Bivalirudin inhibits periprocedural platelet function and tissue factor expression of human smooth muscle cells.
OBJECTIVE
A major concern of stent implantation after percutaneous coronary intervention (PCI) is acute stent thrombosis. Effective inhibition of periprocedural platelet function in patients with coronary artery disease (CAD) leads to an improved outcome. In this study, we examined the periprocedural platelet reactivity after administrating bivalirudin during PCI compared to unfractionated heparin (UFH) administration. Further, the effect of bivalirudin on induced tissue factor (TF) expression in smooth muscle cells (SMC) was determined.


METHODS
Patients with CAD (n = 58) and double antithrombotic medication were treated intraprocedural with UFH (n = 30) or bivalirudin (n = 28). Platelet activation markers were flow cytometrically measured before and after stenting. The expression of TF in SMC was determined by real-time PCR and Western blotting. The thrombogenicity of platelet-derived microparticles and SMC was assessed via a TF activity assay.


RESULTS
Bivalirudin significantly diminished the agonist-induced platelet reactivity post-PCI. Compared to UFH treatment, the adenosine diphosphate (ADP) and thrombin receptor-activating peptide (TRAP)-induced thrombospondin expression post-PCI was reduced when bivalirudin was administrated during intervention. In contrast to UFH, bivalirudin reduced the P-selectin expression of unstimulated and ADP-induced platelets post-PCI. Moreover, bivalirudin inhibited the thrombin-, but not FVIIa- or FVIIa/FX-induced TF expression and pro-coagulant TF activity of SMC. Moreover, bivalirudin reduced the TF activity of platelet-derived microparticles postinduction with TRAP or ADP.


CONCLUSIONS
Bivalirudin is better than UFH in reducing periprocedural platelet activation. Moreover, thrombin-induced TF expression is inhibited by bivalirudin. Thus, bivalirudin seems to be a better anticoagulant during PCI than UFH.
Charitè - Universitätsmedizin Berlin, Campus Benjamin Franklin, Centrum für Herz- und Kreislaufmedizin, Berlin, Germany.
Wojciech
W
Pepke
Andreas
A
Eisenreich
Markus
M
Jaster
Yunus
Y
Ayral
Peter
P
Bobbert
Alexander
A
Mayer
Heinz-Peter
HP
Schultheiss
Ursula
U
Rauch
D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D000991:Antithrombins / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000097:blood / Q000628:therapy*; D015942:Factor VIIa / Q000378:metabolism; D005170:Factor X / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005858:Germany; D006493:Heparin / Q000627:therapeutic use; D006629:Hirudins; D006801:Humans; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D019007:P-Selectin / Q000097:blood; D010446:Peptide Fragments / Q000627:therapeutic use*; D062645:Percutaneous Coronary Intervention / Q000295:instrumentation; D015539:Platelet Activation / Q000187:drug effects*; D010979:Platelet Function Tests; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015607:Stents; D060149:Tetraspanin 30 / Q000097:blood; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D019699:Thrombospondins / Q000097:blood; D016896:Treatment Outcome
D000925:Anticoagulants; D000991:Antithrombins; D015415:Biomarkers; C554586:CD63 protein, human; D006629:Hirudins; D019007:P-Selectin; D010446:Peptide Fragments; D012333:RNA, Messenger; D011994:Recombinant Proteins; C546937:SELP protein, human; D060149:Tetraspanin 30; D019699:Thrombospondins; D005170:Factor X; D006493:Heparin; D013925:Thromboplastin; D015942:Factor VIIa; C074619:bivalirudin