title: Bivalirudin is a dual inhibitor of thrombin and collagen-dependent platelet activation in patients undergoing percutaneous coronary intervention.
abstract: BACKGROUND
  Bivalirudin, a direct thrombin inhibitor, is a widely used adjunctive therapy in patients undergoing percutaneous intervention (PCI). Thrombin is a highly potent agonist of platelets and activates the protease-activated receptors, PAR1 and PAR4, but it is not known whether bivalirudin exerts antiplatelet effects in PCI patients. We tested the hypothesis that bivalirudin acts as an antiplatelet agent in PCI patients by preventing activation of PARs on the platelet surface.
  
  
  RESULTS
  The effect of bivalirudin on platelet function and systemic thrombin levels was assessed in patients undergoing elective PCI. Mean plasma levels of bivalirudin were 2.7±0.5 μmol/L during PCI, which correlated with marked inhibition of thrombin-induced platelet aggregation and significantly inhibited cleavage of PAR1. Unexpectedly, bivalirudin also significantly inhibited collagen-platelet aggregation during PCI. Collagen induced a conversion of the platelet surface to a procoagulant state in a thrombin-dependent manner that was blocked by bivalirudin. Consistent with this result, bivalirudin reduced systemic thrombin levels by >50% during PCI. Termination of the bivalirudin infusion resulted in rapid clearance of the drug with a half-life of 29.3 minutes.
  
  
  CONCLUSIONS
  Bivalirudin effectively suppresses thrombin-dependent platelet activation via inhibition of PAR1 cleavage and inhibits collagen-induced platelet procoagulant activity as well as systemic thrombin levels in patients undergoing PCI.
authors.affiliation: The Cardiac Catheterization Laboratory, Division of Cardiology, Tufts Medical Center, Boston, Massachusetts 02111, USA.
authors.forename: Carey
authors.initials: C
authors.lastname: Kimmelstiel
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Navin K
authors.initials: NK
authors.lastname: Kapur
authors.forename: Andrew
authors.initials: A
authors.lastname: Weintraub
authors.forename: Barath
authors.initials: B
authors.lastname: Krishnamurthy
authors.forename: Vilma
authors.initials: V
authors.lastname: Castaneda
authors.forename: Lidija
authors.initials: L
authors.lastname: Covic
authors.forename: Athan
authors.initials: A
authors.lastname: Kuliopulos
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000990:Antithrombin III; D000991:Antithrombins / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology; D005260:Female; D006629:Hirudins / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000493:pharmacokinetics / Q000494:pharmacology*; D010447:Peptide Hydrolases / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D044463:Receptor, PAR-1 / Q000378:metabolism; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D044463:Receptor, PAR-1; D011994:Recombinant Proteins; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D003094:Collagen; D010447:Peptide Hydrolases; C074619:bivalirudin