title: Residual thrombin generation potential is inversely linked to the occurrence of atherothrombotic events in patients with peripheral arterial disease.
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.
  
  
  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.
authors.affiliation: Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gremmel
authors.forename: Renate
authors.initials: R
authors.lastname: Koppensteiner
authors.forename: Cihan
authors.initials: C
authors.lastname: Ay
authors.forename: Simon
authors.initials: S
authors.lastname: Panzer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000800:Angioplasty, Balloon; D001792:Blood Platelets / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000401:mortality; D000077144:Clopidogrel; D015331:Cohort Studies; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction; D019007:P-Selectin / Q000378:metabolism*; D010446:Peptide Fragments; D058729:Peripheral Arterial Disease / Q000097:blood / Q000628:therapy*; D015539:Platelet Activation / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D044463:Receptor, PAR-1; D012008:Recurrence; D015607:Stents; D020521:Stroke; D013917:Thrombin / Q000502:physiology*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D019007:P-Selectin; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D044463:Receptor, PAR-1; C082835:thrombin receptor peptide (42-47); D000077144:Clopidogrel; D013917:Thrombin; D013988:Ticlopidine
keywords: Angioplasty; peripheral arterial disease; stent implantation; thrombin generation potential