{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:27:30Z","timestamp":1787502450847,"version":"build-2736575974"},"reference-count":33,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"vor","delay-in-days":59,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012028","name":"Trombosestichting Nederland","doi-asserted-by":"publisher","award":["TSN2015\u20102"],"award-info":[{"award-number":["TSN2015\u20102"]}],"id":[{"id":"10.13039\/501100012028","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 HL\u2010139420"],"award-info":[{"award-number":["P01 HL\u2010139420"]}],"id":[{"id":"10.13039\/100000002","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":[[2022,2]]},"DOI":"10.1111\/jth.15589","type":"journal-article","created":{"date-parts":[[2021,11,13]],"date-time":"2021-11-13T03:54:45Z","timestamp":1636775685000},"page":"328-338","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":8,"title":["Major bleeding during oral anticoagulant therapy associated with factor V activation by factor Xa"],"prefix":"10.1016","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9398-9094","authenticated-orcid":false,"given":"Anja","family":"Maag","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9201-401X","authenticated-orcid":false,"given":"Nienke","family":"van Rein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim J.","family":"Schuijt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wil F.","family":"Kopatz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Kruijswijk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Thomassen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilman M.","family":"Hackeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodney M.","family":"Camire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"van der Poll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4198-6780","authenticated-orcid":false,"given":"Joost C.M.","family":"Meijers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mettine H.A.","family":"Bos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelis","family":"van \u2019t Veer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1111\/jth.15589_bb0010","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.blre.2013.02.004","article-title":"Bleeding risks associated with vitamin K antagonists","volume":"27","author":"Linkins","year":"2013","journal-title":"Blood Rev"},{"key":"10.1111\/jth.15589_bb0015","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1055\/s-0037-1598061","article-title":"Scoring systems for estimating the risk of anticoagulant\u2010associated bleeding","volume":"43","author":"Parks","year":"2017","journal-title":"Semin Thromb Hemost"},{"key":"10.1111\/jth.15589_bb0020","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0176967","article-title":"Prediction of bleeding risk in patients taking vitamin K antagonists using thrombin generation testing","volume":"12","author":"Bloemen","year":"2017","journal-title":"PLoS One"},{"key":"10.1111\/jth.15589_bb0025","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1001\/archinternmed.2009.170","article-title":"Thrombomodulin as a marker for bleeding complications during warfarin treatment","volume":"169","author":"Lind","year":"2009","journal-title":"Arch Intern Med"},{"key":"10.1111\/jth.15589_bb0030","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1146\/annurev.bi.57.070188.004411","article-title":"Cofactor proteins in the assembly and expression of blood clotting enzyme complexes","volume":"57","author":"Mann","year":"1988","journal-title":"Annu Rev Biochem"},{"key":"10.1111\/jth.15589_bb0035","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/S0021-9258(19)86294-4","article-title":"The role of phospholipids and factor Va in the prothrombinase complex","volume":"255","author":"Rosing","year":"1980","journal-title":"J Biol Chem"},{"key":"10.1111\/jth.15589_bb0040","doi-asserted-by":"crossref","first-page":"5260","DOI":"10.1073\/pnas.74.12.5260","article-title":"Activation of factor IX by the reaction product of tissue factor and factor VII: additional pathway for initiating blood coagulation","volume":"74","author":"Osterud","year":"1977","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1111\/jth.15589_bb0045","doi-asserted-by":"crossref","first-page":"19580","DOI":"10.1074\/jbc.M400727200","article-title":"The factor V activation paradox","volume":"279","author":"Orfeo","year":"2004","journal-title":"J Biol Chem"},{"key":"10.1111\/jth.15589_bb0050","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1161\/CIRCULATIONAHA.113.003191","article-title":"Factor Xa activation of factor V is of paramount importance in initiating the coagulation system: lessons from a tick salivary protein","volume":"128","author":"Schuijt","year":"2013","journal-title":"Circulation"},{"issue":"7","key":"10.1111\/jth.15589_bb0055","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1111\/jth.15329","article-title":"Structure\u2010function of anticoagulant TIX\u20105, the inhibitor of factor Xa\u2010mediated FV activation","volume":"19","author":"Maag","year":"2021","journal-title":"J Thromb Haemost"},{"key":"10.1111\/jth.15589_bb0060","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1111\/jth.12354","article-title":"Inhibition of thrombin\u2010mediated factor V activation contributes to the anticoagulant activity of fibrinogen \u03b3\u2032","volume":"11","author":"Omarova","year":"2013","journal-title":"J Thromb Haemost"},{"key":"10.1111\/jth.15589_bb0065","doi-asserted-by":"crossref","first-page":"3106","DOI":"10.1073\/pnas.0504240103","article-title":"Protein S stimulates inhibition of the tissue factor pathway by tissue factor pathway inhibitor","volume":"103","author":"Hackeng","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1111\/jth.15589_bb0070","doi-asserted-by":"crossref","first-page":"17838","DOI":"10.1073\/pnas.1310444110","article-title":"Tissue factor pathway inhibitor\u2010alpha inhibits prothrombinase during the initiation of blood coagulation","volume":"110","author":"Wood","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1111\/jth.15589_bb0075","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1111\/jth.13665","article-title":"Novel insights into the regulation of coagulation by factor V isoforms, tissue factor pathway inhibitor \u03b1, and protein S","volume":"15","author":"Dahlb\u00e4ck","year":"2017","journal-title":"J Thromb Haemost"},{"key":"10.1111\/jth.15589_bb0080","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/jth.13559","article-title":"The C\u2010terminus of tissue factor pathway inhibitor\u2010\u03b1 inhibits factor V activation by protecting the Arg1545 cleavage site","volume":"15","author":"van Doorn","year":"2017","journal-title":"J Thromb Haemost"},{"key":"10.1111\/jth.15589_bb0085","doi-asserted-by":"crossref","first-page":"100234","DOI":"10.1074\/jbc.RA120.016341","article-title":"Regulation of factor V and factor V\u2010short by TFPI\u03b1: Relationship between B\u2010domain proteolysis and binding","volume":"296","author":"Petrillo","year":"2021","journal-title":"J Biol Chem"},{"key":"10.1111\/jth.15589_bb0090","doi-asserted-by":"crossref","first-page":"3777","DOI":"10.1172\/JCI69091","article-title":"Coagulation factor VA2440G causes east Texas bleeding disorder via TFPI\u03b1","volume":"123","author":"Vincent","year":"2013","journal-title":"J Clin Invest"},{"key":"10.1111\/jth.15589_bb0095","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/rth2.12057","article-title":"Factor V\u2010short and protein S as synergistic tissue factor pathway inhibitor (TFPI\u03b1) cofactors","volume":"2","author":"Dahlb\u00e4ck","year":"2018","journal-title":"Res Pract Thromb Haemost"},{"key":"10.1111\/jth.15589_bb0100","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1046\/j.1538-7836.2003.00298.x","article-title":"What is all that thrombin for?","volume":"1","author":"Mann","year":"2003","journal-title":"J Thromb Haemost"},{"key":"10.1111\/jth.15589_bb0105","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0164485","article-title":"Objectives and design of Bleeds: a cohort study to identify new risk factors and predictors for major bleeding during treatment with vitamin K antagonists","volume":"11","author":"van Rein","year":"2016","journal-title":"PLoS One"},{"key":"10.1111\/jth.15589_bb0110","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1111\/j.1538-7836.2010.04016.x","article-title":"Intracranial and fatal bleeding according to indication for long\u2010term oral anticoagulant therapy: major bleeds according to indication for anticoagulation","volume":"8","author":"Linkins","year":"2010","journal-title":"J Thromb Haemost"},{"key":"10.1111\/jth.15589_bb0115","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/sim.4780070127","article-title":"Aspects of the use of relative risk models in the design and analysis of cohort studies and prevention trials","volume":"7","author":"Prentice","year":"1988","journal-title":"Stat Med"},{"key":"10.1111\/jth.15589_bb0120","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1159\/000073575","article-title":"The calibrated automated thrombogram (CAT): a universal routine test for hyper\u2010 and hypocoagulability","volume":"32","author":"Hemker","year":"2002","journal-title":"Pathophysiol Haemost Thromb"},{"key":"10.1111\/jth.15589_bb0125","first-page":"547","article-title":"Thrombin generation assessed as endogenous thrombin potential in patients with hyper\u2010 or hypo\u2010coagulability","volume":"88","author":"Chantarangkul","year":"2003","journal-title":"Haematologica"},{"key":"10.1111\/jth.15589_bb0130","doi-asserted-by":"crossref","first-page":"26342","DOI":"10.1074\/jbc.M112.377168","article-title":"A bipartite autoinhibitory region within the B\u2010domain suppresses function in factor V","volume":"287","author":"Bos","year":"2012","journal-title":"J Biol Chem"},{"key":"10.1111\/jth.15589_bb0135","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1111\/j.1538-7836.2010.03743.x","article-title":"Thrombin generation\u2010based assays to measure the activity of the TFPI\u2010protein S pathway in plasma from normal and protein S\u2010deficient individuals","volume":"8","author":"Maurissen","year":"2010","journal-title":"J Thromb Haemost"},{"key":"10.1111\/jth.15589_bb0140","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/j.thromres.2014.09.008","article-title":"Changes in haemostatic parameters during the menstrual cycle and subsequent use of drospirenone\u2010containing oral contraceptives","volume":"134","author":"Tchaikovski","year":"2014","journal-title":"Thromb Res"},{"key":"10.1111\/jth.15589_bb0145","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1182\/blood-2014-08-592733","article-title":"A novel mutation in the F5 gene (factor V Amsterdam) associated with bleeding independent of factor V procoagulant function","volume":"125","author":"Cunha","year":"2015","journal-title":"Blood"},{"key":"10.1111\/jth.15589_bb0150","first-page":"e291","article-title":"Calibrated automated thrombinography (CAT), a tool to identify patients at risk of bleeding during anticoagulant therapy: a systematic review. TH open companion","volume":"2","author":"Zwaveling","year":"2018","journal-title":"J Thromb Haemost"},{"key":"10.1111\/jth.15589_bb0155","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1055\/a-1200-0417","article-title":"Usefulness of thrombin generation","volume":"40","author":"Tripodi","year":"2020","journal-title":"H\u00e4mostaseologie"},{"key":"10.1111\/jth.15589_bb0160","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1111\/ijlh.13638","article-title":"Thrombin generation abnormalities in commonly encountered platelet function disorders","volume":"43","author":"Sharma","year":"2021","journal-title":"Int J Lab Hematol"},{"key":"10.1111\/jth.15589_bb0165","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1111\/jth.14529","article-title":"Thrombin\u2010generating potential, plasma clot formation, and clot lysis are impaired in patients with bleeding of unknown cause","volume":"17","author":"Hofer","year":"2019","journal-title":"J Thromb Haemost"},{"key":"10.1111\/jth.15589_bb0170","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1161\/CIRCEP.111.967000","article-title":"Relation of the HAS\u2010BLED bleeding risk score to major bleeding, cardiovascular events, and mortality in anticoagulated patients with atrial fibrillation","volume":"5","author":"Morrone","year":"2012","journal-title":"Circ Arrhythm Electrophysiol"}],"container-title":["Journal of Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jth.15589","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jth.15589","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1538783622028082?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1538783622028082?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jth.15589","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T03:34:34Z","timestamp":1761536074000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1538783622028082"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["S1538783622028082"],"URL":"https:\/\/doi.org\/10.1111\/jth.15589","relation":{},"ISSN":["1538-7836"],"issn-type":[{"value":"1538-7836","type":"print"}],"subject":[],"published":{"date-parts":[[2022,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Major bleeding during oral anticoagulant therapy associated with factor V activation by factor Xa","name":"articletitle","label":"Article Title"},{"value":"Journal of Thrombosis and Haemostasis","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1111\/jth.15589","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2021 The Authors. Journal of Thrombosis and Haemostasis published by ELSEVIER INC. on behalf of International Society on Thrombosis and Haemostasis","name":"copyright","label":"Copyright"}]}}