A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa

@article{Lu2013ASA,
  title={A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa},
  author={Genmin Lu and Francis R Deguzman and Stanley J. Hollenbach and Mark J. Karbarz and Keith Abe and Gail Lee and Peng Luan and Athiwat Hutchaleelaha and Mayuko Inagaki and Pamela B. Conley and David R. Phillips and Uma Sinha},
  journal={Nature Medicine},
  year={2013},
  volume={19},
  pages={446-451}
}
Inhibitors of coagulation factor Xa (fXa) have emerged as a new class of antithrombotics but lack effective antidotes for patients experiencing serious bleeding. We designed and expressed a modified form of fXa as an antidote for fXa inhibitors. This recombinant protein (r-Antidote, PRT064445) is catalytically inactive and lacks the membrane-binding γ-carboxyglutamic acid domain of native fXa but retains the ability of native fXa to bind direct fXa inhibitors as well as low molecular weight… 
A rapid pro-hemostatic approach to overcome direct oral anticoagulants
TLDR
It is shown that a variant coagulation factor, FXaI16L, rapidly restores hemostasis in the presence of the anticoagulant effects of these inhibitors, and is more potent than a noncatalytic antidote that is currently in clinical development.
Andexanet alfa to reverse the anticoagulant activity of factor Xa inhibitors: a review of design, development and potential place in therapy
TLDR
Andexanet alfa was shown to reverse FXa inhibitors anticoagulant activity both in thrombosis animal models, healthy volunteers and patients with acute major bleeding.
Reversal of Factor Xa Inhibitors by Andexanet Alfa May Increase Thrombogenesis Compared to Pretreatment Values
  • Fakiha Siddiqui, A. Tafur, J. Fareed
  • Biology
    Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
  • 2019
TLDR
Recombinant coagulation factor Xa, inactivated Zh-zo, also known as andexanet alfa, is a modified version of human FXa that has been developed to neutralize FXa inhibitors but overshoots thrombogenesis in both the saline and FXa inhibitor supplemented systems.
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TLDR
An overview of the current state of nonspecific and specific reversal agents for the direct factor Xa inhibitors is provided, focusing on the biochemistry and mechanism of action and the preclinical assessment of newly emerging therapies.
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Andexanet alfa is a FXa decoy designed to reverse all anticoagulants that act through this part of the coagulation cascade including anti-FXa DOACs, and indirect FXa inhibitors such as low-molecular-weight heparins.
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TLDR
Evaluated in vitro the effectivity of inactive ATs to reverse anticoagulation by heparin derivatives and to compare them with non-specific fondaparinux reversal agents, like recombinant-activated factor VII (rFVIIa) or activated prothrombin-complex concentrate (aPCC), in a throm bin-generation assay (TGA).
FXa-α2-Macroglobulin Complex Neutralizes Direct Oral Anticoagulants Targeting FXa In Vitro and In Vivo.
TLDR
GDFXa-α2M is an attractive candidate for xaban neutralization neither pro- nor anticoagulant in vitro as well as in vivo and did not increase D-dimer or thrombin-antithrombin complex formation, suggesting a lack of pro-thrombotic potential.
Andexanet alfa for the reversal of anticoagulant activity in patients treated with direct and indirect factor Xa inhibitors
TLDR
Andexanet alfa shows promise to become a highly effective, novel antidote for factor Xa anticoagulation, and its biochemical profile and mechanism of action are immediately more attractive than other drugs on the market and under development due to its inert nature within the normal coagulation cascade.
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