{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T13:41:43Z","timestamp":1778938903049,"version":"3.51.4"},"reference-count":0,"publisher":"Georg Thieme Verlag KG","issue":"03","funder":[{"name":"Baxalta US Inc.","award":["H13\u2013000845"],"award-info":[{"award-number":["H13\u2013000845"]}]},{"name":"Spanish Ministry of the Economy and Competitiveness"},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","award":["PI15\/01643"],"award-info":[{"award-number":["PI15\/01643"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The clinical diagnosis of von Willebrand disease (VWD), particularly type 1, can be complex because several genetic and environmental factors affect von Willebrand factor (VWF) plasma levels. An estimated 60% of the phenotypic variation is attributable to hereditary factors, with the ABO blood group locus being the most influential. However, recent studies provide strong evidence that nonsynonymous single nucleotide variants (SNVs) contribute to VWF and factor VIII phenotypic variability in healthy individuals. This study aims to investigate the role of common VWF SNVs on VWD phenotype by analyzing data from 219 unrelated patients included in the \u201cMolecular and Clinical Profile of von Willebrand Disease in Spain project.\u201d To that end, generalized linear mixed-effects regression models were fitted, and additive and epistatic analyses, and haplotype studies were performed, considering five VWD-related measures (bleeding score, VWF:Ag, VWF:RCo, factor VIII:C, and VWF:CB). According to these analyses, homozygotes: for p.Thr789Ala(C) would be expected to show 39% higher VWF:Ag levels; p.Thr1381Ala(C), 27% lower VWF:Ag levels; and p.Gln852Arg(C), 52% lower VWF:RCo levels. Homozygotes for both p.Thr789Ala(C) and p.Gln852Arg(T) were predicted to show 185% higher VWF:CB activity, and carriers of two copies of the p.Thr1381Ala(T)\/p.Gln852Arg(T) haplotype would present a 100% increase in VWF:RCo activity. These results indicate a substantial effect of common VWF variation on VWD phenotype. Although additional studies are needed to determine the true magnitude of the effects of SNVs on VWF, these findings provide new evidence regarding the contribution of common variants to VWD, which should be taken into account to enhance the accuracy of the diagnosis and classification of this condition. ClinicalTrials.gov identifier: NCT02869074.<\/jats:p>","DOI":"10.1055\/s-0040-1702227","type":"journal-article","created":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T23:37:27Z","timestamp":1583451447000},"page":"437-448","source":"Crossref","is-referenced-by-count":6,"title":["Unraveling the Influence of Common von Willebrand factor variants on von Willebrand Disease Phenotype: An Exploratory Study on the Molecular and Clinical Profile of von Willebrand Disease in Spain Cohort"],"prefix":"10.1055","volume":"120","author":[{"given":"Nina","family":"Borr\u00e0s","sequence":"additional","affiliation":[{"name":"Congenital Coagulopathies, Banc de Sang i Teixits, Barcelona, Spain"},{"name":"Transfusional Medicine, Vall d\u2019Hebron Research Institute, Universitat Aut\u00f2noma de Barcelona (VHIR-UAB), Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iris","family":"Garcia-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Congenital Coagulopathies, Banc de Sang i Teixits, Barcelona, Spain"},{"name":"Transfusional Medicine, Vall d\u2019Hebron Research Institute, Universitat Aut\u00f2noma de Barcelona (VHIR-UAB), Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Batlle","sequence":"additional","affiliation":[{"name":"Department of Hematology, Complexo Hospitalario Universitario A Coru\u00f1a, INIBIC, A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Almudena","family":"P\u00e9rez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Department of Hematology, Complexo Hospitalario Universitario A Coru\u00f1a, INIBIC, A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Parra","sequence":"additional","affiliation":[{"name":"Congenital Coagulopathies, Banc de Sang i Teixits, Barcelona, Spain"},{"name":"Transfusional Medicine, Vall d\u2019Hebron Research Institute, Universitat Aut\u00f2noma de Barcelona (VHIR-UAB), Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carme","family":"Altisent","sequence":"additional","affiliation":[{"name":"Transfusional Medicine, Vall d\u2019Hebron Research Institute, Universitat Aut\u00f2noma de Barcelona (VHIR-UAB), Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Fernanda","family":"L\u00f3pez-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Hematology, Complexo Hospitalario Universitario A Coru\u00f1a, INIBIC, A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joana","family":"Costa Pinto","sequence":"additional","affiliation":[{"name":"Department of Hematology, Complexo Hospitalario Universitario A Coru\u00f1a, INIBIC, A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Batlle-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Research, Lapisoft SA, A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Rosa","family":"Cid","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario y Polit\u00e9cnico La Fe, Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santiago","family":"Bonanad","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario y Polit\u00e9cnico La Fe, Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noelia","family":"Cabrera","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario y Polit\u00e9cnico La Fe, Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9s","family":"Moret","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario y Polit\u00e9cnico La Fe, Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Eva","family":"Mingot-Castellano","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Regional Universitario de M\u00e1laga, M\u00e1laga, Spain"},{"name":"Hospital Universitario Virgen del Rocio, Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nira","family":"Navarro","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario Dr. Negr\u00edn, Las Palmas de Gran Canaria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roc\u00edo","family":"P\u00e9rez-Montes","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario Marqu\u00e9s de Valdecilla, Santander, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shally","family":"Marcellini","sequence":"additional","affiliation":[{"name":"Department of Hematology, Salud Castilla y Le\u00f3n, Segovia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Moreto","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario Cruces, Barakaldo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Herrero","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario de Guadalajara, Guadalajara, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inmaculada","family":"Soto","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario Central de Asturias, Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N\u00faria","family":"Fern\u00e1ndez-Mosteir\u00edn","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario Miguel Servet, Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V\u00edctor","family":"Jim\u00e9nez-Yuste","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario La Paz, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nieves","family":"Alonso","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Infanta Cristina, Badajoz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aurora","family":"de Andr\u00e9s-Jacob","sequence":"additional","affiliation":[{"name":"Department of Hematology, Complexo Hospitalario Universitario Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilia","family":"Fontanes","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario Lucus Augusti, Lugo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Campos","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Jerez de la Frontera, C\u00e1diz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Paloma","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Virgen del Camino, Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuria","family":"Bermejo","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital San Pedro de Alc\u00e1ntara, C\u00e1ceres, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rub\u00e9n","family":"Berrueco","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Sant Joan de Deu, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Mateo","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Sta Creu i St Pau, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karmele","family":"Arribalzaga","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario Fundaci\u00f3n Alcorc\u00f3n, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascual","family":"Marco","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital General de Alicante, Alicante, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1ngeles","family":"Palomo","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Regional Universitario de M\u00e1laga, M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nerea","family":"Castro Quismondo","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario 12 de Octubre, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bel\u00e9n","family":"I\u00f1igo","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Cl\u00ednico San Carlos, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"del Mar Nieto","sequence":"additional","affiliation":[{"name":"Department of Hematology, Complejo Hospitalario de Ja\u00e9n, Ja\u00e9n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Vidal","sequence":"additional","affiliation":[{"name":"Department of Hematology, Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Paz","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Nuestra Sra. de Sonsoles, \u00c1vila, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reyes","family":"Aguinaco","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Joan XXIII, Tarragona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Tenorio","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Ram\u00f3n y Cajal, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Ferreiro","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Montecelo, Pontevedra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Garc\u00eda-Frade","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital R\u00edo Hortega, Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Mar\u00eda","family":"Rodr\u00edguez-Huerta","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Gregorio Mara\u00f1\u00f3n, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Cuesta","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Virgen de la Salud, Toledo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ram\u00f3n","family":"Rodr\u00edguez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Severo Ochoa, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faustino","family":"Garc\u00eda-Candel","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario Virgen Arrixaca, Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Dob\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Lozano Blesa, Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Santa B\u00e1rbara, Soria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Corrales","sequence":"additional","affiliation":[{"name":"Congenital Coagulopathies, Banc de Sang i Teixits, Barcelona, Spain"},{"name":"Transfusional Medicine, Vall d\u2019Hebron Research Institute, Universitat Aut\u00f2noma de Barcelona (VHIR-UAB), Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Vidal","sequence":"additional","affiliation":[{"name":"Congenital Coagulopathies, Banc de Sang i Teixits, Barcelona, Spain"},{"name":"Transfusional Medicine, Vall d\u2019Hebron Research Institute, Universitat Aut\u00f2noma de Barcelona (VHIR-UAB), Barcelona, Spain"},{"name":"CIBER de Enfermedades Cardiovasculares (CIBERCV), Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2020,3,5]]},"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0040-1702227.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T23:37:51Z","timestamp":1583451471000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0040-1702227"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3]]},"references-count":0,"journal-issue":{"issue":"03","published-online":{"date-parts":[[2020,3,5]]},"published-print":{"date-parts":[[2020,3]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0040-1702227","relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3]]}}}