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  • Title: Residual thrombin generation potential is inversely linked to the occurrence of atherothrombotic events in patients with peripheral arterial disease.
    Author: Gremmel T, Koppensteiner R, Ay C, Panzer S.
    Journal: Eur J Clin Invest; 2014; 44(3):319-24. PubMed ID: 24382127.
    Abstract:
    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.
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