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Residual thrombin generation potential is inversely linked to the occurrence of atherothrombotic events in patients with peripheral arterial disease
Author(s) -
Gremmel Thomas,
Koppensteiner Renate,
Ay Cihan,
Panzer Simon
Publication year - 2014
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.12236
Subject(s) - medicine , thrombin , cardiology , platelet activation , thrombin receptor , angioplasty , myocardial infarction , platelet , stroke (engine) , mechanical engineering , engineering
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 .