PB0866 - Glycoprotein VI: an interesting target to prevent early stent thrombosis?

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

AK

Axelle KERN, MSc

PhD student
University of Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, F-67065 Strasbourg, France
STRASBOURG, Alsace, France

Co-Author(s)

DC

Dihia CHEBBAH

Intern
Strasbourg University Hospitals, Strasbourg, France
Strasbourg, Alsace, France
RP

Raoul Pop

Hospital practitioner
Interventional Neuroradiology Department, Strasbourg University Hospitals, Strasbourg, France
Strasbourg, Alsace, France
AL

Anne LEJAY

Hospital practitioner
Vascular Surgery and Renal Transplantation Department, Strasbourg University Hospitals, Strasbourg, France
Strasbourg, Alsace, France
NC

Nabil CHAKFE

Hospital practitioner
Vascular Surgery and Renal Transplantation Department, Strasbourg University Hospitals, Strasbourg, France
Strasbourg, Alsace, France
NK

Netanel KORIN

Associate Professor
Department of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa, Israel
Haifa, Hefa, Israel
PM

Pierre Mangin

Research Director
Université de Strasbourg, INSERM, EFS Grand Est, BPPS UMR-S1255, FMTS, F-67065 Strasbourg, France
Strasbourg, Alsace, France

Background: Stenting improves recanalization rates and clinical outcomes in patients with a stenosed artery due to the presence of an atherosclerotic plaque. Dual-antiplatelet therapy (DAPT) is the treatment of choice to prevent stent thrombosis (ST), except in acute ischemic stroke patients in which only aspirin is recommended to avoid haemorrhagic transformation. As a consequence, early ST occurs in 20% of patients worsening clinical outcome. Concerning the femoral artery, the incidence of ST reaches 6% despite the use of DAPT. There is a need to identify safer anti-thrombotic agents to prevent ST.

Aims: The objective of this study is to evaluate the potential of glenzocimab, a glycoprotein (GP) VI blocker, to prevent ST in comparison to conventional anti-platelet therapies.

Methods: We developed on-scale macrofluidic flow chambers mimicking a human carotid or femoral artery. The chambers were coated with human atherosclerotic plaque (HAP) homogenates from relevant arteries before inserting a stent. Hirudinated human blood was perfused through the chamber, and platelet aggregation was studied using fluorescence and electron microscopy. The effect of glenzocimab on the prevention of ST was compared to other anti-platelet agents.

Results: Real-time video-microscopy showed that hirudinated human whole blood perfused at physiological flows through a carotid or a femoral stented macrofluidic device coated with HAP homogenate, resulted in the formation of platelet thrombi. Thrombi in both chambers formed exclusively in the stented regions that were coated with HAP. Electron microscopy showed that the platelets within the thrombi were highly activated, as evidenced by shape change with filopodia extension. Use of aspirin, the standard of care, showed a reduction in thrombus formation in both models. Moreover, treating blood with glenzocimab also resulted in a marked decrease in platelet accumulation, suggesting that GPVI plays an important role in early ST.

Conclusion(s): Our results indicate that GPVI is a potentially interesting target to prevent ST.