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Multimodal assessment of non‐specific hemostatic agents for apixaban reversal
Author(s) -
Martin A.C.,
GouinThibault I.,
Siguret V.,
Mordohay A.,
Samama C.M.,
Gaussem P.,
Le Bonniec B.,
Godier A.
Publication year - 2015
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.12830
Subject(s) - fibrin , thromboelastometry , apixaban , partial thromboplastin time , clotting time , thrombin , medicine , fibrinogen , thromboplastin , coagulation , chemistry , pharmacology , anesthesia , platelet , immunology , rivaroxaban , atrial fibrillation , warfarin
Summary Background Non‐specific hemostatic agents, namely activated prothrombin complex concentrate ( aPCC ), PCC and recombinant activated factor (F) VII ( rFVII a), can be used, off‐label, to reverse the effects of FX a inhibitors in the rare cases of severe hemorrhages, as no approved specific antidote is available. We have evaluated the ability of aPCC , PCC and rFVII a to reverse apixaban. Methods Healthy volunteer whole blood was spiked with therapeutic or supra‐therapeutic apixaban concentrations and two doses of aPCC , PCC or rFVII a. 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. Results 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, rFVII a improved latency parameters but failed to restore the fibrin network structure, fibrin polymerization velocity and quantitative parameters. Conclusion aPCC was more effective than PCC or rFVII a 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 rFVII a had only a partial effect.