{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T06:46:54Z","timestamp":1780382814351,"version":"3.54.1"},"reference-count":13,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,2,4]],"date-time":"2016-02-04T00:00:00Z","timestamp":1454544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2016,7]]},"abstract":"Introduction<\/jats:title>von Willebrand disease (VWD<\/jats:styled-content>) is the most common inherited bleeding disorder. The age of bleeding onset is highly variable, also in patients with similar degree of severity.<\/jats:p><\/jats:sec>Aim<\/jats:title>The primary aim of this study was to evaluate whether baseline factor VIII<\/jats:styled-content> (FVIII<\/jats:styled-content>) plasma levels correlate with age at first bleeding in patients with extremely low levels of VWF<\/jats:styled-content>:RC<\/jats:styled-content>o (<6 IU dL\u22121<\/jats:sup>).<\/jats:p><\/jats:sec>Methods<\/jats:title>One hundred and three patients with VWF<\/jats:styled-content>:RC<\/jats:styled-content>o <6 IU dL\u22121<\/jats:sup> (6 VWD<\/jats:styled-content>1, 73 VWD<\/jats:styled-content>2 and 24 VWD<\/jats:styled-content>3) undergoing a medical examination between September 2010 and September 2013 were included. The relationship between baseline FVIII<\/jats:styled-content> levels and age at first bleeding was tested in a multivariable linear regression model, adjusting for sex.<\/jats:p><\/jats:sec>Results<\/jats:title>The median age at first bleeding was lower in patients with VWD<\/jats:styled-content>3 than in those with severe forms of VWD<\/jats:styled-content>1 or VWD<\/jats:styled-content>2 (1 year vs. 7 and 8 years, respectively, P<\/jats:italic> < 0.0001). A positive non\u2010linear relationship between FVIII<\/jats:styled-content> levels and age at first bleeding was found, the latter increasing by 5 years for every 10 IU dL\u22121<\/jats:sup> increase of FVIII<\/jats:styled-content> (\u03b2 = 4.95 [95% CI<\/jats:styled-content>: 2.02\u20137.87]) until levels of 30 IU dL\u22121<\/jats:sup>, after which the age increased slowly. This relationship was not found in VWD<\/jats:styled-content> 2A and 2B. In 65 patients (63%) there was a more than 6\u2010month delay between bleeding onset and VWD<\/jats:styled-content> diagnosis, with no difference over decades.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Baseline FVIII<\/jats:styled-content> plasma levels influence the age at bleeding onset in VWD<\/jats:styled-content> patients with extremely low levels of VWF<\/jats:styled-content>:RC<\/jats:styled-content>o, except in those with types 2A and 2B.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.12900","type":"journal-article","created":{"date-parts":[[2016,2,4]],"date-time":"2016-02-04T08:01:36Z","timestamp":1454572896000},"page":"564-569","source":"Crossref","is-referenced-by-count":7,"title":["Baseline factor VIII<\/scp> plasma levels and age at first bleeding in patients with severe forms of von Willebrand disease"],"prefix":"10.1111","volume":"22","author":[{"given":"S. M.","family":"Siboni","sequence":"first","affiliation":[{"name":"Angelo Bianchi Bonomi Hemophilia and Thrombosis Center Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico and University of Milan Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Biguzzi","sequence":"additional","affiliation":[{"name":"Angelo Bianchi Bonomi Hemophilia and Thrombosis Center Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico and University of Milan Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Caiani","sequence":"additional","affiliation":[{"name":"Angelo Bianchi Bonomi Hemophilia and Thrombosis Center Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico and University of Milan Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Mistretta","sequence":"additional","affiliation":[{"name":"Angelo Bianchi Bonomi Hemophilia and Thrombosis Center Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico and University of Milan Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Bucciarelli","sequence":"additional","affiliation":[{"name":"Angelo Bianchi Bonomi Hemophilia and Thrombosis Center Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico and University of Milan Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Peyvandi","sequence":"additional","affiliation":[{"name":"Angelo Bianchi Bonomi Hemophilia and Thrombosis Center Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico and University of Milan Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,2,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781444306286.ch8"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2006.02146.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-06-498303"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2000.02507.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2004.00991.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2007.01643.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2012.04661.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-04-152280"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH10-11-0697"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-02-557264"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2012.077263"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-947863"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12064"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhae.12900","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.12900","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T23:38:37Z","timestamp":1695512317000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.12900"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,4]]},"references-count":13,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,7]]}},"alternative-id":["10.1111\/hae.12900"],"URL":"https:\/\/doi.org\/10.1111\/hae.12900","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,4]]}}}