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.
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.
Ray
Michael J
MJ
Pathology Queensland, The Prince Charles Laboratory Group, The Prince Charles Hospital, Queensland, Australia. michael_ray@health.qld.gov.au
Juneja
Manjeet
M
Bett
Nicholas
N
Walters
Darren L
DL
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
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