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.

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.