{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:30:42Z","timestamp":1790501442537,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,8]],"date-time":"2017-11-08T00:00:00Z","timestamp":1510099200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"MURST","award":["60%, 2013"],"award-info":[{"award-number":["60%, 2013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2018,1]]},"abstract":"Introduction<\/jats:title>An abnormal factor VIII<\/jats:styled-content> (FVIII<\/jats:styled-content>) binding capacity of von Willebrand factor (VWF<\/jats:styled-content>) identifies type 2N von Willebrand disease (VWD<\/jats:styled-content>). Type 2N VWD<\/jats:styled-content> patients are identified by means of the VWF FVIII<\/jats:styled-content> binding (VWF<\/jats:styled-content>:FVIIIB<\/jats:styled-content>) assay, and especially their VWF<\/jats:styled-content>:FVIIIB<\/jats:styled-content>\/VWF<\/jats:styled-content>:Ag ratio (VWF<\/jats:styled-content>:FVIIIB<\/jats:styled-content> ratio).<\/jats:p><\/jats:sec>Aim<\/jats:title>We report on our 15\u2010year experience of diagnosing type 2N VWD<\/jats:styled-content>.<\/jats:p><\/jats:sec>Methods<\/jats:title>We have performed 2178 VWF<\/jats:styled-content>:FVIIIB<\/jats:styled-content> assays in bleeders and normal subjects.<\/jats:p><\/jats:sec>Results<\/jats:title>von Willebrand factor (VWF<\/jats:styled-content>):FVIIIB<\/jats:styled-content> was reduced in 682, but only 60 had low VWF<\/jats:styled-content>:FVIIIB<\/jats:styled-content> ratios (<0.74). Among nine patients who had a VWF<\/jats:styled-content>:FVIIIB<\/jats:styled-content> ratio below 0.3, four had normal VWF<\/jats:styled-content> levels and were homozygotes for the p.R854Q mutation; the other five had low VWF<\/jats:styled-content> levels due to a quantitative VWF<\/jats:styled-content> mutation combined with p.R854Q. The VWF<\/jats:styled-content>:FVIIIB<\/jats:styled-content> ratio ranged between 0.3 and 0.73 in 51 subjects; 34 of them were heterozygotes for the p.R854Q mutation, while one carried the p.R760C. The heterozygotes for type 2N included subjects with or without bleeding symptoms, the former with significantly lower mean VWF<\/jats:styled-content> levels than the latter. Among the 116 normal subjects tested, six were heterozygotes for the p.R854Q mutation (all asymptomatic).<\/jats:p><\/jats:sec>Conclusions<\/jats:title>The prevalence of type 2N in our VWD<\/jats:styled-content> cohort was 2.5%, and 5.2% of the general population in Northeast Italy was found heterozygous for the p.R854Q mutation. It might be difficult to reveal a type 2N defect using routine tests alone, especially when it is combined with a quantitative VWF<\/jats:styled-content> mutation. Accordingly, we always recommend VWF<\/jats:styled-content>:FVIIIB<\/jats:styled-content> assay in the diagnostic workup of VWD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.13366","type":"journal-article","created":{"date-parts":[[2017,11,8]],"date-time":"2017-11-08T08:50:46Z","timestamp":1510131046000},"page":"134-140","source":"Crossref","is-referenced-by-count":32,"title":["Type 2N von Willebrand disease: Characterization and diagnostic difficulties"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6556-5967","authenticated-orcid":false,"given":"A.","family":"Casonato","sequence":"first","affiliation":[{"name":"Department of Medicine Hemorrhagic and Thrombotic Disorders Unit University of Padua Medical School Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Galletta","sequence":"additional","affiliation":[{"name":"Department of Medicine Hemorrhagic and Thrombotic Disorders Unit University of Padua Medical School Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Sarolo","sequence":"additional","affiliation":[{"name":"Department of Medicine Hemorrhagic and Thrombotic Disorders Unit University of Padua Medical School Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Daidone","sequence":"additional","affiliation":[{"name":"Department of Medicine Hemorrhagic and Thrombotic Disorders Unit University of Padua Medical School Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.67.1.395"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1016\/S0021-9258(18)52225-0","article-title":"Von Willebrand factor mediates protection of FVIII from activated protein C\u2010catalyzed 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