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Thromb Haemost 2021; 121(01): 086-097
DOI: 10.1055/s-0040-1715440
Stroke, Systemic or Venous Thromboembolism

von Willebrand Factor Antigen, von Willebrand Factor Propeptide, and ADAMTS13 in Carotid Stenosis and Their Relationship with Cerebral Microemboli

Stephen J. X. Murphy 
1   Department of Neurology, The Adelaide and Meath Hospital, Dublin incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
2   Stroke Service, AMNCH/Tallaght University Hospital, Dublin, Ireland
,
Soon Tjin Lim 
1   Department of Neurology, The Adelaide and Meath Hospital, Dublin incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
2   Stroke Service, AMNCH/Tallaght University Hospital, Dublin, Ireland
3   Department of Clinical Neurosciences, Royal Free Campus, UCL Queen Square Institute of Neurology, London, United Kingdom
,
Fionnuala Hickey
4   Department of Clinical Medicine, Trinity Centre for Health Sciences, School of Medicine, Trinity College, Dublin, Ireland
,
Justin A. Kinsella
5   Department of Neurology, St Vincent’s University Hospital and University College Dublin, Dublin, Ireland
,
Deirdre R. Smith
1   Department of Neurology, The Adelaide and Meath Hospital, Dublin incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
6   Vascular Neurology Research Foundation, C/O Dept of Neurology, AMNCH/Tallaght University Hospital, Dublin, Ireland
,
Sean Tierney
7   Department of Vascular Surgery, AMNCH/Tallaght University Hospital, Dublin, Ireland
,
Bridget Egan
7   Department of Vascular Surgery, AMNCH/Tallaght University Hospital, Dublin, Ireland
,
T. Martin Feeley
7   Department of Vascular Surgery, AMNCH/Tallaght University Hospital, Dublin, Ireland
8   Clinical Directorate, Dublin Midlands Hospital Group, Dublin Ireland
,
Sinéad M. Murphy
1   Department of Neurology, The Adelaide and Meath Hospital, Dublin incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
2   Stroke Service, AMNCH/Tallaght University Hospital, Dublin, Ireland
9   Academic Unit of Neurology, School of Medicine, Trinity College Dublin, Dublin, Ireland
,
D. Rónán Collins
2   Stroke Service, AMNCH/Tallaght University Hospital, Dublin, Ireland
10   Age-Related Health Care Department, AMNCH/Tallaght University Hospital, Dublin, Ireland
,
Tara Coughlan
2   Stroke Service, AMNCH/Tallaght University Hospital, Dublin, Ireland
10   Age-Related Health Care Department, AMNCH/Tallaght University Hospital, Dublin, Ireland
,
Desmond O'Neill
2   Stroke Service, AMNCH/Tallaght University Hospital, Dublin, Ireland
10   Age-Related Health Care Department, AMNCH/Tallaght University Hospital, Dublin, Ireland
,
Joseph A. Harbison
11   Department of Medicine for the Elderly/Stroke Service, St James's Hospital and School of Medicine, Trinity College Dublin, Dublin, Ireland
,
Prakash Madhavan
12   Department of Vascular Surgery, St James's Hospital, Dublin, Ireland
,
Sean M. O'Neill
12   Department of Vascular Surgery, St James's Hospital, Dublin, Ireland
,
Mary-Paula Colgan
12   Department of Vascular Surgery, St James's Hospital, Dublin, Ireland
,
James S. O'Donnell
13   Department of Haematology, St James's Hospital, Dublin, Ireland
14   Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland
15   Irish Centre for Vascular Biology, Royal College of Surgeons in Ireland, Dublin, Ireland
,
Jamie M. O'Sullivan
14   Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland
15   Irish Centre for Vascular Biology, Royal College of Surgeons in Ireland, Dublin, Ireland
,
George Hamilton
16   Department of Vascular Surgery, University Department of Surgery, Royal Free Hampstead NHS Trust, London, United Kingdom
,
Dominick J. H. McCabe 
1   Department of Neurology, The Adelaide and Meath Hospital, Dublin incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
2   Stroke Service, AMNCH/Tallaght University Hospital, Dublin, Ireland
3   Department of Clinical Neurosciences, Royal Free Campus, UCL Queen Square Institute of Neurology, London, United Kingdom
6   Vascular Neurology Research Foundation, C/O Dept of Neurology, AMNCH/Tallaght University Hospital, Dublin, Ireland
9   Academic Unit of Neurology, School of Medicine, Trinity College Dublin, Dublin, Ireland
15   Irish Centre for Vascular Biology, Royal College of Surgeons in Ireland, Dublin, Ireland
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Abstract

Background The relationship between von Willebrand factor antigen (VWF:Ag), VWF propeptide (VWFpp), VWFpp/VWF:Ag ratio, ADAMTS13 activity, and microembolic signal (MES) status in carotid stenosis is unknown.

Methods This prospective, multicenter study simultaneously assessed plasma VWF:Ag levels, VWFpp levels and ADAMTS13 activity, and their relationship with MES in asymptomatic versus symptomatic moderate-to-severe (≥50–99%) carotid stenosis patients. One-hour transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES+ve or MES−ve.

Results Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the “early phase” (≤4 weeks) and 37 patients in the “late phase” (≥3 months) after transient ischemic attack (TIA)/ischemic stroke. VWF:Ag levels were higher (p = 0.049) and VWFpp/VWF:Ag ratios lower (p = 0.006) in early symptomatic than in asymptomatic patients overall, and in early symptomatic versus asymptomatic MES−ve subgroups (p ≤0.02). There were no intergroup differences in VWFpp expression or ADAMTS13 activity (p ≥0.05). VWF:Ag levels and ADAMTS13 activity decreased (p ≤ 0.048) and VWFpp/VWF:Ag ratios increased (p = 0.03) in symptomatic patients followed up from the early to late phases after TIA/stroke. Although there were no differences in the proportions of symptomatic and asymptomatic patients with blood group O, a combined analysis of early symptomatic and asymptomatic patients revealed lower median VWF:Ag levels in patients with blood group O versus those without blood group O (9.59 vs. 12.32 µg/mL, p = 0.035).

Discussion VWF:Ag expression, a marker of endothelial ± platelet activation, is enhanced in recently symptomatic versus asymptomatic carotid stenosis patients, including in MES−ve patients, and decreases with ADAMTS13 activity over time following atherosclerotic TIA/ischemic stroke.

Keywords

carotid stenosis - von Willebrand factor antigen - von Willebrand factor propeptide - ADAMTS13 activity - transcranial Doppler ultrasound

Note

All HEIST collaborators qualified for authorship because they contributed to data acquisition or study design, and all critically appraised and approved the final submitted manuscript for important intellectual content. Dr Murphy's research was funded by the Trinity College Dublin Innovation Bursary, the Meath Foundation, Ireland, Joint IICN/Merck Serono Fellowship in Neuroscience, the Vascular Neurology Research Foundation, Ireland, an unrestricted educational grant from Bayer HealthCare Ireland, and Verum Diagnostica, GmbH. Dr. Lim's research was funded by the Meath Foundation, Ireland, the Irish Institute of Clinical Neuroscience (IICN)/Novartis Ireland Fellowship Grant, the Vascular Neurology Research Foundation, Ireland, the Irish Heart Foundation Stroke Prevention Bursary, and by unrestricted educational grant funding from Biogen Idec Ireland. None of the above charities or funding bodies had any influence on design or conduct of this study, or had any influence on the decision to submit the final manuscript for publication. The manuscript has not been submitted elsewhere and has not been published elsewhere in whole or in part, except as an abstract.




Publication History

Received: 07 December 2019

Accepted: 26 June 2020

Article published online:
15 September 2020

© 2021. Thieme. All rights reserved.

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