Faculté de Pharmacie, Inserm UMR-S1140, Paris, France; Sorbonne Paris Cité, Université Paris Descartes, Paris, France; Service de Cardiologie, Hôpital du Val de Grâce, Paris, France.
J Thromb Haemost. 2015 Mar;13(3):426-36. doi: 10.1111/jth.12830. Epub 2015 Feb 5.
Non-specific hemostatic agents, namely activated prothrombin complex concentrate (aPCC), PCC and recombinant activated factor (F) VII (rFVIIa), can be used, off-label, to reverse the effects of FXa inhibitors in the rare cases of severe hemorrhages, as no approved specific antidote is available. We have evaluated the ability of aPCC, PCC and rFVIIa to reverse apixaban.
Healthy volunteer whole blood was spiked with therapeutic or supra-therapeutic apixaban concentrations and two doses of aPCC, PCC or rFVIIa. Tests performed included a turbidimetry assay for fibrin polymerization kinetics analysis, scanning electron microscopy for fibrin network structure observation, thrombin generation assay (TGA), thromboelastometry, prothrombin time and activated partial thromboplastin time.
aPCC generated a dense clot constituting thin and branched fibers similar to those of a control without apixaban, increased fibrin polymerization velocity and improved quantitative (endogenous thrombin potential and peak height) as well as latency (clotting and lag times) parameters. Adding PCC also improved the fibrin and increased quantitative parameters, but fibrin polymerization kinetics and latency parameters were not corrected. Finally, rFVIIa improved latency parameters but failed to restore the fibrin network structure, fibrin polymerization velocity and quantitative parameters.
aPCC was more effective than PCC or rFVIIa in reversing in vitro the effects of apixaban. aPCC rapidly triggered the development of an apparently normal fibrin network and corrected latency and quantitative parameters, whereas PCC or rFVIIa had only a partial effect.
非特异性止血剂，即活化的凝血酶原复合物浓缩物（aPCC）、PCC 和重组活化因子（F）VII（rFVIIa），可在没有批准的特异性解毒剂的情况下，超适应证用于逆转 FXa 抑制剂在罕见严重出血情况下的作用。我们评估了 aPCC、PCC 和 rFVIIa 逆转阿哌沙班的能力。
健康志愿者全血中加入治疗或超治疗浓度的阿哌沙班和两种剂量的 aPCC、PCC 或 rFVIIa。进行的测试包括浊度法纤维蛋白聚合动力学分析、扫描电子显微镜纤维蛋白网络结构观察、凝血酶生成试验（TGA）、血栓弹力描记术、凝血酶原时间和活化部分凝血活酶时间。
aPCC 产生了致密的凝块，构成了与没有阿哌沙班的对照相似的细而分支的纤维，增加了纤维蛋白聚合速度，并改善了定量（内源性凝血酶潜能和峰高）以及潜伏期（凝血和延滞时间）参数。添加 PCC 也改善了纤维蛋白并增加了定量参数，但纤维蛋白聚合动力学和潜伏期参数未得到纠正。最后，rFVIIa 改善了潜伏期参数，但未能恢复纤维蛋白网络结构、纤维蛋白聚合速度和定量参数。
aPCC 比 PCC 或 rFVIIa 更有效地逆转阿哌沙班的体外作用。aPCC 迅速引发明显正常的纤维蛋白网络的发展，并纠正潜伏期和定量参数，而 PCC 或 rFVIIa 仅具有部分作用。
