{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T13:10:10Z","timestamp":1776085810860,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,7,24]],"date-time":"2015-07-24T00:00:00Z","timestamp":1437696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007658","name":"Baxter Healthcare Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007658","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008322","name":"CSL Behring","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:p><jats:bold>Introduction<\/jats:bold>: Von Willebrand disease (VWD) type 2N is characterized by a defective binding of factor VIII (FVIII) to von Willebrand factor (VWF) resulting in diminished plasma FVIII levels and a clinical phenotype mimicking mild haemophilia A. Several mutations in the FVIII binding site of VWF have been reported. <jats:bold>Aim:<\/jats:bold> This study aims to examine the effect of genotype on clinical phenotype in a cohort of VWD 2N patients. <jats:bold>Methods:<\/jats:bold> Patients with at least one genetically confirmed 2N mutation were selected retrospectively from a cohort of patients with suspected VWD. Clinical and laboratory phenotypes including bleeding scores (BS) were obtained and analysed. <jats:bold>Results<\/jats:bold>: Forty\u2010two VWD 2N patients with a mean age of 44\u00a0years were included. Eleven patients were homozygous or compound heterozygous (genetically confirmed group) and 31 patients were heterozygously affected (carriers group). Statistically significant differences between genetically confirmed VWD 2N patients and carriers were found in FVIII activity, VWF antigen levels, VWF\u2010FVIII binding capacity, FVIII\/VWF antigen ratio (all <jats:italic>P<\/jats:italic>&lt;0.001), VWF\u2010ristocetin activity (p=0.001) and VWF collagen binding (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.002). Median BS was 6 in genetically confirmed VWD 2N patients compared with 3 in carriers (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.047). Haemarthrosis, muscle haematomas and postpartum haemorrhage were only reported in genetically confirmed 2N patients. <jats:bold>Conclusion<\/jats:bold>: Phenotypic analysis showed that all laboratory parameters are lower in genetically confirmed VWD 2N patients compared with heterozygous 2N carriers. The clinical phenotype in genetically confirmed VWD 2N patients is comparable to mild haemophilia A patients and more severe than heterozygous 2N carriers.<\/jats:p>","DOI":"10.1111\/hae.12733","type":"journal-article","created":{"date-parts":[[2015,7,24]],"date-time":"2015-07-24T11:46:06Z","timestamp":1437738366000},"source":"Crossref","is-referenced-by-count":17,"title":["Clinical phenotype in genetically confirmed von Willebrand disease type 2N patients reflects a haemophilia A phenotype"],"prefix":"10.1111","volume":"21","author":[{"given":"M. E. R.","family":"van Meegeren","sequence":"first","affiliation":[{"name":"Hemophilia Treatment Center Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. L.","family":"Mancini","sequence":"additional","affiliation":[{"name":"Unit Thrombosis Hemostasis Laboratory of Hematology Department of Laboratory Medicine Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. C. M.","family":"Schoormans","sequence":"additional","affiliation":[{"name":"Unit Thrombosis Hemostasis Laboratory of Hematology Department of Laboratory Medicine Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. J. T.","family":"van Haren","sequence":"additional","affiliation":[{"name":"Unit Thrombosis Hemostasis Laboratory of Hematology Department of Laboratory Medicine Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"van Duren","sequence":"additional","affiliation":[{"name":"Unit Thrombosis Hemostasis Laboratory of Hematology Department of Laboratory Medicine Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Diekstra","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. A. P.","family":"Laros\u2010van Gorkom","sequence":"additional","affiliation":[{"name":"Hemophilia Treatment Center Radboud University Medical Center Nijmegen The Netherlands"},{"name":"Department of Hematology Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. P. T.","family":"Brons","sequence":"additional","affiliation":[{"name":"Hemophilia Treatment Center Radboud University Medical Center Nijmegen The Netherlands"},{"name":"Department of Pediatrics Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Simons","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Hoefsloot","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. L.","family":"van Heerde","sequence":"additional","affiliation":[{"name":"Hemophilia Treatment Center Radboud University Medical Center Nijmegen The Netherlands"},{"name":"Department of Pediatrics Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,7,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.67.1.395"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(87)80332-5"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V69.2.454.454"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1055\/s-0038-1648458","article-title":"Willebrand disease masquerading as haemophilia A","volume":"67","author":"Mazurier C","year":"1992","journal-title":"Thromb Haemost"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12380"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/beha.2001.0138"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03367.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V75.1.20.20"},{"key":"e_1_2_7_10_1","unstructured":"http:\/\/www.vwf.group.shef.ac.uk."},{"key":"e_1_2_7_11_1","unstructured":"http:\/\/www.ensembl.org."},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1651343"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2002.03488.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2257.2002.00480.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1309\/2D6F-RR03-8EFN-28F5"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2006.01847.x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH12-04-0244"},{"key":"e_1_2_7_18_1","first-page":"688","article-title":"Fainting induces an acute increase in the concentration of plasma factor VIII and von Willebrand factor","volume":"88","author":"Casonato A","year":"2003","journal-title":"Haematologica"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1613249"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1159\/000214852"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2004.05187.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2010.027177"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.215194"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/1076029606299000"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2011.02499.x"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2011.02617.x"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2008.03182.x"},{"key":"e_1_2_7_28_1","doi-asserted-by":"crossref","unstructured":"GillJC ChristophersonPA FloodVH FriedmanKD MontgomeryRR.Bleeding Scores in von Willebrand Disease (VWD) re\u2010visited: Analysis of the TS Zimmerman Program for the Molecular and Clinical Biology of VWD [abstract]. ASH Annual Meeting San Francisco CA.2008.","DOI":"10.1182\/blood.V112.11.425.425"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-02-557264"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhae.12733","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.12733","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T19:57:09Z","timestamp":1695499029000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.12733"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,24]]},"references-count":28,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,9]]}},"alternative-id":["10.1111\/hae.12733"],"URL":"https:\/\/doi.org\/10.1111\/hae.12733","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,24]]}}}