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Ferric Chloride-induced Murine Thrombosis Models
Published on: September 5, 2016
Bivalirudin inhibits periprocedural platelet function and tissue factor expression of human smooth muscle cells
Wojciech Pepke1, Andreas Eisenreich, Markus Jaster
1Charitè - Universitätsmedizin Berlin, Campus Benjamin Franklin, Centrum für Herz- und Kreislaufmedizin, Berlin, Germany.
Insights
Bivalirudin significantly reduces platelet activation and tissue factor expression during percutaneous coronary intervention (PCI) compared to unfractionated heparin (UFH). This suggests bivalirudin is a more effective anticoagulant for PCI in patients with coronary artery disease (CAD).
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Hematology
Background:
- Acute stent thrombosis is a significant risk following percutaneous coronary intervention (PCI).
- Effective inhibition of platelet function during PCI improves outcomes in patients with coronary artery disease (CAD).
- Unfractionated heparin (UFH) is commonly used, but alternative anticoagulants are being investigated.
Purpose of the Study:
- To compare the periprocedural platelet reactivity between bivalirudin and UFH during PCI.
- To evaluate the effect of bivalirudin on tissue factor (TF) expression in smooth muscle cells (SMC).
- To assess the impact of these anticoagulants on platelet-derived microparticles and SMC thrombogenicity.
Main Methods:
- A randomized study involving 58 patients with CAD receiving either UFH (n=30) or bivalirudin (n=28) during PCI.
- Flow cytometry was used to measure platelet activation markers pre- and post-stenting.
- Real-time PCR, Western blotting, and TF activity assays assessed TF expression and activity in SMC and microparticles.
Main Results:
- Bivalirudin significantly reduced agonist-induced platelet reactivity post-PCI compared to UFH.
- Bivalirudin decreased P-selectin expression and thrombospondin release induced by ADP and TRAP.
- Bivalirudin inhibited thrombin-induced TF expression and pro-coagulant TF activity in SMC and microparticles.
Conclusions:
- Bivalirudin demonstrates superior efficacy over UFH in mitigating periprocedural platelet activation during PCI.
- Bivalirudin effectively inhibits thrombin-induced tissue factor expression, contributing to its anticoagulant properties.
- Bivalirudin represents a potentially more advantageous anticoagulant strategy for patients undergoing PCI.
Aim:
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.
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