title: Comparative study of the effect of rivaroxaban and fondaparinux on monocyte's coagulant activity and cytokine release.
abstract: OBJECTIVE
  Tissue factor (TF) exposed on activated monocytes and macrophages is involved in thrombosis through activation of factor X and cytokine release, responsible for inflammation and thrombosis. We investigated the effect of two anti-factor Xa drugs: rivaroxaban, a direct anti-Xa inhibitor, and fondaparinux, an antithrombin dependent anti-Xa inhibitor, on monocyte/macrophage procoagulant activity and cytokine release.
  
  
  METHODS
  Rivaroxaban and fondaparinux were tested at pharmacological concentrations on LPS-activated monocytes and on THP-1 cells, a human monocytic cell line, to assess 1) TF expression by flow cytometry 2) prothrombinase activity by its coagulant activity and 3) cytokine release in cell supernatants by antibody based cytokine array and ELISA for IL-8 and TNFα.
  
  
  CONCLUSIONS
  Rivaroxaban and fondaparinux did not modify TF expression level on activated cells. In contrast procoagulant activity associated to monocytes and macrophages was dose dependently inhibited by rivaroxaban, but not significantly by fondaparinux. These results could explain why patients undergoing major orthopedic surgery with rivaroxaban prophylaxis were able to achieve significant reductions in venous thromboembolism, compared with drugs commonly used, i.e. fondaparinux and low molecular weight heparin. In addition, rivaroxaban and fondaparinux suppressed some chemokine secretion produced by activated macrophages. This may also contribute to their antithrombotic effect in clinic.
authors.affiliation: Laboratory MERCI (EA 3829), Faculty of Medicine and Pharmacy, CHU Rouen, Rouen, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Laurent
authors.affiliation: Laboratory MERCI (EA 3829), Faculty of Medicine and Pharmacy, CHU Rouen, Rouen, France.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Joimel
authors.affiliation: Laboratory MERCI (EA 3829), Faculty of Medicine and Pharmacy, CHU Rouen, Rouen, France.|INSERM UMR 965, Lariboisiere Hospital, University of Paris Diderot, Paris, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Varin
authors.affiliation: Laboratory MERCI (EA 3829), Faculty of Medicine and Pharmacy, CHU Rouen, Rouen, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Cazin
authors.affiliation: Laboratory MERCI (EA 3829), Faculty of Medicine and Pharmacy, CHU Rouen, Rouen, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Gest
authors.affiliation: Laboratory MERCI (EA 3829), Faculty of Medicine and Pharmacy, CHU Rouen, Rouen, France.
authors.forename: Veronique
authors.initials: V
authors.lastname: Le-Cam-Duchez
authors.affiliation: INSERM UMR_S1165, IUH, University of Paris Diderot, Saint Louis Hospital, Paris, France.|School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122 China.
authors.forename: Jian
authors.initials: J
authors.lastname: Jin
authors.affiliation: INSERM UMR_S1165, IUH, University of Paris Diderot, Saint Louis Hospital, Paris, France.|Research center of Tissue engineering and stem cells, Guiyang Medical University, 550004 Guiyang, China.
authors.forename: Jielin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Laboratory MERCI (EA 3829), Faculty of Medicine and Pharmacy, CHU Rouen, Rouen, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vannier
authors.affiliation: INSERM UMR_S1165, IUH, University of Paris Diderot, Saint Louis Hospital, Paris, France.
authors.forename: He
authors.initials: H
authors.lastname: Lu
authors.affiliation: INSERM UMR 965, Lariboisiere Hospital, University of Paris Diderot, Paris, France.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Soria
authors.affiliation: Laboratory MERCI (EA 3829), Faculty of Medicine and Pharmacy, CHU Rouen, Rouen, France.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Laboratory MERCI (EA 3829), Faculty of Medicine and Pharmacy, CHU Rouen, Rouen, France.
authors.forename: Claudine
authors.initials: C
authors.lastname: Soria
keywords: Coagulant; Cytokine; Fondaparinux; Monocyte; Rivaroxaban