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Critical Care

, 19:P348 | Cite as

Four-factor prothrombin complex concentrate (Beriplex® P/N) mediated reversal of apixaban-induced bleeding in a rabbit model

  • E Herzog
  • F Kaspereit
  • W Krege
  • J Mueller-Cohrs
  • B Doerr
  • P Niebl
  • G Dickneite
Open Access
Poster presentation

Keywords

Thrombin Rabbit Model Apixaban Thrombin Generation Coagulation Parameter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Introduction

This study assessed whether a four-factor prothrombin complex concentrate (4F-PCC; Beriplex®/Kcentra®; CSL Behring) can effectively reverse bleeding associated with the direct oral factor Xa inhibitor apixaban in an established in vivo rabbit model [1, 2].

Methods

For dose-finding purposes, anesthetized rabbits were treated with a single intravenous dose of apixaban (800 to 1,600 μg/kg). In a subsequent study phase, anesthetized rabbits were treated with apixaban (1,200 μg/kg) followed by 4F-PCC (6.25 to 100 IU/kg). Bleeding signals were quantified following a standardized kidney incision by measurement of the volume of blood loss and time to hemostasis over an observation period of 30 minutes. Blood samples were collected for monitoring of coagulation parameters.

Results

Dose-dependent increases in time to hemostasis and total blood loss were observed post apixaban administration with maximum bleeding signals seen at 1,200 μg/kg. Treatment with 4F-PCC resulted in a statistically significant reversal in apixaban-induced bleeding time (all doses) and volume (doses ≥12.5 IU/kg). Of the coagulation parameters measured, thrombin generation initiated using phospholipids only was the in vitro coagulation parameter most sensitive to 4F-PCC-mediated bleeding reversal, although statistically significant 4F-PCC-mediated reductions in the prothrombin time and whole blood clotting time were also observed.

Conclusion

In conclusion, 4F-PCC treatment effectively decreased apixaban-induced hemorrhage at a clinically relevant dose range.

References

  1. 1.
    Herzog , et al: Anesthesiology. 2014, ForthcomingGoogle Scholar
  2. 2.
    Pragst , et al: J Thromb Haemost. 2012, 10 (9): 1841-8. 10.1111/j.1538-7836.2012.04859.x.CrossRefPubMedGoogle Scholar

Copyright information

© Herzog et al.; licensee BioMed Central Ltd. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors and Affiliations

  • E Herzog
    • 1
  • F Kaspereit
    • 1
  • W Krege
    • 1
  • J Mueller-Cohrs
    • 1
  • B Doerr
    • 1
  • P Niebl
    • 1
  • G Dickneite
    • 1
  1. 1.CSL Behring GmbHMarburgGermany

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