title: Thrombin formation and platelet activation at the site of vascular injury in patients with coronary artery disease treated with clopidogrel combined with aspirin.
abstract: BACKGROUND
  Data on the effects of oral antiplatelet agents on blood coagulation in vivo are conflicting. The platelet glycoprotein (GP) IIIa PlA2 allele has been suggested to modulate antithrombotic actions of clopidogrel.
  
  
  OBJECTIVE
  We investigated whether clopidogrel combined with aspirin affects local thrombin formation and platelet activation triggered by vascular injury.
  
  
  METHODS
  We studied patients with stable coronary artery disease on chronic aspirin therapy randomised to addition of clopidogrel 75 mg/d (n = 30) or continuation of aspirin 100 mg/d (n = 30) for 4 weeks. Markers of thrombin generation [thrombin-antithrombin complexes (TAT) and prothrombin 1.2 fragments (F1.2)] and markers of platelet activation [soluble CD40 ligand (sCD40L) and P-selectin] were determined in the supernatant of blood samples obtained from a microvascular injury site.
  
  
  RESULTS
  Total amounts of thrombin markers produced at the site of injury were similar before and after addition of clopidogrel, whereas platelet release of sCD40L and P-selectin was lower during treatment with aspirin + clopidogrel by 33.8% and 27.8% (p < 0.001), respectively. Patients in the highest tertile of reduction in platelet activation had previous myocardial infarction and peripheral arterial disease and released the highest amounts of sCD40L and P-selectin at baseline. TAT and F1.2 generation as well as sCD40L or P-selectin release were not influenced by the presence of the PlA2 allele.
  
  
  CONCLUSIONS
  Our study shows that clopidogrel combined with aspirin does not reduce thrombin formation following vascular injury, but attenuates platelet sCD40L and P-selectin release.
authors.affiliation: Instytut Kardiologii, Uniwersytet Jagielloński Collegium Medicum, ul. Pradnicka 80, 31-202 Krakow, Poland. mmundas@cyf-kr.edu.pl
authors.forename: Anetta
authors.initials: A
authors.lastname: Undas
authors.forename: Ewa
authors.initials: E
authors.lastname: Stepień
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Branicka
authors.forename: Paweł
authors.initials: P
authors.lastname: Wołkow
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Zmudka
authors.forename: Wiesława
authors.initials: W
authors.lastname: Tracz
mesh_terms: D001241:Aspirin / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D023201:CD40 Ligand / Q000378:metabolism; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood* / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006801:Humans; D022125:Lacerations; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011677:Punctures; D012867:Skin / Q000098:blood supply / Q000293:injuries; D013917:Thrombin / Q000096:biosynthesis*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014680:Veins / Q000293:injuries
chemical_list: D015415:Biomarkers; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D023201:CD40 Ligand; D000077144:Clopidogrel; D013917:Thrombin; D013988:Ticlopidine; D001241:Aspirin