Laboratoire d'Hématologie, Groupe de Recherche sur la Thrombose, EA 3065, Université J Monet, Inserm CIE 3, CHU Saint Etienne, 42055 Saint Etienne cedex 2, France.
Thromb Haemost. 2013 Mar;109(3):504-9. doi: 10.1160/TH12-05-0321. Epub 2013 Jan 17.
There is no in vitro data on the comparison of the effects of danaparoid, argatroban and fondaparinux on thrombin generation in patients with heparin-induced thrombocytopenia. It was the study objective to compare the in vitro anticoagulant potential of argatroban, danaparoid and fondaparinux using a thrombin generation assay TGA on a mixture of control platelet-rich plasma (PRP) and HIT patient platelet-poor plasma (PPP). The plasma of seven patients with a clear HIT diagnosed at our institution was selected. Mixtures of donor PRP and patient PPP were incubated with unfractionated heparin 0.2 U.mL⁻¹, argatroban at 600 ng.mL⁻¹, argatroban at 400 ng.mL⁻¹, danaparoid at 0.65 IU.mL⁻¹ and fondaparinux at 1 μg.mL⁻¹. Thrombin generation was assessed by calibrated thrombinography. The percentage of inhibition of the endogenous thrombin potential observed with argatroban at 600 ng.mL⁻¹ was statistically significantly higher compared with those observed with fondaparinux (median: 53.6% vs. 3.9%; p=0.031) but not compared with argatroban at 400 ng.mL⁻¹ and danaparoid. The percentage of inhibition of the thrombin peak observed with argatroban at 600 ng.mL⁻¹ was statistically significantly higher compared with those observed with danaparoid (median: 71.2 vs. 56.8; p=0.031) and fondaparinux (mean: 71.2 vs. 30; p=0.031) but not with argatroban at 400 ng.mL⁻¹. In conclusion, the in vitro effect of argatroban and danaparoid on thrombin generation seems to corroborate the results of clinical studies of these drugs in the treatment of HIT in term of efficiency. Fondaparinux showed a very small effect on thrombin generation evaluated by calibrated thrombinography.
目前尚无关于达那肝素、阿加曲班和磺达肝癸钠在体外对肝素诱导的血小板减少症患者凝血酶生成影响的比较数据。本研究旨在通过凝血酶生成试验（TGA）比较阿加曲班、达那肝素和磺达肝癸钠在混合正常血小板富血浆（PRP）和肝素诱导的血小板减少症（HIT）患者血小板贫血浆（PPP）中的体外抗凝潜力。选择了我院明确诊断的 7 例 HIT 患者的血浆。将供体 PRP 和患者 PPP 的混合物与未分级肝素 0.2 U/ml 孵育，分别加入阿加曲班 600ng/ml、阿加曲班 400ng/ml、达那肝素 0.65IU/ml 和磺达肝癸钠 1μg/ml。通过校准的凝血酶谱评估凝血酶生成。阿加曲班 600ng/ml 观察到的内源性凝血酶潜能抑制率与磺达肝癸钠（中位数：53.6%比 3.9%；p=0.031）相比具有统计学显著差异，但与阿加曲班 400ng/ml 和达那肝素相比则无差异。阿加曲班 600ng/ml 观察到的凝血酶峰抑制率与达那肝素（中位数：71.2%比 56.8%；p=0.031）和磺达肝癸钠（平均：71.2%比 30%；p=0.031）相比具有统计学显著差异，但与阿加曲班 400ng/ml 相比则无差异。结论，阿加曲班和达那肝素对凝血酶生成的体外作用似乎与这些药物治疗 HIT 的临床研究结果一致，即在疗效方面。磺达肝癸钠在通过校准的凝血酶谱评估的凝血酶生成中显示出非常小的作用。
