Reversal of Rivaroxaban and Dabigatran by Prothrombin Complex Concentrate: A Randomized, Placebo-Controlled, Crossover Study in Healthy Subjects

@article{Eerenberg2011ReversalOR,
  title={Reversal of Rivaroxaban and Dabigatran by Prothrombin Complex Concentrate: A Randomized, Placebo-Controlled, Crossover Study in Healthy Subjects},
  author={Elise S. Eerenberg and Pieter Willem Kamphuisen and Meertien K. Sijpkens and Joost C. M. Meijers and Harry R. Buller and Marcel Levi},
  journal={Circulation},
  year={2011},
  volume={124},
  pages={1573–1579}
}
Background— Rivaroxaban and dabigatran are new oral anticoagulants that specifically inhibit factor Xa and thrombin, respectively. Clinical studies on the prevention and treatment of venous and arterial thromboembolism show promising results. A major disadvantage of these anticoagulants is the absence of an antidote in case of serious bleeding or when an emergency intervention needs immediate correction of coagulation. This study evaluated the potential of prothrombin complex concentrate (PCC… 
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TLDR
Some non-specific reversal agents appear to be able to reverse the anticoagulant activity of rivaroxaban or dabigatran, however, clinical evaluation is needed regarding haemorrhagic situations, and a meticulous risk-benefit evaluation regarding their use in this context is required.
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TLDR
Blood loss following trauma in dabigatran-anticoagulated pigs was successfully reduced by 50 U/kg aPCC, as measured by several parameters including EXTEM clotting time (CT) and PT.
Thrombotic safety of prothrombin complex concentrate (Beriplex P/N) for dabigatran reversal in a rabbit model.
Evaluation of Prothrombin Complex Concentrate and Recombinant Activated Factor VII to Reverse Rivaroxaban in a Rabbit Model
TLDR
RFVIIa and PCC partially improved laboratory parameters, but did not reverse rivaroxaban induced-bleeding and safety, respectively.
More efficient reversal of dabigatran inhibition of coagulation by activated prothrombin complex concentrate or recombinant factor VIIa than by four-factor prothrombin complex concentrate.
Prothrombin Complex Concentrate Is Effective in Treating the Anticoagulant Effects of Dabigatran in a Porcine Polytrauma Model
TLDR
Four-factor PCC (50 or 100 U/kg) is effective in reducing blood loss in dabigatran-anticoagulated pigs, but higher doses may induce a procoagulant state.
Reversal of novel oral anticoagulants in patients with major bleeding
TLDR
Target-specific antidotes are in development and hold promise for NOAC reversal, but require further investigation, and Administration of PCC or aPCC may be considered in addition to supportive measures for patients with severe or life-threatening bleeding.
Edoxaban Effects on Bleeding Following Punch Biopsy and Reversal by a 4-Factor Prothrombin Complex Concentrate
TLDR
The 4F-PCC dose-dependently reversed the effects of edoxaban (60 mg), with complete reversal of bleeding duration and endogenous thrombin potential and partial reversal of prothrombin time following 50 IU/kg.
Prothrombin complex concentrates and a specific antidote to dabigatran are effective ex-vivo in reversing the effects of dabigatran in an anticoagulation/liver trauma experimental model
TLDR
PCC and aPCC were effective in reducing the anticoagulant effects of dabIGatran under different conditions, while aDabi-Fab fully corrected all coagulation measures and decreased the plasma concentration of dabigatran below the limit of detection.
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Reversal of Rivaroxaban and Dabigatran by Prothrombin Complex Concentrate : A Randomized , Placebo-Controlled , Crossover Study in Healthy Subjects ”
Eerenberg et al 1 recently published a very interesting article on the reversal of rivaroxaban and dabigatran anticoagulation by prothrom-bin complex concentrate (PCC). In their study, the authors…
Evaluation of Prothrombin Complex Concentrate and Recombinant Activated Factor VII to Reverse Rivaroxaban in a Rabbit Model
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