{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T02:44:43Z","timestamp":1785465883125,"version":"3.56.0"},"reference-count":86,"publisher":"American Society of Hematology","issue":"17","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,4,29]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>von Willebrand disease (VWD) is characterized by its heterogeneous clinical manifestation, which complicates its diagnosis and management. The clinical management of VWD has remained essentially unchanged over the last 30 years or so, using von Willebrand factor (VWF) concentrates, desmopressin, and anti\u2013fibrinolytic agents as main tools to control bleeding. This is in contrast to hemophilia A, for which a continuous innovative path has led to novel treatment modalities. Despite current VWD management being considered effective, quality-of-life studies consistently reveal a higher than anticipated burden of VWD on patients, which is particularly true for women. Apparently, despite our perceived notion of current therapeutic efficiency, there is space for innovation with the goal of reaching superior efficacy. Developing innovative treatments for VWD is complex, especially given the heterogeneity of the disease and the multifunctional nature of VWF. In this perspective article, we describe several potential strategies that could provide the basis for future VWD treatments. These include genetic approaches, such as gene therapy using dual-vector adenoassociated virus and transcriptional silencing of mutant alleles. Furthermore, protein-based approaches to increase factor FVIII levels in VWD-type 3 or 2N patients are discussed. Finally, antibody-based options to interfere with VWF degradation (for congenital VWD-type 2A or acquired von Willebrand syndrome-type 2A) or increase endogenous VWF levels (for VWD-type 1) are presented. By highlighting these potential strategies, we hope to initiate an innovative path, which ultimately would allow us to better serve VWD patients and their specific needs.<\/jats:p>","DOI":"10.1182\/blood.2020008501","type":"journal-article","created":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T22:13:43Z","timestamp":1614896023000},"page":"2299-2306","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":37,"title":["von Willebrand disease: what does the future hold?"],"prefix":"10.1182","volume":"137","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5152-9156","authenticated-orcid":false,"given":"C\u00e9cile V.","family":"Denis","sequence":"first","affiliation":[{"name":"Laboratory for Hemostasis, Inflammation & Thrombosis, Unit\u00e9 Mixed de Recherche S1176, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Universit\u00e9 Paris-Saclay, Le Kremlin-Bic\u00eatre, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5953-163X","authenticated-orcid":false,"given":"Sophie","family":"Susen","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unit\u00e9 1011, Institut Pasteur de Lille, Centre Hospitalier Universitaire de Lille, Universit\u00e9 de Lille, Lille, France; and"},{"name":"Hematology and Transfusion, Centre Hospitalier Universitaire de Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7937-3429","authenticated-orcid":false,"given":"Peter J.","family":"Lenting","sequence":"additional","affiliation":[{"name":"Laboratory for Hemostasis, Inflammation & Thrombosis, Unit\u00e9 Mixed de Recherche S1176, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Universit\u00e9 Paris-Saclay, Le Kremlin-Bic\u00eatre, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"21","key":"2021042912324581400_B1","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1056\/NEJMra1601561","article-title":"Von Willebrand\u2019s disease","volume":"375","author":"Leebeek","year":"2016","journal-title":"N Engl J Med"},{"issue":"2","key":"2021042912324581400_B2","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/j.1365-2516.2007.01643.x","article-title":"von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA)","volume":"14","author":"Nichols","year":"2008","journal-title":"Haemophilia"},{"issue":"2","key":"2021042912324581400_B3","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1055\/s-0037-1613992","article-title":"Impact, diagnosis and treatment of von Willebrand disease","volume":"84","author":"Sadler","year":"2000","journal-title":"Thromb Haemost"},{"issue":"4","key":"2021042912324581400_B4","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1111\/j.1365-2141.2000.02507.x","article-title":"Clinical manifestations and complications of childbirth and replacement therapy in 385 Iranian patients with type 3 von Willebrand disease","volume":"111","author":"Lak","year":"2000","journal-title":"Br J Haematol"},{"key":"2021042912324581400_B5","first-page":"1","article-title":"von Willebrand\u2019s disease in Sweden","volume":"238","author":"Silwer","year":"1973","journal-title":"Acta Paediatr Scand Suppl"},{"issue":"1","key":"2021042912324581400_B6","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1182\/bloodadvances.2020003265","article-title":"ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease","volume":"5","author":"James","year":"2021","journal-title":"Blood Adv"},{"issue":"1","key":"2021042912324581400_B7","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/rth2.12468","article-title":"Sexism in the management of bleeding disorders","volume":"5","author":"Weyand","year":"2020","journal-title":"Res Pract Thromb Haemost"},{"key":"2021042912324581400_B8","doi-asserted-by":"crossref","first-page":"100726","DOI":"10.1016\/j.eclinm.2021.100726","article-title":"Major differences in clinical presentation, diagnosis and management of men and women with autosomal inherited bleeding disorders","volume":"32","author":"Atiq","year":"2021","journal-title":"EClinicalMedicine"},{"issue":"4","key":"2021042912324581400_B9","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1046\/j.1365-2516.1998.440665.x","article-title":"Females with von Willebrand disease: 72 years as the silent majority","volume":"4","author":"Kouides","year":"1998","journal-title":"Haemophilia"},{"issue":"34","key":"2021042912324581400_B10","doi-asserted-by":"crossref","first-page":"8569","DOI":"10.1073\/pnas.1800097115","article-title":"Patient-physician gender concordance and increased mortality among female heart attack patients","volume":"115","author":"Greenwood","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"issue":"7","key":"2021042912324581400_B11","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1038\/embor.2012.87","article-title":"Sex and gender differences in health. 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