Bridget Egan

High on-treatment platelet reactivity on commonly prescribed antiplatelet agents following transient ischaemic attack or ischaemic stroke: results from the Trinity Antiplatelet Responsiveness (TRAP) study

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

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.

Increased platelet activation in early symptomatic vs. asymptomatic carotid stenosis and relationship with microembolic status: results from the Platelets and Carotid Stenosis Study

Cerebral microembolic signals (MES) may predict increased stroke risk in carotid stenosis. However, the relationship between platelet counts or platelet activation status and MES in symptomatic vs. asymptomatic carotid stenosis has not been comprehensively assessed.

Increased endothelial activation in recently symptomatic versus asymptomatic carotid artery stenosis and in cerebral microembolic-signal-negative patient subgroups

von Willebrand factor propeptide (VWF:Ag II) is potentially a more sensitive marker of acute endothelial activation than von Willebrand factor antigen (VWF:Ag). These biomarkers have not been simultaneously assessed in asymptomatic versus symptomatic carotid stenosis patients. The relationship between endothelial activation and cerebral microembolic signals (MESs) detected on transcranial Doppler ultrasound is unknown.

Increased thrombin generation potential in symptomatic versus asymptomatic moderate or severe carotid stenosis and relationship with cerebral microemboli

Introduction The importance of thrombin generation in the pathogenesis of TIA or stroke and its relationship with cerebral microembolic signals (MES) in asymptomatic and symptomatic carotid stenosis has not been comprehensively assessed. Methods Plasma thrombin generation parameters from patients with moderate or severe (≥50%) asymptomatic carotid stenosis were compared with those from patients with symptomatic carotid stenosis in the early (≤4 weeks) and late phases (≥3 months) after TIA or stroke in this prospective, pilot observational study. Thrombin generation profile was longitudinally assessed in symptomatic patients with data at each time point. Bilateral transcranial Doppler ultrasound monitoring of the middle cerebral arteries was performed whenever possible to classify patients as MES-positive or MES-negative. Results Data from 31 asymptomatic, 46 ‘early symptomatic’ and 35 ‘late symptomatic’ patients were analysed. Peak thrombin (344.2 nM vs 305.3 nM; p=0.01) and endogenous thrombin potential (1772.4 vs 1589.7; p=0.047) were higher in early symptomatic than asymptomatic patients. Peak thrombin production decreased in symptomatic patients followed up from the early to late phase after TIA or stroke (339.7 nM vs 308.6 nM; p=0.02). Transcranial Doppler ultrasound data were available in 25 asymptomatic, 31 early symptomatic and 27 late symptomatic patients. Early symptomatic MES-positive patients had a shorter ‘time-to-peak thrombin’ than asymptomatic MES-positive patients (p=0.04), suggesting a more procoagulant state in this early symptomatic subgroup. Discussion Thrombin generation potential is greater in patients with recently symptomatic than asymptomatic carotid stenosis, and decreases over time following TIA or stroke associated with carotid stenosis. These data improve our understanding of the haemostatic/thrombotic biomarker profile in moderate-severe carotid stenosis.