{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:04:48Z","timestamp":1790687088052,"version":"4.1.0"},"reference-count":13,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,7,17]],"date-time":"2014-07-17T00:00:00Z","timestamp":1405555200000},"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":[[2014,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The objective of this study was to evaluate the inhibitor development (<jats:styled-content style=\"fixed-case\">ID<\/jats:styled-content>) in previously untreated patients (<jats:styled-content style=\"fixed-case\">PUP<\/jats:styled-content>s) with severe haemophilia A (<jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content>\u00a0\u2264\u00a00.01\u00a0IU\u00a0mL<jats:sup>\u22121<\/jats:sup>). All Canadian Haemophilia Treatment Centres completed a questionnaire on patients born between September 2005 and August 2010 and followed for up to 7\u00a0years. Eligible patients had at least 20 exposure days (<jats:styled-content style=\"fixed-case\">ED<\/jats:styled-content>) or had developed an inhibitor. The odds ratio (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>) and 95% confidence intervals (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>) for risk factors to develop an inhibitor were estimated using unconditional logistic regression. A total of 99 haemophilia A <jats:styled-content style=\"fixed-case\">PUP<\/jats:styled-content>s were studied. Thirty\u2010four (34%) developed an inhibitor (24\/34 of high titre). Inhibitors developed in 25\/63 (40%) patients with a high\u2010risk mutation. <jats:styled-content style=\"fixed-case\">ID<\/jats:styled-content> was most frequent in Aboriginals (86%). Dose intensity (<jats:styled-content style=\"fixed-case\">IU<\/jats:styled-content>\u00a0kg<jats:sup>\u22121<\/jats:sup>\u00a0day<jats:sup>\u22121<\/jats:sup> X number of <jats:styled-content style=\"fixed-case\">ED<\/jats:styled-content>) at first exposure to factor VIII (<jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content>) was associated with a crude <jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> increase of 1.10 (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 0.99\u20131.23) with each increase of 100 dose\u2010intensity units. Haemarthrosis and intracranial bleeding as the indication for first exposure to <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> concentrate were associated with a crude <jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> for <jats:styled-content style=\"fixed-case\">ID<\/jats:styled-content> of 7.63 (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 2.14\u201327.17) and 5.08 (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 1.11\u201323.31) respectively. <jats:styled-content style=\"fixed-case\">ID<\/jats:styled-content> according to <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> concentrate used was: Advate <jats:sup>\u00ae<\/jats:sup> 18\/50 (36%), Kogenate <jats:styled-content style=\"fixed-case\">FS<\/jats:styled-content><jats:sup>\u00ae<\/jats:sup> or Helixate <jats:styled-content style=\"fixed-case\">FS<\/jats:styled-content><jats:sup>\u00ae<\/jats:sup> 15\/36 (42%), Wilate<jats:sup>\u00ae<\/jats:sup> 0\/11 and Xyntha<jats:sup>\u00ae<\/jats:sup> 1\/2. In multivariate analysis, Aboriginal ethnicity (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>\u00a0=\u00a011.69; 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 1.11\u2013122.86) and haemarthrosis (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>\u00a0=\u00a04.49; 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 1.08\u201318.61) were statistically significant. The cumulative incidence of <jats:styled-content style=\"fixed-case\">ID<\/jats:styled-content> in severe haemophilia A <jats:styled-content style=\"fixed-case\">PUP<\/jats:styled-content>s was 34% and varied according to ethnicity, type of bleeding at first <jats:styled-content style=\"fixed-case\">ED<\/jats:styled-content>, type of <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> product and dose intensity at first exposure.<\/jats:p>","DOI":"10.1111\/hae.12479","type":"journal-article","created":{"date-parts":[[2014,7,17]],"date-time":"2014-07-17T14:06:27Z","timestamp":1405605987000},"page":"771-776","source":"Crossref","is-referenced-by-count":27,"title":["Incidence and risk factors for inhibitor development in previously untreated severe haemophilia A patients born between 2005 and 2010"],"prefix":"10.1111","volume":"20","author":[{"given":"C.","family":"V\u00e9zina","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology CHU Sainte\u2010Justine Montr\u00e9al Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Carcao","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology Research Institute Hospital for Sick Children University of Toronto Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Infante\u2010Rivard","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Biostatistics and Occupational Health Faculty of Medicine McGill University Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Lillicrap","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine Queen's University Kingston Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. M.","family":"Stain","sequence":"additional","affiliation":[{"name":"Department of Nursing Hospital for Sick Children Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Paradis","sequence":"additional","affiliation":[{"name":"Health Sciences North Sudbury Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Teitel","sequence":"additional","affiliation":[{"name":"Division of Hematology Oncology St\u2010Michael's Hospital Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. E.","family":"Rivard","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology CHU Sainte\u2010Justine Montr\u00e9al Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Association of Hemophilia Clinic Directors of Canada and of the Canadian Association of Nurses in Hemophilia Care","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,7,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.2003.00780.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-09-379453"},{"key":"e_1_2_9_4_1","first-page":"924","article-title":"Genetic defects and inhibitor development in siblings with severe hemophilia A","volume":"90","author":"Astermark J","year":"2005","journal-title":"Haematologica"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03636.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2001.02828.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-11-056291"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.03823.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2011.01.002"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2010.02231.x"},{"key":"e_1_2_9_11_1","unstructured":"Canadian Hemophilia Registry.Professor I. 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