Publication: Novel insights into the clinical phenotype and pathophysiology underlying low VWF levels
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Date
2017-11-23
Authors
Águila Martínez, Sonia ; Lavin, Michelle ; Schneppenheim, Sonja ; Dalton, Niall ; Jones, Kenneth L. ; O’Sullivan, Jamie M. ; O’Connell, Niamh M. ; Ryan, Kevin ; White, Barry ; Byrne, Mary ; Rafferty, Marie ; Doyle, Mairead M. ; Nolan, Margaret ; Preston, Roger J. S. ; Budde, Ulrich ; James, Paula ; Di Paola, Jorge ; O’Donnell, James S.
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Publisher
American Society of Hematology (ASH Publications)
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DOI
https://doi.org/10.1182/blood-2017-05-786699
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info:eu-repo/semantics/article
Description
Abstract
Critical 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)
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Citation
Blood 2017, Vol.130, nº21, 2344-2353
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