[13] Geneva Platelet Group
The Geneva Platelet Group co-directed by Jean-Luc Reny and Pierre Fontana is an interdisciplinary group working with complementary approaches in a truly translational way on the issues of platelet function and antiplatelet drugs. Investigational approaches include basic science, pharmacological, clinical and epidemiological research.
Ongoing projects
- Antiplatelet Drug Resistances and Ischemic Events (ADRIE) : ancillary studies
The ADRIE study was an observational study on the clinical relevance of platelet reactivity in aspirin and clopidogrel treated cardiovascular patients. The corresponding biobank allows several studies to be performed, including collaborative studies in the field of pharmacogenetics within international consortium.
MicroRNAs (miRNAs) are promising biological markers and may also be involved in the regulation of sets of genes related to platelet function. The aim of this project is to functionally validate candidate miRNA in platelet function regulation using human platelets generated in vitro and a model of zebrafish to assess thrombus formation in vivo.
· PP2A and microRNA Regulation of Platelet Reactivity
This project aims to better understand why antiplatelet therapies show variable efficacy between patients. By combining human platelet models, microRNA analyses, clinical cohorts, and innovative zebrafish thrombosis models, our group investigates the role of the PP2A phosphatase complex and its regulators in platelet activation and thrombus formation. The ultimate goal is to identify novel biological mechanisms and biomarkers that could improve the personalization of antithrombotic therapies and help predict thrombotic or bleeding risk.
Patients treated with antithrombotics are at risk of both severe ischemic and bleeding events. However, current clinical scores are insufficiently discriminant to predict the most favorable drug and dosing for an improved net clinical benefit. Physiologically and population-based pharmacokinetic models (PBPK and POPPK respectively) incorporate substrate specific properties obtained from experimental in-vitro experiments as well as patients' demographic, genetic and physiological in vivo data in order to characterize the dose-concentration relationships. As such, they can be used to simulate and predict PK profiles accounting for specific patients' characteristics and are the basis of dosing optimization. These models could be a valuable tool to predict antithrombotic blood concentration in a given patient. The main goal of the OptimAT study is to elaborate predictive models characterizing the dose-concentration relationship with influencing variables of three direct oral anticoagulants (DOAC) (rivaroxaban, apixaban, dabigatran) and three P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) in hospitalized patients, which will serve as basis for drug selection and dosage optimization.
· Thrombus on RIVaroxaban and ASPirin – T-RivAsp project
This project investigates how dual pathway inhibition with low-dose rivaroxaban and aspirin influences clot formation and why treatment response varies between cardiovascular patients. By combining innovative in vitro assays with translational clinical studies, the project evaluates the impact of therapy on thrombus formation, clot contraction, and fibrinolysis, while identifying biomarkers associated with thrombotic and bleeding risk. The ultimate goal is to improve patient stratification and support more personalized antithrombotic treatment strategies in cardiovascular disease.
The Geneva Platelet Group is involved in several national international guidelines related to the perioperative management of antithrombotic drugs, haemophilia treatment and other bleeding disorders.