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Open Access
CC BY 4.0 · TH Open 2023; 07(04): e294-e302
DOI: 10.1055/s-0043-1776328
Original Article

Platelet Receptor Glycoprotein VI-Dimer Is Overexpressed in Patients with Atrial Fibrillation at High Risk of Ischemic Stroke

Authors

  • Isuru Induruwa 

    1   Department of Clinical Neurosciences, University of Cambridge, Cambridgeshire, United Kingdom of Great Britain and Northern Ireland

  • Carly Kempster 

    2   Department of Haematology, University of Cambridge, Cambridgeshire, United Kingdom of Great Britain and Northern Ireland

  • Patrick Thomas

    2   Department of Haematology, University of Cambridge, Cambridgeshire, United Kingdom of Great Britain and Northern Ireland

  • Harriet McKinney

    2   Department of Haematology, University of Cambridge, Cambridgeshire, United Kingdom of Great Britain and Northern Ireland

  • Jean-Daniel Malcor

    3   Department of Biochemistry, University of Cambridge, Cambridgeshire, United Kingdom of Great Britain and Northern Ireland

  • Arkadiusz Bonna

    3   Department of Biochemistry, University of Cambridge, Cambridgeshire, United Kingdom of Great Britain and Northern Ireland

  • Joana Batista

    2   Department of Haematology, University of Cambridge, Cambridgeshire, United Kingdom of Great Britain and Northern Ireland

  • Kenji Soejima

    4   Research and Development Coordination and Administration Department, KM Biologics Co., Ltd., Cambridgeshire, United Kingdom of Great Britain and Northern Ireland

  • Willem Ouwehand

    2   Department of Haematology, University of Cambridge, Cambridgeshire, United Kingdom of Great Britain and Northern Ireland

  • Richard W. Farndale 

    3   Department of Biochemistry, University of Cambridge, Cambridgeshire, United Kingdom of Great Britain and Northern Ireland

  • Kate Downes

    2   Department of Haematology, University of Cambridge, Cambridgeshire, United Kingdom of Great Britain and Northern Ireland

  • Masaaki Moroi

    3   Department of Biochemistry, University of Cambridge, Cambridgeshire, United Kingdom of Great Britain and Northern Ireland

  • Stephanie M. Jung

    3   Department of Biochemistry, University of Cambridge, Cambridgeshire, United Kingdom of Great Britain and Northern Ireland

  • Elizabeth A. Warburton

    1   Department of Clinical Neurosciences, University of Cambridge, Cambridgeshire, United Kingdom of Great Britain and Northern Ireland

Funding This study was funded by a Special Project Grant from the British Heart Foundation (SP/13/7/30575 to S.M.J., R.W.F., ad E.A.W.). I.I.'s work is supported by the UK NIHR (National Institute for Health Research), a British Heart Foundation Cambridge Centre for Cardiovascular Research Excellence Clinical Training Fellowship (RE/13/6/30180), and an Addenbrooke's Charitable Trust Grant. K.D. is a Higher Specialist Scientist Trainee supported by NHS Health Education England. E.A.W. is supported by the UK NIHR.
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Graphical Abstract

Abstract

Introduction Atrial fibrillation (AF) increases the risk of ischemic stroke (IS). We hypothesized that the functional form of platelet receptor glycoprotein (GP) VI, GPVI-dimer, which binds to collagen and fibrin causing platelet activation, is overexpressed in patients with AF who have not had a stroke.

Methods A total of 75 inpatients with AF were recruited. None were admitted with or had previously had thrombotic events, including IS or myocardial infarction. Platelet surface expression of total GPVI, GPVI-dimer, and the platelet activation marker P-selectin were quantitated by whole blood flow cytometry. Serum biomarkers were collected in AF patients. Results were compared against patients contemporaneously admitted to hospital with similar age and vascular risk-factor profiles without AF (noAF, n = 30).

Results Patients with AF have similar total GPVI surface expression (p = 0.58) and P-selectin exposure (p = 0.73) on their platelets compared with noAF patients but demonstrate significantly higher GPVI-dimer expression (p = 0.02). Patients with paroxysmal AF express similar GPVI-dimer levels compared with permanent AF and GPVI-dimer levels were not different between anticoagulated groups. Serum N-terminal pro b-type natriuretic peptide (p < 0.0001) and high sensitivity C-reactive protein (p < 0.0001) were significantly correlated with GPVI-dimer expression in AF platelets. AF was the only vascular risk factor that was independently associated with higher GPVI-dimer expression in the whole population (p = 0.02).

Conclusion GPVI inhibition is being explored in clinical trials as a novel target for IS treatment. As GPVI-dimer is elevated in AF patients' platelets, the exploration of targeted GPVI-dimer inhibition for stroke prevention in patients at high risk of IS due to AF is supported.

Keywords

atrial fibrillation - platelets - thrombosis - ischemic stroke

Supplementary Material



Publication History

Received: 13 June 2023

Accepted: 31 August 2023

Article published online:
13 November 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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