Residual thrombin generation potential is inversely linked to the occurrence of atherothrombotic events in patients with peripheral arterial disease.

THROMBIN; THROMBOSIS; PERIPHERAL vascular diseases; SERINE proteinases; PROTEASE-activated receptors; BLOOD platelet activation; ANGIOPLASTY

Background The serine protease thrombin is the most potent platelet agonist and acts mainly via protease-activated receptors ( PAR)-1 and -4. Data linking in vitro thrombin generation potential with PAR-1-mediated platelet activation and adverse events after angioplasty and stenting are missing, so far. Materials and methods In this prospective cohort study, thrombin generation potential was measured with a commercially available assay in 108 patients undergoing infrainguinal angioplasty and stenting for lower extremity artery disease classified as Rutherford stages of peripheral arterial disease ( PAD) 2-3. Thrombin receptor-activating peptide ( TRAP)-6-inducible P-selectin expression was determined by flow cytometry. Results One hundred and four patients entered statistical analysis. Peak thrombin generation potential correlated inversely with TRAP-6-inducible P-selectin ( r = −0·2, P < 0·05). Target vessel restenosis or reocclusion (TVR) occurred in 37 patients (35·6%), and the composite atherothrombotic endpoint of myocardial infarction, ischaemic stroke or transient ischaemic attack, and cardiovascular death occurred in seven patients (6·7%) within 2-year follow-up. Peak thrombin generation was similar between patients without and with TVR [465 nM (354-566 nM) vs. 440 nM (355-523 nM), P = 0·6], but significantly lower in patients with the atherothrombotic endpoint than in patients without atherothrombotic events [357 nM (219-389 nM) vs. 463 nM (362-55 nM), P = 0·03]. Further, low thrombin generation potential was associated with an 11·7-fold (95% CI 1·4-97·6; P = 0·02) increased risk of future atherothrombotic events. Conclusions Residual thrombin generation potential is inversely correlated with PAR-1-mediated platelet activation and linked to the occurrence of atherothrombotic events in patients with PAD. [ABSTRACT FROM AUTHOR]