Pilot study of on-treatment platelet reactivity at low shear stress and platelet activation status on aspirin or clopidogrel monotherapy in patients with TIA or ischaemic stroke

S T Lim; S J X Murphy; D R Smith; D R Collins; T Coughlan; S M Murphy; A J McCarthy; B Egan; S-Y Lim; D Cox; D J H McCabe

doi:10.1016/j.jns.2025.123540

Pilot study of on-treatment platelet reactivity at low shear stress and platelet activation status on aspirin or clopidogrel monotherapy in patients with TIA or ischaemic stroke

J Neurol Sci. 2025 May 17:475:123540. doi: 10.1016/j.jns.2025.123540. Online ahead of print.

Authors

S T Lim¹, S J X Murphy², D R Smith³, D R Collins⁴, T Coughlan⁴, S M Murphy⁵, A J McCarthy², B Egan⁶, S-Y Lim⁷, D Cox⁸, D J H McCabe⁹

Affiliations

¹ Department of Neurology, Tallaght University Hospital/The Adelaide and Meath Hospital, Dublin, Incorporating the National Children's Hospital (AMNCH), Dublin, Ireland; Stroke Service, Tallaght University Hospital/The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH), Dublin, Ireland; Dept. of Clinical and Movement Neurosciences, Royal Free Campus, UCL Queen Square Institute of Neurology, London, UK; Dept. of Clinical Neurophysiology, Kings College Hospital NHS Trust, London, UK.
² Department of Neurology, Tallaght University Hospital/The Adelaide and Meath Hospital, Dublin, Incorporating the National Children's Hospital (AMNCH), Dublin, Ireland; Stroke Service, Tallaght University Hospital/The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH), Dublin, Ireland; Academic Unit of Neurology, School of Medicine, Trinity College Dublin, Ireland.
³ Department of Neurology, Tallaght University Hospital/The Adelaide and Meath Hospital, Dublin, Incorporating the National Children's Hospital (AMNCH), Dublin, Ireland; Vascular Neurology Research Foundation, Tallaght University Hospital/The Adelaide and Meath Hospital, Dublin, Incorporating the National Children's Hospital (AMNCH), Dublin, Ireland; Academic Unit of Neurology, School of Medicine, Trinity College Dublin, Ireland.
⁴ Stroke Service, Tallaght University Hospital/The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH), Dublin, Ireland; Age-Related Health Care Department, Tallaght University Hospital/The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH), Dublin, Ireland.
⁵ Department of Neurology, Tallaght University Hospital/The Adelaide and Meath Hospital, Dublin, Incorporating the National Children's Hospital (AMNCH), Dublin, Ireland; Academic Unit of Neurology, School of Medicine, Trinity College Dublin, Ireland.
⁶ Department of Vascular Surgery, Tallaght University Hospital/The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH), Dublin, Ireland.
⁷ Faculty of Health and Medical Sciences, Taylor's University, Malaysia.
⁸ School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland; Irish Centre for Vascular Biology, Dublin, Ireland.
⁹ Department of Neurology, Tallaght University Hospital/The Adelaide and Meath Hospital, Dublin, Incorporating the National Children's Hospital (AMNCH), Dublin, Ireland; Vascular Neurology Research Foundation, Tallaght University Hospital/The Adelaide and Meath Hospital, Dublin, Incorporating the National Children's Hospital (AMNCH), Dublin, Ireland; Stroke Service, Tallaght University Hospital/The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH), Dublin, Ireland; Dept. of Clinical and Movement Neurosciences, Royal Free Campus, UCL Queen Square Institute of Neurology, London, UK; Irish Centre for Vascular Biology, Dublin, Ireland; Stroke Clinical Trials Network Ireland, Dublin, Ireland; Academic Unit of Neurology, School of Medicine, Trinity College Dublin, Ireland. Electronic address: dominick.mccabe@tuh.ie.

PMID: 40554175
DOI: 10.1016/j.jns.2025.123540

Abstract

Background: Simultaneously-collected data regarding platelet reactivity and activation in ischaemic cerebrovascular disease (CVD) patients starting antiplatelet agents are limited.

Methods: This prospective observational pilot study assessed platelet reactivity and activation in TIA/ischaemic stroke patients before (baseline; N = 73), 14 ± 7 days (14d; N = 59) and ≥ 90 days (90d; N = 38) after commencing aspirin or clopidogrel monotherapy. Platelet reactivity at low shear-stress (Multiplate® Aspirin/ADP assays) and platelet activation status (% expression of CD62P, CD63, and leucocyte-platelet complexes by flow cytometry) were quantified in whole blood. Prevalence of high on-treatment platelet reactivity (HTPR) was determined on Multiplate with 'case-control definitions' (Aspirin-HTPR:>40 U; Clopidogrel-HTPR:>46 U), and innovative 'longitudinal-HTPR definitions' (failure to reduce aggregation compared with the patient's baseline by more than twice the co-efficient of variation of the relevant assay).

Results: Prevalence of case-control aspirin-HTPR was 23.8 % at 14d and 30.8 % at 90d, and of longitudinal aspirin-HTPR was 4.8 % at 14d and 0 % at 90d. Prevalence of clopidogrel-HTPR was significantly higher with case-control than longitudinal definitions at 14d (60.5 % vs. 21 %) and 90d (52 % vs. 24 %) (P ≤ 0.03). % Neutrophil-platelet complexes (P = 0.04) and lymphocyte-platelet complexes (P = 0.002) were higher in patients with vs. without case-control clopidogrel-HTPR at 14d. Median % lymphocyte-platelet complexes significantly decreased between baseline and 14d (P = 0.019), and monocyte-platelet complexes decreased between baseline and 90d (P = 0.017) only in the clopidogrel-patient subgroup whose platelets were adequately inhibited by clopidogrel.

Conclusions: Antiplatelet-HTPR prevalence is higher in CVD patients with case-control than longitudinal definitions on the Multiplate analyser. Quantifying leucocyte-platelet complexes improves our understanding of cellular mechanisms contributing to case-control clopidogrel-HTPR.

Keywords: Antiplatelet therapy; Flow cytometry; High on-treatment platelet reactivity (HTPR); Ischaemic stroke; Multiplate® analyser; Platelet function/reactivity; Transient ischaemic attack.