Tissue factor expressed by adherent cells contributes to hemodialysis-membrane thrombogenicity. Issue 144 (August 2016)

• Record Type: Journal Article
• Authors: Lakbakbi, Souad; Debrumetz, Alexandre; Terryn, Christine; Szymezak, Jean; Rieu, Philippe; Nguyen, Philippe
• Is Part Of: Thrombosis research. Issue 144(2016)
• Page Start: 218
• Page End: 223
• Publication Date: 2016-08
• Subjects: Hemodialysis -- Anticoagulation -- Cell activation -- Tissue factor; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2016.05.017
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: 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. Highlights: Adherent cells to hemodialysis membrane AN69-ST are mainly constituted of activated neutrophils. Tissue factor expressed by adherent cells contributes to membrane thrombogenicity. Inhibiting Tissue factor prevent clotting during haemodialysis.