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Novel insights into the clinical phenotype and pathophysiology underlying low VWF levels

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dc.contributor.authorÁguila Martínez, Sonia
dc.contributor.authorLavin, Michelle
dc.contributor.authorSchneppenheim, Sonja
dc.contributor.authorDalton, Niall
dc.contributor.authorJones, Kenneth L.
dc.contributor.authorO’Sullivan, Jamie M.
dc.contributor.authorO’Connell, Niamh M.
dc.contributor.authorRyan, Kevin
dc.contributor.authorWhite, Barry
dc.contributor.authorByrne, Mary
dc.contributor.authorRafferty, Marie
dc.contributor.authorDoyle, Mairead M.
dc.contributor.authorNolan, Margaret
dc.contributor.authorPreston, Roger J. S.
dc.contributor.authorBudde, Ulrich
dc.contributor.authorJames, Paula
dc.contributor.authorDi Paola, Jorge
dc.contributor.authorO’Donnell, James S.
dc.contributor.departmentMedicina Interna
dc.date.accessioned2026-02-16T09:34:35Z
dc.date.available2026-02-16T09:34:35Z
dc.date.copyright© 2017 by The American Society of Hematology
dc.date.issued2017-11-23
dc.description.abstractCritical clinical questions remain unanswered regarding diagnosis and management of patients with low von Willebrand factor (VWF) levels (30-50 IU/dL). To address these questions, theLowVWFIreland Cohort (LoVIC) study investigated 126 patients registere with low VWF levels. Despite marginally reduced plasma VWF levels, International Society of Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH BAT) confirmed significant bleeding phenotypes in the majority of LoVIC patients. Importantly, bleeding tendency did not correlate with plasma VWF levels within the 30 to 50 IU/dL range. Furthermore, bleeding phenotypes could not be explained by concurrent hemostatic defects. Plasma factor VIII to VWF antigen (VWF:Ag) ratios were significantly increased in LoVIC patients compared with controls (P < .0001). In contrast, VWF propeptide to VWF:Ag ratios >3were observed in only 6%of the LoVICcohort. Furthermore, platelet-VWF collagen binding activity levels were both significantly reduced compared with controls (P < .05). In response to 1-desamino-8-D-arginine vasopressin (DDAVP), peak VWF:Ag levels exceeded 100IU/dLin 88%ofpatientsandwassustained >100 IU/dLafter 4 hours in72%of subjects. In conclusion, our novel data suggest that low VWF levels can be associated with significant bleeding and are predominantly due to reductions in VWF synthesis and/or constitutive secretion. Although enhanced VWF clearance may contribute to the pathophysiology in some individuals, the absolute reduction inVWF plasmahalf-lifeisusuallymildandnot sufficient tosignificantlyimpactuponthe durationofDDAVP-inducedVWFresponse. This trialwas registered at www.clinicaltrials.gov as #NCT03167320. (Blood. 2017;130(21):2344-2353)
dc.formatapplication/pdf
dc.format.extent10
dc.identifier.citationBlood 2017, Vol.130, nº21, 2344-2353
dc.identifier.doihttps://doi.org/10.1182/blood-2017-05-786699
dc.identifier.eissn1528-0020
dc.identifier.issn0006-4971
dc.identifier.urihttp://hdl.handle.net/10201/205481
dc.languageeng
dc.publisherAmerican Society of Hematology (ASH Publications)
dc.relationThis work was supported by an Irish Health Research Board Health Research Award (HRA-POR-2014-529) (J.S.O’D.) and a Science Foundation Ireland Principal Investigator Award (11/PI/1066) (J.S.O’D.)
dc.relation.publisherversionhttps://ashpublications.org/blood/article/130/21/2344/36657/Novel-insights-into-the-clinical-phenotype-and
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.odsObjetivo 3: Salud
dc.titleNovel insights into the clinical phenotype and pathophysiology underlying low VWF levels
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublicationes
relation.isAuthorOfPublication49779dfb-f4b4-4013-9b03-2ad7e3c247b7
relation.isAuthorOfPublication.latestForDiscovery49779dfb-f4b4-4013-9b03-2ad7e3c247b7
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