{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T03:12:09Z","timestamp":1785899529001,"version":"3.56.0"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,3,26]],"date-time":"2022-03-26T00:00:00Z","timestamp":1648252800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100001422","name":"American Society of Hematology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001422","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Von Willebrand Disease (VWD) is a common inherited bleeding disorder. Patients with VWD suffering from severe bleeding may benefit from the use of secondary long\u2010term prophylaxis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>Systematically summarize the evidence on the clinical outcomes of secondary long\u2010term prophylaxis in patients with VWD and severe recurrent bleedings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We searched Medline and EMBASE through October 2019 for relevant randomized clinical trials (RCTs) and comparative observational studies (OS) assessing the effects of secondary long\u2010term prophylaxis in patients with VWD. We used Cochrane Risk of Bias (RoB) tool and the RoB for Non\u2010Randomized Studies of interventions (ROBINS\u2010I) tool to assess the quality of the included studies. We conducted random\u2010effects meta\u2010analyses and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 12 studies. Evidence from one placebo controlled RCT suggested that VWD prophylaxis as compared to no prophylaxis reduced the rate of bleeding episodes (Rate ratio [RR], .24; 95% confidence interval [CI], .17\u2013.35; low certainty evidence), and of epistaxis (RR, .38; 95%CI, .21\u2013.67; moderate certainty evidence), and may increase serious adverse events RR 2.73 (95%CI .12\u201359.57; low certainty). Evidence from four before\u2010and\u2010after studies in which researchers reported comparative data suggested that VWD prophylaxis reduced the rate of bleeding (RR .34; 95%CI, .25\u2013.46; very low certainty evidence).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>VWD prophylaxis treatment seems to reduce the risk of spontaneous bleeding, epistaxis, and hospitalizations. More RCTs should be conducted to increase the certainty in these benefits.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14550","type":"journal-article","created":{"date-parts":[[2022,3,26]],"date-time":"2022-03-26T21:14:12Z","timestamp":1648329252000},"page":"373-387","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Outcomes of long\u2010term von Willebrand factor prophylaxis use in von Willebrand disease: A systematic literature review"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0211-715X","authenticated-orcid":false,"given":"Abdallah","family":"El Alayli","sequence":"first","affiliation":[{"name":"Outcomes and Implementation Research Unit Department of Internal Medicine University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romina","family":"Brignardello Petersen","sequence":"additional","affiliation":[{"name":"Department of Health Research Methods Evidence, and Impact McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nedaa M.","family":"Husainat","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine St. Mary's Hospital  Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad A.","family":"Kalot","sequence":"additional","affiliation":[{"name":"The State University of New York at Buffalo Department of Internal Medicine  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazan","family":"Aljabiri","sequence":"additional","affiliation":[{"name":"Lincoln Medical and Mental Health Center  The Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hani","family":"Turkmani","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alec","family":"Britt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein","family":"El\u2010Khechen","sequence":"additional","affiliation":[{"name":"Department of Health Research Methods Evidence, and Impact McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaneela","family":"Shahid","sequence":"additional","affiliation":[{"name":"Department of Health Research Methods Evidence, and Impact McMaster University  Hamilton Ontario Canada"},{"name":"Department of Pediatrics McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Roller","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahrzad","family":"Motaghi","sequence":"additional","affiliation":[{"name":"Department of Health Research Methods Evidence, and Impact McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razan","family":"Mansour","sequence":"additional","affiliation":[{"name":"Outcomes and Implementation Research Unit Department of Internal Medicine University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Tosetto","sequence":"additional","affiliation":[{"name":"Hemophilia and Thrombosis Center Hematology Department S. Bortolo Hospital  Vicenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2684-1006","authenticated-orcid":false,"given":"Rezan","family":"Abdul\u2010Kadir","sequence":"additional","affiliation":[{"name":"The Royal Free NHS Foundation Hospital and Institute for Women's Health University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8268-3268","authenticated-orcid":false,"given":"Michael","family":"Laffan","sequence":"additional","affiliation":[{"name":"Centre for Haematology Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2595-8541","authenticated-orcid":false,"given":"Angela","family":"Weyand","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology Oncology Department of Pediatrics University of Michigan Medical School  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5677-1371","authenticated-orcid":false,"given":"Frank W.G.","family":"Leebeek","sequence":"additional","affiliation":[{"name":"Department of Hematology Erasmus MC University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Arapshian","sequence":"additional","affiliation":[{"name":"Middle Village  New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kouides","sequence":"additional","affiliation":[{"name":"Mary M. 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