title: Differential coagulation inhibitory effect of fondaparinux, enoxaparin and unfractionated heparin in cell models of thrombin generation.
abstract: Anticoagulants, including unfractionated heparin (UFH), enoxaparin and fondaparinux, are approved drugs in acute coronary syndrome (ACS). Monocytes and monocyte-derived microparticles (MMPs) play an important procoagulant role in ACS by expressing high tissue factor (TF) levels, which in turn triggers thrombin generation. The objective of our study is to compare the in-vitro inhibitory effect of UFH, enoxaparin and fondaparinux in monocytes and MMP models. Human-elutriated monocytes were activated for 5 and 18 h by lipopolysaccharide to obtain activated monocytes (ac-M) or MMPs, respectively. Thrombin generation inhibition was assessed using ac-M or MMPs mixed with platelet-poor plasma containing increased concentrations of anticoagulants. Thrombin generation inhibition was dose-dependent with a differential effect according to the drug: the highest for UFH, the lowest for fondaparinux. Rate index was the most sensitive parameter. For fondaparinux, its IC50 values (anti-Xa IU/ml) were 0.59±0.05 for ac-M and 0.17±0.03 for MMPs. For enoxaparin, rate index IC50 values were 0.27±0.03 for ac-M and 0.19±0.02 for MMPs. Our data support the notion that cell-induced thrombin generation assay may be a reliable alternative to anti-Xa assessment in determining patient anticoagulation level.
authors.affiliation: Unité de Recherche des Maladies Hématologiques et Auto-Immunes, Monastir, Tunisia.
authors.forename: Sonia
authors.initials: S
authors.lastname: Ben-Hadj-Khalifa
authors.forename: Nathalie
authors.initials: N
authors.lastname: Hézard
authors.forename: Wassim Y
authors.initials: WY
authors.lastname: Almawi
authors.forename: Marie G
authors.initials: MG
authors.lastname: Remy
authors.forename: Bernadette
authors.initials: B
authors.lastname: Florent
authors.forename: Touhami
authors.initials: T
authors.lastname: Mahjoub
authors.forename: Philippe
authors.initials: P
authors.lastname: Nguyen
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D055252:Cell-Derived Microparticles / Q000187:drug effects; D002478:Cells, Cultured; D017984:Enoxaparin / Q000494:pharmacology; D000077425:Fondaparinux; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D011134:Polysaccharides / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D011134:Polysaccharides; D006493:Heparin; D013917:Thrombin; D000077425:Fondaparinux