TY - JOUR
T1 - Novel insights into the clinical phenotype and pathophysiology underlying low VWF levels
AU - Lavin, Michelle
AU - Aguila, Sonia
AU - Schneppenheim, Sonja
AU - Dalton, Niall
AU - Jones, Kenneth L.
AU - O’Sullivan, Jamie M.
AU - O’Connell, Niamh M.
AU - Ryan, Kevin
AU - White, Barry
AU - Byrne, Mary
AU - Rafferty, Marie
AU - Doyle, Mairead M.
AU - Nolan, Margaret
AU - Preston, Roger J.S.
AU - Budde, Ulrich
AU - James, Paula
AU - Di Paola, Jorge
AU - O’Donnell, James S.
N1 - Publisher Copyright:
© 2017 by The American Society of Hematology.
PY - 2017/11/23
Y1 - 2017/11/23
N2 - 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, the Low VWF Ireland Cohort (LoVIC) study investigated 126 patients registered 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 >3 were observed in only 6% of the LoVIC cohort. 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 100 IU/dL in 88% of patients and was sustained >100 IU/dL after 4 hours in 72% of subjects. In conclusion, our novel data suggest that low VWF levels can be associated with significant bleedin and are predominantl due to reductions in VWF s nthesis and/or constitutive secretion. Although enhanced VWF clearance may contribute to the pathophysiology in some individuals, the absolute reduction in VWF plasma half-life is usually mild and not sufficient to significantly impact upon the duration of DDAVP-induced VWF response. This trial was registered at www.clinicaltrials.gov as #NCT03167320.
AB - 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, the Low VWF Ireland Cohort (LoVIC) study investigated 126 patients registered 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 >3 were observed in only 6% of the LoVIC cohort. 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 100 IU/dL in 88% of patients and was sustained >100 IU/dL after 4 hours in 72% of subjects. In conclusion, our novel data suggest that low VWF levels can be associated with significant bleedin and are predominantl due to reductions in VWF s nthesis and/or constitutive secretion. Although enhanced VWF clearance may contribute to the pathophysiology in some individuals, the absolute reduction in VWF plasma half-life is usually mild and not sufficient to significantly impact upon the duration of DDAVP-induced VWF response. This trial was registered at www.clinicaltrials.gov as #NCT03167320.
UR - http://www.scopus.com/inward/record.url?scp=85034847206&partnerID=8YFLogxK
U2 - 10.1182/blood-2017-05-786699
DO - 10.1182/blood-2017-05-786699
M3 - Article
C2 - 28916584
AN - SCOPUS:85034847206
SN - 0006-4971
VL - 130
SP - 2344
EP - 2353
JO - Blood
JF - Blood
IS - 21
ER -