title: Association of thrombin generation potential with platelet PAR-1 regulation and P-selectin expression in patients on dual antiplatelet therapy.
abstract: We studied the association of thrombin generation potential with platelet protease activated receptor (PAR)-1 regulation and platelet activation in 52 stable coronary artery disease patients on continuous therapy with aspirin and clopidogrel (n = 42) or prasugrel (n = 10). Compared to controls, peak thrombin generation potential was elevated in only 11 patients (p > 0.05), while F1.2 was elevated in 26 patients (p < 0.0001). PAR-1 and thrombin inducible P-selectin expression were significantly elevated in patients compared to controls (p < 0.001). There were no significant correlations between levels of thrombin generation potential or F1.2 and PAR-1 regulation. However, there was a significant inverse correlation between levels of peak thrombin generation potential and in vitro thrombin-inducible expression of P-selectin (p = 0.002), suggesting in vivo depletion of platelet alpha granules due to ongoing platelet activation.
authors.affiliation: Department of Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Roza
authors.initials: R
authors.lastname: Badr Eslam
authors.forename: Florian
authors.initials: F
authors.lastname: Posch
authors.forename: Irene M
authors.initials: IM
authors.lastname: Lang
authors.forename: Thomas
authors.initials: T
authors.lastname: Gremmel
authors.forename: Beate
authors.initials: B
authors.lastname: Eichelberger
authors.forename: Cihan
authors.initials: C
authors.lastname: Ay
authors.forename: Simon
authors.initials: S
authors.lastname: Panzer
mesh_terms: D000328:Adult; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D016022:Case-Control Studies; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood; D010879:Piperazines / Q000008:administration & dosage*; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D000068799:Prasugrel Hydrochloride; D011516:Prothrombin; D044463:Receptor, PAR-1 / Q000097:blood*; D013876:Thiophenes / Q000008:administration & dosage*; D013917:Thrombin / Q000378:metabolism*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D015415:Biomarkers; D019007:P-Selectin; D010446:Peptide Fragments; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D044463:Receptor, PAR-1; C546937:SELP protein, human; D013876:Thiophenes; C045879:prothrombin fragment 1.2; D011516:Prothrombin; D000077144:Clopidogrel; D013917:Thrombin; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; D001241:Aspirin