• A-C Martin, I Gouin-Thibault, V Siguret, A Mordohay, C-M Samama, P Gaussem, B Le Bonniec, and A Godier.
• 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 1; 13 (3): 426-36.

BackgroundNon-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.MethodsHealthy 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.ResultsaPCC 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.ConclusionaPCC 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.© 2015 International Society on Thrombosis and Haemostasis.

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