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 4weeks of transient ischaemic attack (TIA) or ischaemic stroke on aspirin, and then 14d (14d) and >90d (90d) 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 90d (P≤0·03), and was unaffected by aspirin dose. 59% at 14d and 56% at 90d were 'dipyridamole non-responders' on the PFA-100. The proportion of non-responders at 14 and 90d was similar (P=0·9). Compared with baseline (4·6%), median monocyte-platelet complexes increased at 14d (5·0%, P=0·03) and 90d (4·9%, P=0·04). Low C-ADP closure times were associated with increased monocyte-platelet complexes at 14d (r=-0·32, P=0·02) and 90d (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 90d 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.