Gerotziafas Grigoris T, Depasse François, Chakroun Tahar, Van Dreden Patrick, Samama Meyer M, Elalamy Ismail
Service d'Hématologie Biologique, Hôpital Hôtel-Dieu de Paris, LCL, Ivry sur Seine and Serbio Laboratories, Genevilliers, France.
Blood Coagul Fibrinolysis. 2004 Mar;15(2):149-56. doi: 10.1097/00001721-200403000-00006.
Fondaparinux, a selective antithrombin-dependent inhibitor of activated factor X (FXa), is effective in the prevention and treatment of deep vein thrombosis and seems to be superior to enoxaparin. However, the exact mechanism of fondaparinux antithrombotic action is still unclear. We compared the effect of clinically relevant concentrations of fondaparinux and enoxaparin on the initiation and propagation phase of prothrombin activation and on the endogenous thrombin potential (ETP). Coagulation was triggered either in whole blood or in platelet-rich plasma (PRP) by recalcification in the presence of diluted thromboplastin. Prothrombin activation in whole blood was assessed with an original method by measuring the kinetics of prothrombin F1+2 formation using an enzyme-linked immunosorbent assay. We also assessed the maximum concentration of thrombin (Cmax) and the ETP in PRP using the Thrombogram-Thrombinoscope assay. Concentrations of fondaparinux achieved in prophylaxis (0.11-0.28 anti-FXa IU/ml) prolonged the initiation phase and reduced the velocity of the propagation phase of F1+2 formation. Concentrations of enoxaparin achieved in prophylaxis (0.1-0.25 anti-FXa IU/ml) did not significantly modify these parameters. Concentrations of fondaparinux equal to or higher than 0.57 anti-FXa IU/ml significantly reduced the Cmax of F1+2 or thrombin as well as the ETP. At fondaparinux concentrations equal to or higher than 0.91 anti-FXa IU/ml, a maximum 60% inhibition of thrombin generation was observed. In the presence of enoxaparin concentrations equal to or higher than 0.8 anti-FXa IU/ml, the inhibition of thrombin generation was higher than 80%. Fondaparinux prolonged the initiation phase, decreased the velocity of the propagation phase of thrombin generation and partially reduced the total amount of generated thrombin. The inhibitory effect of fondaparinux on the initiation and propagation phase of thrombin generation seems to be responsible for its antithrombotic action. The more profound inhibition of thrombin generation induced by enoxaparin is due to its supplementary anti-activated factor II activity.
磺达肝癸钠是一种对活化因子X（FXa）具有选择性的抗凝血酶依赖性抑制剂，在预防和治疗深静脉血栓形成方面有效，且似乎优于依诺肝素。然而，磺达肝癸钠抗血栓作用的确切机制仍不清楚。我们比较了临床相关浓度的磺达肝癸钠和依诺肝素对凝血酶原激活起始阶段和传播阶段以及内源性凝血酶潜力（ETP）的影响。在稀释的凝血活酶存在下通过重新钙化在全血或富血小板血浆（PRP）中触发凝血。通过使用酶联免疫吸附测定法测量凝血酶原F1+2形成的动力学，用一种原始方法评估全血中的凝血酶原激活。我们还使用血栓图-凝血酶监测仪测定法评估PRP中凝血酶的最大浓度（Cmax）和ETP。预防中达到的磺达肝癸钠浓度（0.11-0.28抗FXa国际单位/毫升）延长了起始阶段并降低了F1+2形成传播阶段的速度。预防中达到的依诺肝素浓度（0.1-0.25抗FXa国际单位/毫升）并未显著改变这些参数。等于或高于0.57抗FXa国际单位/毫升的磺达肝癸钠浓度显著降低了F1+2或凝血酶的Cmax以及ETP。在磺达肝癸钠浓度等于或高于0.91抗FXa国际单位/毫升时，观察到凝血酶生成的最大抑制率为60%。在依诺肝素浓度等于或高于0.8抗FXa国际单位/毫升时，凝血酶生成的抑制率高于80%。磺达肝癸钠延长了起始阶段，降低了凝血酶生成传播阶段的速度，并部分降低了生成的凝血酶总量。磺达肝癸钠对凝血酶生成起始阶段和传播阶段的抑制作用似乎是其抗血栓作用的原因。依诺肝素诱导的对凝血酶生成的更深刻抑制是由于其额外的抗活化因子II活性。
