{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T04:09:29Z","timestamp":1793765369907,"version":"4.6.1"},"reference-count":48,"publisher":"American Society of Hematology","issue":"14","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,4,4]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>There is significant ongoing debate regarding type 1 von Willebrand disease (VWD) defintion. Previous guidelines recommended patients with von Willebrand factor (VWF) levels &amp;lt;30 IU\/dL be diagnosed type 1 VWD, whereas patients with significant bleeding and VWF levels from 30 to 50 IU\/dL be diagnosed with low VWF. To elucidate the relationship between type 1 VWD and low VWF in the context of age-induced increases in VWF levels, we combined data sets from 2 national cohort studies: 162 patients with low VWF from the Low VWF in Ireland Cohort (LoVIC) and 403 patients with type 1 VWD from the Willebrand in The Netherlands (WiN) studies. In 47% of type 1 VWD participants, VWF levels remained &amp;lt;30 IU\/dL despite increasing age. Conversely, VWF levels increased to the low VWF range (30-50 IU\/dL) in 30% and normalized (&amp;gt;50 IU\/dL) in 23% of type 1 VWD cases. Crucially, absolute VWF antigen (VWF:Ag) levels and increase of VWF:Ag per year overlapped between low VWF and normalized type 1 VWD participants. Moreover, multiple regression analysis demonstrated that VWF:Ag levels in low VWF and normalized type 1 VWD patients would not have been different had they been diagnosed at the same age (\u03b2\u00a0= 0.00; 95% confidence interval,\u00a0\u22120.03 to 0.04). Consistently, no difference was found in the prevalence of VWF sequence variants; factor VIII activity\/VWF:Ag or VWF propeptide\/VWF:Ag ratios; or desmopressin responses between low VWF and normalized type 1 VWD patients. In conclusion, our findings demonstrate that low VWF does not constitute a discrete clinical or pathological entity. Rather, it is part of an age-dependent type 1 VWD evolving phenotype. Collectively, these data have important implications for future VWD classification criteria.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2023022457","type":"journal-article","created":{"date-parts":[[2023,12,24]],"date-time":"2023-12-24T13:07:19Z","timestamp":1703423239000},"page":"1414-1424","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":37,"title":["Type 1 VWD classification revisited: novel insights from combined analysis of the LoVIC and WiN studies"],"prefix":"10.1182","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3769-9148","authenticated-orcid":false,"given":"Ferdows","family":"Atiq","sequence":"first","affiliation":[{"name":"1Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland"},{"name":"2Department of Haematology, Erasmus University Medical Center-Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Blok","sequence":"additional","affiliation":[{"name":"2Department of Haematology, Erasmus University Medical Center-Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3822-1496","authenticated-orcid":false,"given":"Calvin B.","family":"van Kwawegen","sequence":"additional","affiliation":[{"name":"2Department of Haematology, Erasmus University Medical Center-Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9759-062X","authenticated-orcid":false,"given":"Dearbhla","family":"Doherty","sequence":"additional","affiliation":[{"name":"1Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland"},{"name":"3National Coagulation Centre, St James\u2019s Hospital, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2999-4216","authenticated-orcid":false,"given":"Michelle","family":"Lavin","sequence":"additional","affiliation":[{"name":"1Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland"},{"name":"3National Coagulation Centre, St James\u2019s Hospital, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9095-2475","authenticated-orcid":false,"given":"Johanna G.","family":"van der Bom","sequence":"additional","affiliation":[{"name":"4Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7005-5328","authenticated-orcid":false,"given":"Niamh M.","family":"O'Connell","sequence":"additional","affiliation":[{"name":"3National Coagulation Centre, St James\u2019s Hospital, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5241-4174","authenticated-orcid":false,"given":"Joke","family":"de Meris","sequence":"additional","affiliation":[{"name":"5Netherlands Hemophilia Society, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Ryan","sequence":"additional","affiliation":[{"name":"3National Coagulation Centre, St James\u2019s Hospital, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2423-2829","authenticated-orcid":false,"given":"Saskia E. M.","family":"Schols","sequence":"additional","affiliation":[{"name":"6Department of Hematology, Radboud University Medical Center, Nijmegen and Hemophilia Treatment Center, Nijmegen-Eindhoven-Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0214-1718","authenticated-orcid":false,"given":"Mary","family":"Byrne","sequence":"additional","affiliation":[{"name":"3National Coagulation Centre, St James\u2019s Hospital, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3281-926X","authenticated-orcid":false,"given":"Floor C. J. I.","family":"Heubel-Moenen","sequence":"additional","affiliation":[{"name":"7Department of Hematology, Maastricht University Medical Center, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3251-8595","authenticated-orcid":false,"given":"Karin P. M.","family":"van Galen","sequence":"additional","affiliation":[{"name":"8Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0108-4077","authenticated-orcid":false,"given":"Roger J. S.","family":"Preston","sequence":"additional","affiliation":[{"name":"1Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1557-2995","authenticated-orcid":false,"given":"Marjon H.","family":"Cnossen","sequence":"additional","affiliation":[{"name":"9Department of Pediatric Hematology and Oncology, Erasmus MC, University Medical Center\u2013Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0904-4360","authenticated-orcid":false,"given":"Karin","family":"Fijnvandraat","sequence":"additional","affiliation":[{"name":"10Department of Pediatric Hematology, Emma Children's Hospital, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2728-6788","authenticated-orcid":false,"given":"Ross I.","family":"Baker","sequence":"additional","affiliation":[{"name":"11Western Australia Centre for Thrombosis and Haemostasis, Perth Blood Institute, Murdoch University, Perth, WA, Australia"},{"name":"12Irish-Australian Blood Collaborative Network, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9447-0465","authenticated-orcid":false,"given":"Karina","family":"Meijer","sequence":"additional","affiliation":[{"name":"13Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4649-9014","authenticated-orcid":false,"given":"Paula","family":"James","sequence":"additional","affiliation":[{"name":"14Department of Medicine, Queen's University, Kingston, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1461-2871","authenticated-orcid":false,"given":"Jorge","family":"Di Paola","sequence":"additional","affiliation":[{"name":"15Department of Pediatrics, School of Medicine, Washington University in St. Louis, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3268-5759","authenticated-orcid":false,"given":"Jeroen","family":"Eikenboom","sequence":"additional","affiliation":[{"name":"16Department of Internal Medicine, Division of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5677-1371","authenticated-orcid":false,"given":"Frank W. 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