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Keywords:

  • aspirin;
  • clopidogrel;
  • flow cytometry;
  • high on-treatment platelet reactivity;
  • platelet function analyser-100;
  • stroke;
  • transient ischaemic attack

Background and purpose

The prevalence of ex vivo ‘high on-treatment platelet reactivity’ (HTPR) to antiplatelet regimens in patients with ischaemic cerebrovascular disease (CVD) is uncertain.

Methods

HTPR was assessed with PFA-100 collagen-epinephrine (C-EPI) and collagen-ADP (C-ADP) cartridges. Platelet activation (CD62P, CD63 and leucocyte–platelet complex formation) was assessed with whole-blood flow cytometry. Patients were assessed at baseline [≤4 weeks of transient ischaemic attack (TIA) or ischaemic stroke], and at 14 days and ≥90 days after changing treatment from (i) no medication to aspirin monotherapy (N = 26) or (ii) aspirin to clopidogrel monotherapy (N = 22). HTPR was defined in a novel, ‘longitudinal fashion’ as failure to prolong relevant closure times compared with the patient's ‘baseline value’ before he/she underwent an antiplatelet change by more than twice the coefficient of variation of the assay.

Results

(i) C-EPI closure times increased at 14 days and 90 days after commencing aspirin (P = 0.002); 24% at 14 days and 18% at 90 days demonstrated HTPR on aspirin. (ii) C-ADP closure times increased at 14 days (P = 0.001) but not 90 days (P = 0.09) after changing from aspirin to clopidogrel; 41% at 14 days, and 35% at 90 days demonstrated HTPR on clopidogrel. Platelet activation was unaffected by aspirin (P = 0.09). The percentage neutrophil–platelet complexes decreased at 14 days (P = 0.02), but this reduction was not maintained 90 days after changing to clopidogrel (P = 0.3). No patient had a recurrent vascular event during prospective follow-up.

Conclusions

Longitudinal definitions of HTPR in patients with ischaemic CVD who are undergoing a change in antiplatelet therapy have the potential to provide more clinically meaningful information than traditional ‘cross-sectional definitions’ of HTPR which are usually based on the comparison of patients’ values with those in healthy controls. Using our novel, longitudinal definition of HTPR, the PFA-100 could be used to monitor ex vivo responsiveness to aspirin, and larger, prospective studies are warranted to assess the clinical predictive value of this and other platelet function tests in patients with ischaemic CVD.