Ben-Hadj-Khalifa Sonia, Hézard Nathalie, Almawi Wassim Y, Remy Marie G, Florent Bernadette, Mahjoub Touhami, Nguyen Philippe
Unité de Recherche des Maladies Hématologiques et Auto-Immunes, Monastir, Tunisia.
Blood Coagul Fibrinolysis. 2011 Jul;22(5):369-73. doi: 10.1097/MBC.0b013e328344f7d0.
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.
包括普通肝素（UFH）、依诺肝素和磺达肝癸钠在内的抗凝剂是急性冠状动脉综合征（ACS）的获批药物。单核细胞和单核细胞衍生的微粒（MMPs）通过表达高水平的组织因子（TF）在ACS中发挥重要的促凝作用，进而触发凝血酶生成。我们研究的目的是比较UFH、依诺肝素和磺达肝癸钠在单核细胞和MMP模型中的体外抑制作用。通过脂多糖将人淘洗单核细胞分别激活5小时和18小时，以分别获得活化单核细胞（ac-M）或MMPs。使用与含有浓度递增抗凝剂的乏血小板血浆混合的ac-M或MMPs评估凝血酶生成抑制情况。凝血酶生成抑制呈剂量依赖性，且不同药物有不同效果：UFH的抑制作用最强，磺达肝癸钠的抑制作用最弱。速率指数是最敏感的参数。对于磺达肝癸钠，其IC50值（抗Xa国际单位/毫升）对于ac-M为0.59±0.05，对于MMPs为0.17±0.03。对于依诺肝素，速率指数IC50值对于ac-M为0.27±0.03，对于MMPs为0.19±0.02。我们的数据支持这样一种观点，即在确定患者抗凝水平时，细胞诱导的凝血酶生成测定可能是抗Xa评估的可靠替代方法。
