Journal of Thrombosis and Thrombolysis

, Volume 30, Issue 4, pp 412–418

Differential inhibitory effect of fondaparinux on the procoagulant potential of intact monocytes and monocyte-derived microparticles

  • Sonia Ben-Hadj-Khalifa-Kechiche
  • Nathalie Hezard
  • Stephane Poitevin
  • Marie-Geneviève Remy
  • Bernadette Florent
  • Touhami Mahjoub
  • Philippe Nguyen
Article

Abstract

Monocytes and monocyte-derived microparticles (MMPs) play a major role in acute coronary syndrome (ASC). Activated monocytes (ac-M) and MMPs support thrombin generation via tissue factor (TF). The aim of this study was to evaluate the inhibitory effect of fondaparinux, a selective Xa inhibitor, on thrombin generation supported by activated monocytes and MMPs. Monocytes were purified by elutriation. They were activated by LPS, allowing to obtain both ac-M and MMPs. Thrombin generation was performed using Fluoroscan® in these two cell models, in comparison with a cell-free model (TF 5 pM final). Two concentrations of ac-M (0.2 × 106 and 1 × 106/well) and four concentrations of MMPs (40,000; 80,000; 120,000 and 160,000/well) were tested. TGT was evaluated for increasing fondaparinux concentrations (0, 0.1, 0.4, 0.7 and 1.2 μg/ml). Without fondaparinux, 0.2 × 106 ac-M and 160,000 MMPs induced comparable results. Fondaparinux inhibited thrombin generation in the three models. Inhibition was fondaparinux concentration dependent. Rate index was the most sensitive parameter, compared to lag-time, peak and endogenous thrombin potential. The rate index IC50 were 0.69 ± 0.03 μg/ml for ac-M, 0.20 ± 0.03 μg/ml for MMPs, and 0.22 ± 0.02 μg/ml for cell-free model. Fondaparinux exerted an inhibitory effect at all concentrations, including the lowest (0.1 μg/ml). The extend of inhibition was similar between MMPs and cell-free models, and stronger than ac-M model. We assume that the efficacy of fondaparinux 2.5 mg once daily in ACS patients may be in part attributed to its inhibitory effect on MMPs.

Keywords

Fondaparinux Thrombin generation Monocyte Monocyte-derived microparticle Tissue factor 

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Sonia Ben-Hadj-Khalifa-Kechiche
    • 1
    • 3
  • Nathalie Hezard
    • 1
    • 2
  • Stephane Poitevin
    • 4
  • Marie-Geneviève Remy
    • 1
  • Bernadette Florent
    • 1
  • Touhami Mahjoub
    • 3
  • Philippe Nguyen
    • 1
    • 2
  1. 1.Laboratoire d’HématologieCHU Robert DebréReims CedexFrance
  2. 2.EA-3801, Faculté de MédecineUniversité Reims-Champagne ArdenneReimsFrance
  3. 3.Faculté de PharmacieUnité de Recherche des Maladies Hématologiques et Auto-ImmunesMonastirTunisie
  4. 4.Faculté de PharmacieINSERM UMR-S 608, Physiopathologie de l’EndothéliumMarseilleFrance

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