Tissue factor expressed by adherent cells contributes to hemodialysis-membrane thrombogenicity.
Fiche publication
Date publication
août 2016
Journal
Thrombosis research
Auteurs
Membres identifiés du Cancéropôle Est :
Pr NGUYEN Philippe, Dr TERRYN Christine
Tous les auteurs :
Lakbakbi S, Debrumetz A, Terryn C, Szymezak J, Rieu P, Nguyen P
Lien Pubmed
Résumé
End-stage renal patients present a high risk of thrombosis and bleeding. Consequently, it is challenging to prevent clotting during hemodialysis. If a contact system induces thrombin generation in the extra corporeal circuit, recent data suggest a role of tissue factor (TF) in hemodialysis-associated thrombosis. Using a method of elution, we collected adhering cells to an acrylonitrile membrane layered by polythyleneimine (AN69-ST). Using optic microscopy and flow cytometry, we observed that adherent cells were mainly constituted by activated polymorphonuclear neutrophils (PMNs). Using a sensitive fluorogenic method of thrombin generation, we found that adhering cells triggered thrombin generation in a TF-dependent manner. We next identified the presence of TF mRNA (Q-PCR) in adhering cells. Using immunofluorescence, we observed the presence of TF in PMNs and of TF-decorated neutrophil extracellular traps (NETs). As TF triggers thrombin generation after binding to serine protease FVIIa, we evaluated the effect of an inactivated human recombinant factor VIIa (hrFVIIai) in a sheep model of hemodialysis (HD). One single bolus of hrFVIIai maintained the full patency of the hemodialysis circuit without any measurable systemic anticoagulant effect. TF is a promising target for preventing thrombosis during HD.
Référence
Thromb. Res.. 2016 Aug;144:218-23