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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Differential inhibitory effect of fondaparinux on the procoagulant potential of intact monocytes and monocyte-derived microparticles
Journal of Thrombosis and Thrombolysis, Volume 30, No. 4, Year 2010
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Description
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 9 106 and 1 9 106/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 9 106 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. © Springer Science+Business Media, LLC 2010.
Authors & Co-Authors
Ben-Hadj-Khalifa-Kechiche, S.
France, Reims
Hopital Robert Debre Chu de Reims
Tunisia, Monastir
Faculté de Pharmacie de Monastir
Hézard, Nathalie
France, Reims
Hopital Robert Debre Chu de Reims
France, Reims
Hémostase et Remodelage Vasculaire Post- Ischémie Hervi
Poitevin, Stephane
France, Paris
Inserm
Rémy, Marie Geneviève
France, Reims
Hopital Robert Debre Chu de Reims
Florent, Bernadette
France, Reims
Hopital Robert Debre Chu de Reims
Mahjoub, Touhami
Tunisia, Monastir
Faculté de Pharmacie de Monastir
Nguyên, Philippe H.
France, Reims
Hopital Robert Debre Chu de Reims
France, Reims
Hémostase et Remodelage Vasculaire Post- Ischémie Hervi
Statistics
Citations: 11
Authors: 7
Affiliations: 4
Identifiers
Doi:
10.1007/s11239-010-0490-4
ISSN:
09295305
e-ISSN:
1573742X