PMID- 21577096 OWN - NLM STAT- MEDLINE DCOM- 20111223 LR - 20181201 IS - 1473-5733 (Electronic) IS - 0957-5235 (Linking) VI - 22 IP - 5 DP - 2011 Jul TI - Differential coagulation inhibitory effect of fondaparinux, enoxaparin and unfractionated heparin in cell models of thrombin generation. PG - 369-73 LID - 10.1097/MBC.0b013e328344f7d0 [doi] AB - 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. FAU - Ben-Hadj-Khalifa, Sonia AU - Ben-Hadj-Khalifa S AD - Unite de Recherche des Maladies Hematologiques et Auto-Immunes, Monastir, Tunisia. FAU - Hezard, Nathalie AU - Hezard N FAU - Almawi, Wassim Y AU - Almawi WY FAU - Remy, Marie G AU - Remy MG FAU - Florent, Bernadette AU - Florent B FAU - Mahjoub, Touhami AU - Mahjoub T FAU - Nguyen, Philippe AU - Nguyen P LA - eng PT - Comparative Study PT - Journal Article PL - England TA - Blood Coagul Fibrinolysis JT - Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis JID - 9102551 RN - 0 (Anticoagulants) RN - 0 (Enoxaparin) RN - 0 (Polysaccharides) RN - 9005-49-6 (Heparin) RN - EC 3.4.21.5 (Thrombin) RN - J177FOW5JL (Fondaparinux) SB - IM MH - Anticoagulants/*pharmacology MH - Blood Coagulation/*drug effects MH - Cell-Derived Microparticles/drug effects MH - Cells, Cultured MH - Enoxaparin/pharmacology MH - Fondaparinux MH - Heparin/pharmacology MH - Humans MH - Inhibitory Concentration 50 MH - Models, Biological MH - Monocytes/cytology/*drug effects MH - Polysaccharides/pharmacology MH - Thrombin/*antagonists & inhibitors/biosynthesis EDAT- 2011/05/18 06:00 MHDA- 2011/12/24 06:00 CRDT- 2011/05/18 06:00 PHST- 2011/05/18 06:00 [entrez] PHST- 2011/05/18 06:00 [pubmed] PHST- 2011/12/24 06:00 [medline] AID - 10.1097/MBC.0b013e328344f7d0 [doi] PST - ppublish SO - Blood Coagul Fibrinolysis. 2011 Jul;22(5):369-73. doi: 10.1097/MBC.0b013e328344f7d0.