title: Regulation of PAR-1 in patients undergoing percutaneous coronary intervention: effects of unfractionated heparin and bivalirudin.
abstract: Aims We examined the specific effects of unfractionated heparin and bivalirudin on thrombin-inducible platelet PAR-1 in patients undergoing percutaneous coronary intervention (PCI). Methods and results To simulate in vivo conditions that may precipitate a bleeding event, we added thrombin in vitro to blood samples from 89 patients who had been randomly assigned to receive heparin or bivalirudin for elective PCI and examined thrombin-inducible PAR-1 expression. Thrombin-inducible cleavage of PAR-1 was inhibited by heparin, but not affected by bivalirudin (P = 0.0001). Further, PAR-1 internalization was more effectively inhibited by heparin than bivalirudin (P = 0.002). Conclusion Heparin has stronger inhibitory effects on thrombin-dependent PAR-1 cleavage and internalization, thus providing a biological explanation for lower clinical bleeding rates with bivalirudin.
authors.affiliation: Department of Internal Medicine 2, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Roza Badr
authors.initials: RB
authors.lastname: Eslam
authors.forename: Nina
authors.initials: N
authors.lastname: Reiter
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kaider
authors.forename: Sabine
authors.initials: S
authors.lastname: Eichinger
authors.forename: Irene M
authors.initials: IM
authors.lastname: Lang
authors.forename: Simon
authors.initials: S
authors.lastname: Panzer
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000379:methods; D000925:Anticoagulants / Q000627:therapeutic use*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006493:Heparin / Q000627:therapeutic use*; D006629:Hirudins; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D010446:Peptide Fragments / Q000627:therapeutic use*; D015539:Platelet Activation / Q000187:drug effects*; D044463:Receptor, PAR-1 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D005338:Fibrin Fibrinogen Degradation Products; D006629:Hirudins; D019007:P-Selectin; D010446:Peptide Fragments; D044463:Receptor, PAR-1; D011994:Recombinant Proteins; C036309:fibrin fragment D; D006493:Heparin; D013917:Thrombin; C074619:bivalirudin