Assessment of platelet activation and function in the early and late phases following acute TIA and ischaemic stroke

Abstract

Aims: The purpose of this thesis was to comprehensively assess the impact of commencing commonly prescribed antiplatelet regimens on platelet activation, platelet function and platelet turnover after TIA or ischaemic stroke, and to perform preliminary experiments to investigate coagulation system potential and endothelial activation in these patients. We also aimed to improve our understanding of the clinical and cellular mechanisms influencing non-responsiveness to antiplatelet therapy in the laboratory. Methods: A longitudinal observational study was performed to assess patients who changed from no medication to aspirin, aspirin to aspirin-dipyridamole combination therapy, or aspirin to clopidogrel ≤4 weeks of onset of a TIA or acute ischaemic stroke. Platelet activation and turnover were quantified with whole blood flow cytometry to assess the ‘unstimulated expression’ of platelet activation markers (CD62P and CD63), leucocyte-platelet complex formation and the percentage of circulating reticulated platelets. Inhibition of platelet function at moderately high shear stress was assessed with the platelet function analyser (PFA-100® collagen-ADP [C-ADP] and collagen- epinephrine [C-EPI] cartridges). A novel, ‘longitudinal definition’ of non-responsiveness on the PFA-100® was devised to overcome the limitations of ‘cross- sectional, case-control’ definitions of ex vivo antiplatelet non-responsiveness. Coagulation system potential was measured, and endothelial +/- platelet activation was quantified with von Willebrand factor and von Willebrand factor propeptide levels in platelet poor plasma in a subgroup of our patients.