{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T14:19:55Z","timestamp":1785593995238,"version":"3.56.0"},"reference-count":47,"publisher":"American Society of Hematology","issue":"3","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7,17]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Previous reports have highlighted that some patients with low von Willebrand factor (VWF) with significant bleeding were diagnosed based on an isolated but persistent reduction in plasma VWF activity levels in the 30 to 50 IU\/dL range. These patients had plasma VWF antigen (VWF:Ag) levels &amp;gt;50 IU\/dL and thus had qualitative low VWF (low VWF\u2013QL) rather than quantitative low VWF. Although the clinical importance of functional VWF defects in type 2 von Willebrand disease (VWD) is well recognized, the translational implications of mild functional defects in patients with low VWF\u2013QL have not been defined. To address this clinically important question, we combined low VWF data sets from the low VWF in Ireland cohort and the low VWF in Erasmus MC studies. Overall, we observed that low VWF\u2013QL was common and accounted for \u223c50% of our combined low VWF cohort. Importantly, our findings demonstrated that many of these patients with mild isolated functional VWF defects in the 30 to 50 IU\/dL range had significant bleeding phenotypes, although their plasma VWF:Ag levels were within the normal range. In addition, we further showed that low VWF\u2013QL is a distinct clinicopathological entity compared to type 2 VWD. Finally, our studies highlighted that low VWF\u2013QL is predominantly caused by abnormalities in VWF biosynthesis within endothelial cells that are occurring largely independent of identifiable pathological VWF sequence variants. Cumulatively, these novel observations have important clinical implications for the diagnosis and management of patients with mild functional VWF defects.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2024028035","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T15:34:13Z","timestamp":1745595253000},"page":"369-381","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":4,"title":["Clinical phenotype and pathophysiological mechanisms underlying qualitative low VWF"],"prefix":"10.1182","volume":"146","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\/0000-0001-9688-2324","authenticated-orcid":false,"given":"Anne-Marije","family":"Hulshof","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\/0000-0002-9759-062X","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\u2019Connell","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. 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