title: A comparison of anticoagulation with bivalirudin and provisional GPIIb/IIIa inhibition with unfractionated heparin and mandatory GPIIb/IIIa inhibition during percutaneous coronary intervention in relation to platelet activation and the inhibition of coagulation.
abstract: OBJECTIVE
  Our study sought to evaluate mechanisms of the current strategies for optimal anticoagulation during percutaneous coronary intervention (PCI).
  
  
  RESULTS
  Thirty-two high risk acute coronary syndrome patients were randomised to bivalirudin and provisional GPIIb/IIIa inhibition (GPIIb/IIIa) or unfractionated heparin (UFH) and mandatory GPIIb/IIIa. Flow cytometric measurements immediately after anticoagulation showed that, unlike UFH, bivalirudin did not activate platelets as indicated by P-selectin expression and fibrinogen binding while decreasing platelet-monocyte aggregates and monocyte expression of tissue factor. UFH released tissue factor pathway inhibitor (TFPI) during and immediately after PCI while bivalirudin (irrespective of GP IIb/IIIa) did not. Lower levels of TFPI with bivalirudin were seen during and immediately after PCI (P<0.01). Thrombin generation as indicated by prothrombin fragment F 1+2 levels was reduced during PCI in the UFH group (P<0.01) but not with bivalirudin. Soluble CD40 ligand is associated with thrombosis and levels were higher in the bivalirudin group irrespective of GPIIb/IIIa at the same stages (P<0.05).
  
  
  CONCLUSIONS
  Bivalirudin has some early advantages on platelet activation when compared to UFH. However, there are significant limitations in its mechanism of action, particularly a lack of release of tissue factor pathway inhibitor.
authors.affiliation: Pathology Queensland, The Prince Charles Laboratory Group, The Prince Charles Hospital, Queensland, Australia. michael_ray@health.qld.gov.au
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ray
authors.forename: Manjeet
authors.initials: M
authors.lastname: Juneja
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bett
authors.forename: Darren L
authors.initials: DL
authors.lastname: Walters
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects*; D023201:CD40 Ligand / Q000097:blood; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D006629:Hirudins / Q000009:adverse effects; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D015539:Platelet Activation / Q000187:drug effects*; D010973:Platelet Adhesiveness / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011516:Prothrombin; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D006629:Hirudins; D008074:Lipoproteins; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; C051928:lipoprotein-associated coagulation inhibitor; C045879:prothrombin fragment 1.2; D023201:CD40 Ligand; D011516:Prothrombin; D005340:Fibrinogen; D006493:Heparin; D013925:Thromboplastin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin; C074619:bivalirudin