Longitudinal assessment of thrombin generation potential in response to alteration of antiplatelet therapy after TIA or ischaemic stroke
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The impact of changing antiplatelet therapy on thrombin generation potential in patients with ischaemic cerebrovascular disease (CVD) is unclear. We assessed patients within 4 weeks of TIA or ischaemic stroke (baseline), and then 14 days (14d) and >90 days (90d) after altering antiplatelet therapy. Thrombin generation was assessed in platelet poor plasma. Ninety-one patients were recruited. Twenty-four were initially assessed on no antiplatelet therapy, and then after 14d (N = 23) and 90d (N = 8) on aspirin monotherapy; 52 were assessed on aspirin monotherapy, and after 14 and 90 days on aspirin and dipyridamole combination therapy; 21 patients were assessed on aspirin and after 14 days (N = 21) and 90 days (N = 19) on clopidogrel. Peak thrombin generation and endogenous thrombin potential were reduced at 14 and 90 days (p ≤ 0.04) in the overall cohort. We assessed the impact of individual antiplatelet regimens on thrombin generation parameters to investigate the cause of this effect. Lag time and time-to-peak thrombin generation were unchanged at 14 days, but reduced 90 days after commencing aspirin (p ≤ 0.009). Lag time, peak thrombin generation and endogenous thrombin potential were reduced at both 14 and 90 days after adding dipyridamole to aspirin (p ≤ 0.01). Lag time was reduced 14 days after changing from aspirin to clopidogrel (p = 0.045), but this effect was not maintained at 90 days (p = 0.2). This pilot study did not show any consistent effects of commencing aspirin, or of changing from aspirin to clopidogrel on thrombin generation potential during follow-up. The addition of dipyridamole to aspirin led to a persistent reduction in peak and total thrombin generation ex vivo, and illustrates the diverse, potentially beneficial, newly recognised ‘anti-coagulant’ effects of dipyridamole in ischaemic CVD.
KeywordsThrombin generation potential TIA Stroke Aspirin Dipyridamole Clopidogrel Antiplatelet responsiveness
Dr Tobin’s research was funded by the IICN-Serono Fellowship, Meath Foundation, Lundbeck Neurosciences Bursary programme, and by unrestricted educational grant funding from Merck Serono Ireland, Brennan and Company, Ireland, and Biogen Idec Ireland Limited. Dr Kinsella’s research was funded by the Stanley Thomas Johnson Foundation, and by unrestricted educational grant funding from Bayer Schering Ireland, Pfizer Ireland and Elitech UK. Mr Kavanagh’s research was funded by the Health Research Board Ireland; Dr McCabe’s research programme was part-funded by grant support from the Programme for Research in Third Level Institutions in Ireland (Cycle 4), co-funded by the European Regional Development Fund.
Conflicts of interest
None of the authors report any conflicts of interest or other disclosures. None of the above charities or funding bodies had any influence on study design or conduct, data analysis or interpretation, or had any influence on the decision to submit the final manuscript for publication.
All human study must state that have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.
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