood-2022-170245","article-title":"Pre-clinical characterization of VGA039, an anti-protein S monoclonal antibody being developed as a universal hemostatic agent for various bleeding disorders","volume":"140","author":"Leong","year":"2022","journal-title":"Blood"},{"issue":"Suppl 1","key":"10.1016\/j.jtha.2026.02.014_bib30","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1182\/blood-2022-159631","article-title":"Serpinpc in persons with severe hemophilia (PwH): updated results from a multi-center, multi-part, first-in-human study","volume":"140","author":"Baglin","year":"2022","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2026.02.014_bib31","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1182\/bloodadvances.2024015201","article-title":"The preclinical profile of SerpinPC: a potential new treatment for hemophilia","volume":"9","author":"Huntington","year":"2025","journal-title":"Blood Adv"}],"container-title":["Journal of Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1538783626001315?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1538783626001315?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T12:04:13Z","timestamp":1780574653000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1538783626001315"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":29,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["S1538783626001315"],"URL":"https:\/\/doi.org\/10.1016\/j.jtha.2026.02.014","relation":{},"ISSN":["1538-7836"],"issn-type":[{"value":"1538-7836","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Prothrombotic PROC variant rebalancing hemostasis in severe hemophilia A with attenuated bleeding risk","name":"articletitle","label":"Article Title"},{"value":"Journal of Thrombosis and Haemostasis","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jtha.2026.02.014","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}]}}