PB0765 - Glycoprotein VI is an interesting target to prevent early stent thrombosis in different arterial territories

Monday, June 24, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Axelle Y. KERN, MSc

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

Co-Author(s)

DC

Dihia Chebbah

Biologist
University of Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, F-67065 Strasbourg, France
Strasbourg, Alsace, France
CR

Camille Robert

Master student
University of Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France
Strasbourg, Alsace, France
YK

Yevgeniy Kreinin

PhD candidate
Department of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa, Israel
Haïfa, Hefa, Israel
AL

Anne Lejay

Vascular Surgeon
Vascular Surgery and Renal Transplantation Department, Strasbourg University Hospitals, Strasbourg, France
Strasbourg, Alsace, France
SK

Salomé Kuntz

Vascular Surgeon
Vascular Surgery and Renal Transplantation Department, Strasbourg University Hospitals, Strasbourg, France
Strasbourg, Alsace, France
Martine Jandrot-Perrus, MD., PhD.

Researcher
Laboratory for Vascular Translational Science, UMR_S1148 INSERM, University Paris Cité, Hôpital Bichat, Paris, France
Paris, Ile-de-France, France
NC

Nabil Chakfé

Chief of Vascular Surgery
Vascular Surgery and Renal Transplantation Department, Strasbourg University Hospitals, Strasbourg, France
Strasbourg, Alsace, France
RP

Raoul Pop

Neuroradiologist
Interventional Neuroradiology 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
Haïfa, Hefa, Israel
PM

Pierre H. Mangin, PhD

Researcher
University of Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France
Strasbourg, Alsace, France

Background: Stent thrombosis (ST) is the most dangerous drawback of angioplasty, with an incidence reaching 1%, 6% and 18% in respectively the coronaries, femoral and the carotid arteries. It is associated with significant morbidity and mortality in all vascular territories. The variations of incidence are explained by the difference in antiplatelet regimen with dual-antiplatelet therapy (DAPT) used in coronary and femoral arteries and only aspirin in the carotid. Thus, there is a need to identify safe and efficient antithrombotic agents to reduce the burden of ST.

Aims: Our objective is to evaluate the role of GPVI in the prevention of ST in arteries from different vascular territories.

Methods: We developed on-scale macrofluidic flow chambers faithfully mimicking the human carotid, coronary or femoral artery. The chambers were coated with human atherosclerotic plaque homogenates (HAPH) and implanted with a stent. Hirudinated human whole blood was perfused through the chamber, and platelet aggregation studied using fluorescence and electron microscopy.

Results: Real-time video-microscopy showed that blood perfusion trough a carotid, coronary or femoral stented macrofluidic chamber coated with HAPH, resulted in thrombus formation. Thrombi formed exclusively in the stented regions coated with HAPH. Scanning electron microscopy showed that the platelets within the thrombi were highly activated, as evidenced by shape change with filopodia extension. DAPT (aspirin (50 µg/mL) + cangrelor (7.7 µg/mL)) efficiently prevented thrombus formation in coronary and femoral chambers. Aspirin alone also inhibited the formation of thrombi in the carotid model. Moreover, treating blood with glenzocimab (50µg/mL), an anti-GPVI agent, efficiently prevented platelet accumulation in all three models, suggesting that GPVI plays an important role in our experimental model of early ST.

Conclusion(s): Our results indicate that GPVI blockade efficiently prevented ST in various vascular chambers and under different rheological conditions, proposing glenzocimab as an attractive antithrombotic strategy, notably in patients with high risk of bleeding.