Enhanced ex vivo inhibition of platelet function following addition of dipyridamole to aspirin after transient ischaemic attack or ischaemic stroke: first results from the TRinity AntiPlatelet responsiveness (TrAP) study.

Ex vivo dipyridamole 'non-responsiveness' has not been extensively studied in ischaemic cerebrovascular disease. Platelet surface marker expression, leucocyte-platelet complex formation and inhibition of platelet function at high shear stress as detected by the PFA-100® Collagen-Adenosine-diphosphate (C-ADP) and Collagen-Epinephrine cartridges was assessed in 52 patients within 4 weeks of transient ischaemic attack (TIA) or ischaemic stroke on aspirin, and then 14 d (14 d) and >90 d (90 d) after adding dipyridamole. A novel definition of 'Dipyridamole non-responsiveness' was used. The median C-ADP closure time increased following addition of dipyridamole, remained elevated at 90 d (P ≤ 0·03), and was unaffected by aspirin dose. 59% at 14 d and 56% at 90 d were 'dipyridamole non-responders' on the PFA-100. The proportion of non-responders at 14 and 90 d was similar (P= 0·9). Compared with baseline (4·6%), median monocyte-platelet complexes increased at 14 d (5·0%, P= 0·03) and 90 d (4·9%, P= 0·04). Low C-ADP closure times were associated with increased monocyte-platelet complexes at 14 d (r= -0·32, P= 0·02) and 90 d (r= -0·33, P = 0·02). Monocyte-platelet complexes increased in the subgroup of dipyridamole non-responders on the PFA-100 (P≤ 0·045), but not in responders (P ≥ 0·5), at 14 and 90 d versus baseline. Additional inhibition of platelet function has been detected with the PFA-100 when dipyridamole is added to aspirin. Elevated monocyte-platelet complexes may contribute to ex vivo dipyridamole non-responsiveness.