Le groupe “Nouvelles voies physiopathologiques impliquées dans la thrombose” vient de publier une revue dans Journal of Thrombosis and Haemostasis.
Le test de génération de thrombine offre une vue d’ensemble de l’équilibre hémostatique. Par des approches multi-omiques (analyse protéomique de 236 protéines dans deux populations et données de GWAS) et fonctionnelles, cette étude a identifié les protéines du complément C5 et C9 comme des déterminants de la génération de thrombine.
+Plasma levels of complement components C5 and C9 are associated with thrombin generation.
Vacik Díaz R, Munsch G, Iglesias MJ, Pallares Robles A, Ibrahim-Kosta M, Nourse J, Khan E, Castoldi E, Saut N, Boland A, Germain M, Deleuze JF, Odeberg J, Morange PE, Danckwardt S, Tregouët DA, Goumidi L
Background
The thrombin generation assay (TGA) evaluates the potential of plasma to generate thrombin over time, providing a global picture of an individual’s hemostatic balance.
Objectives
This study aimed to identify novel biological determinants of thrombin generation using a multiomics approach.
Methods
Associations between TGA parameters and plasma levels of 377 antibodies targeting 236 candidate proteins for cardiovascular risk were tested using multiple linear regression analysis in 770 individuals with venous thrombosis from the Marseille Thrombosis Association (MARTHA) study. Proteins associated with at least 3 TGA parameters were selected for validation in an independent population of 536 healthy individuals (Etablissement Français du Sang Alpes-Méditerranée [EFS-AM]). Proteins with strongest associations in both groups underwent additional genetic analyses and in vitro experiments.
Results
Eighteen proteins were associated (P < 1.33 × 10⁻4) with at least 3 TGA parameters in MARTHA, among which 13 demonstrated a similar pattern of associations in EFS-AM. Complement proteins C5 and C9 had the strongest associations in both groups. Ex vivo supplementation of platelet-poor plasma with purified C9 protein had a significant dose-dependent effect on TGA parameters. No effect was observed with purified C5.
Several single nucleotide polymorphisms associated with C5 and C9 plasma levels were identified, with the strongest association for the C5 missense variant rs17611, which was associated with a decrease in C5 levels, endogenous thrombin potential, and peak in MARTHA. No association of this variant with TGA parameters was observed in EFS-AM.
Conclusion
This study identified complement proteins C5 and C9 as potential determinants of thrombin generation. Further studies are warranted to establish causality and elucidate the underlying mechanisms.