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Relationship between ‘on-treatment platelet reactivity’, shear stress, and micro-embolic signals in asymptomatic and symptomatic carotid stenosis

  • S. J. X. Murphy
  • S. T. Lim
  • J. A. Kinsella
  • S. Tierney
  • B. Egan
  • T. M. Feeley
  • S. M. Murphy
  • R. A. Walsh
  • D. R. Collins
  • T. Coughlan
  • D. O’Neill
  • J. A. Harbison
  • P. Madhavan
  • S. M. O’Neill
  • M. P. Colgan
  • D. Cox
  • N. Moran
  • G. Hamilton
  • J. F. Meaney
  • D. J. H. McCabeEmail author
Original Communication

Abstract

Background

Assessment of ‘high on-treatment platelet reactivity (HTPR)’ could enhance understanding of the pathophysiology of first or recurrent vascular events in carotid stenosis patients on antiplatelet therapy.

Methods

This prospective, multi-centre study assessed antiplatelet–HTPR status and its relationship with micro-emboli signals (MES) in asymptomatic vs. symptomatic ≥ 50–99% carotid stenosis. Platelet function/reactivity was assessed under ‘moderately high shear stress’ with the PFA-100® and ‘low shear stress’ with VerifyNow® and Multiplate® analysers. Bilateral 1-h 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 TIA/ischaemic stroke. Median daily aspirin doses were higher in early symptomatic (225 mg; P < 0.001), but not late symptomatic (75 mg; P = 0.62) vs. asymptomatic patients (75 mg). There was a lower prevalence of aspirin–HTPR in early (28.6%; P = 0.028), but not late symptomatic (38.9%; P = 0.22) compared with asymptomatic patients (56.7%) on the PFA-100®, but not on the VerifyNow® or Multiplate® (P ≤ 0.53). Early symptomatic patients had a higher prevalence of aspirin–HTPR on the PFA-100® (28.6%) vs. VerifyNow® (9.5%; P = 0.049), but not Multiplate® assays (11.9%, P = 0.10). There was no difference in aspirin–HTPR prevalence between any symptomatic vs. asymptomatic MES + ve or MES − ve subgroup.

Discussion

Recently symptomatic moderate–severe carotid stenosis patients had a lower prevalence of aspirin–HTPR than their asymptomatic counterparts on the PFA-100®, likely related to higher aspirin doses. The prevalence of antiplatelet–HTPR was positively influenced by higher shear stress levels, but not MES status.

Keywords

Carotid stenosis Platelet function High on-treatment platelet reactivity Transcranial Doppler ultrasound Micro-embolic signals 

Notes

Acknowledgements

All HEIST collaborators qualified for authorship as they contributed to data acquisition or study design, and all critically appraised the 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, and by 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 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. All authors critically reviewed and approved the final submitted manuscript. The manuscript has not been submitted elsewhere and has not been published elsewhere in whole or in part, except as an abstract.

Compliance with ethical standards

Conflicts of interest

This study been approved by the local ethics committee and has, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons gave their written informed consent prior to their inclusion in the study. The authors declare that they have no conflicts of interest.

Supplementary material

415_2019_9550_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 14 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • S. J. X. Murphy
    • 2
    • 5
  • S. T. Lim
    • 2
    • 5
  • J. A. Kinsella
    • 7
  • S. Tierney
    • 3
  • B. Egan
    • 3
  • T. M. Feeley
    • 3
    • 6
  • S. M. Murphy
    • 2
    • 5
    • 16
  • R. A. Walsh
    • 2
    • 16
  • D. R. Collins
    • 4
    • 5
  • T. Coughlan
    • 4
    • 5
  • D. O’Neill
    • 4
    • 5
  • J. A. Harbison
    • 8
  • P. Madhavan
    • 9
  • S. M. O’Neill
    • 9
  • M. P. Colgan
    • 9
  • D. Cox
    • 10
    • 14
  • N. Moran
    • 10
    • 14
  • G. Hamilton
    • 11
  • J. F. Meaney
    • 12
  • D. J. H. McCabe
    • 1
    • 2
    • 5
    • 13
    • 14
    • 15
    • 16
    Email author
  1. 1.Vascular Neurology Research Foundation, C/O Department of NeurologyThe Adelaide and Meath Hospital, Dublin, Incorporating the National Children’s Hospital (AMNCH)/Tallaght University HospitalDublin 24Ireland
  2. 2.Department of NeurologyAMNCH/Tallaght University HospitalDublinIreland
  3. 3.Department of Vascular SurgeryAMNCH/Tallaght University HospitalDublinIreland
  4. 4.Age-Related Health Care DepartmentAMNCH/Tallaght University HospitalDublinIreland
  5. 5.Stroke ServiceAMNCH/Tallaght University HospitalDublinIreland
  6. 6.Dublin Midlands Hospital GroupDublinIreland
  7. 7.Department of Neurology, St Vincent’s University HospitalUniversity College DublinDublinIreland
  8. 8.Department of Medicine for the Elderly/Stroke ServiceSt. James’s Hospital/Trinity College DublinDublinIreland
  9. 9.Department of Vascular SurgerySt. James’s Hospital/Trinity College DublinDublinIreland
  10. 10.Department of Molecular and Cellular TherapeuticsRoyal College of Surgeons in IrelandDublinIreland
  11. 11.Department of Vascular Surgery, University Department of SurgeryRoyal Free Hampstead NHS TrustLondonUK
  12. 12.Department of Radiology, Centre for Advanced Medical ImagingSt. James’s Hospital/Trinity College DublinDublinIreland
  13. 13.Department of Clinical Neurosciences, Royal Free CampusUCL Queen Square Institute of NeurologyLondonUK
  14. 14.Irish Centre for Vascular BiologyDublinIreland
  15. 15.Stroke Clinical Trials Network IrelandDublinIreland
  16. 16.Academic Unit of Neurology, School of MedicineTrinity College DublinDublinIreland

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