Background: Beside the oral anti-Xa agents, parenteral forms of the inhibitors of factor Xa such as otamixaban (Sanofi Aventis, Paris, France) and DX9065a (Mitsubishi Pharmaceuticals, Tokyo, Japan) have also been developed. Andexanet alfa is a broad-spectrum neutralizing agent for anti-Xa drugs.
Aims: This study is designed to compare the neutralization profile of andexanet alfa for apixaban and rivaroxaban with otamixaban and DX9065a in various laboratory assays.
Methods: Anti-Xa agents were supplemented in plasma in the concentration range of 0.0 – 1.0 ug/ml. Individual aliquots of samples were supplemented with either saline or andexanet alfa at a final concentration of 100 ug/ml. Factor Xa activity was measured by using an amidolytic method. APTT, and thrombin generation inhibition studies were also carried out. The inhibitory effects of each of these agents towards factor Xa were calculated and their reversal by andexanet alfa was determined. Results were compiled as mean SD of multiple determination.
Results: Both the oral and parenteral anti-Xa agents produced a concentration dependant inhibition of factor-Xa with the IC50 values ranging from 0.17 – 1.1 ug/ml in control group. Supplementation of andexanet alfa at 100 ug/ml resulted in the neutralization of the anti-Xa activities of these agents with the IC50 values ranging from 0.22 – 1.1 ug/ml. Andexanet alfa at 100 ug/ml effectively neutralized the anticoagulant effects of otamixaban in comparison to Apixaban and rivaroxaban.
Conclusions: Our results suggest that andexanet alfa is capable of neutralizing the effects of potent parenteral anti-Xa agents such as otamixaban. These results also underscore that the in-vitro anti-Xa potency of both the oral and parenteral anti-Xa agents does not fully reflect their inhibitory effects on the overall coagulation process. Nevertheless, andexanet alfa may be a useful agent in the neutralization of parenteral anti-Xa agents.
To cite this abstract in AMA style:Siddiqui F, Hoppensteadt D, Walenga J, Jeske W, Tafur A, Ramacciotti E, Fareed J. Neutralization of the Oral and Parenteral Anti-Xa Agents by Andexanet Alfa [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/neutralization-of-the-oral-and-parenteral-anti-xa-agents-by-andexanet-alfa/. Accessed May 16, 2022.
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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/neutralization-of-the-oral-and-parenteral-anti-xa-agents-by-andexanet-alfa/