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Assessment of on-treatment platelet reactivity at high and low shear stress and platelet activation status after the addition of dipyridamole to aspirin in the early and late phases after TIA and ischaemic stroke

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posted on 2023-11-17, 14:44 authored by ST Lim, SJX Murphy, SM Murphy, T Coughlan, D O'Neill, Sean Tierney, B Egan, DR Collins, AJ McCarthy, SY Lim, DR Smith, Dermot CoxDermot Cox, DJH McCabe

Background: Data are limited on the ability of dipyridamole to additionally inhibit platelet function/reactivity in ischaemic cerebrovascular disease (CVD) patients on aspirin.

Aims: To assess inhibition of platelet function/reactivity and platelet activation with dipyridamole in CVD.

Methods: This prospective, observational study assessed TIA/ischaemic stroke patients before (baseline; N = 60), at 14 ±7 days (14d, N = 39) and ≥ 90 days (90d, N = 31) after adding dipyridamole to aspirin. Platelet function/reactivity at high shear stress (PFA-100® C-ADP) and low shear stress (VerifyNow® P2Y12 and Multiplate® ADP assays), and platelet activation status (% expression of CD62P, CD63 and leucocyte-platelet complexes on whole blood flow cytometry) were quantified. 'Dipyridamole-high on-treatment platelet reactivity (HTPR)' was defined as failure to inhibit ADP-induced platelet aggregation +/- adhesion compared with the patient's baseline on aspirin monotherapy by more than twice the coefficient-of-variation of the assay after adding dipyridamole to aspirin.

Results: Dipyridamole-HTPR was identified in 71.4-75% of patients on PFA-100 C-ADP, 83.9-86.8% of patients on VerifyNow P2Y12, and 81.5-83.3% of patients on Multiplate ADP assays. There were no changes in CD62P/CD63 expression (P ≥ 0.18), or consistent changes in leucocyte-platelet complexes in CVD patients overall at 14d or 90d vs. baseline after commencing dipyridamole. Monocyte-platelet complexes increased in the patient subgroup with dipyridamole-HTPR at 14d and 90d on PFA-100, and at 14d on VerifyNow (P ≤ 0.04), but not in those without dipyridamole-HTPR.

Discussion: Additional antiplatelet effects of dipyridamole are detectable under high and low shear stress conditions with user-friendly platelet function/reactivity tests ex vivo. Increasing circulating monocyte-platelet complexes over time are associated with dipyridamole-HTPR.

Funding

The Meath Foundation

The Irish Institute of Clinical Neuroscience/Novartis Ireland Fellowship Grant

The Vascular Neurology Research Foundation Ireland

Irish Heart Foundation Stroke Prevention Bursary programme

Biogen Idec, Ireland

Verum Diagnostica, GmbH

Trinity College Dublin Innovation Bursary

Joint Irish Institute of Clinical Neuroscience/Merck Serono Fellowship in Neuroscience Grant

Bayer HealthCare, Ireland

History

Comments

The original article is available at https://www.jns-journal.com/

Published Citation

Lim ST. et al. Assessment of on-treatment platelet reactivity at high and low shear stress and platelet activation status after the addition of dipyridamole to aspirin in the early and late phases after TIA and ischaemic stroke. J Neurol Sci. 2022 ;441:120334

Publication Date

11 July 2022

PubMed ID

36030623

Department/Unit

  • Irish Centre for Vascular Biology
  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Health Professions Education
  • Surgical Science and Practice
  • Immunity, Infection and Inflammation
  • Vascular Biology

Publisher

Elsevier

Version

  • Published Version (Version of Record)