PB0550 - Differential Neutralization of Unfractionated Heparin and Enoxaparin by Andexanet Alfa

Background: Andexanet alfa is a clinically used antidote for the neutralization of the bleeding effects of Direct Oral Anticoagulant (Direct Xa) agents such as Rivaroxaban and Apixaban. It is a molecularly modified factor Xa decoy protein with high specificity for factor Xa inhibitors. Unfractionated heparin (UFH) and low molecular weight heparins (LMWHs) exhibit both anti-Xa and anti-IIa activities.

Aims: The purpose of this study is to investigate the relative neutralization of the anticoagulant effects of UFH and enoxaparin by andexanet alfa in whole blood assays such as activated clotting time (ACT) and thrombelastography (TEG).

Methods: The neutralization profiles of UFH and enoxaparin were studied by andexanet alfa at various concentrations. The final concentration of UFH used for activated clotting time (ACT) was 10 μg/ml, and for enoxaparin was 25 μg/ml. Andexanet alfa was used in a concentration range of 6.25-200 μg/ml. For the thromboelastography (TEG) analysis the concentration of all drugs were proportionately reduced by a factor of ten. The results were analyzed using R open source statistical software.

Results: Andexanet alfa at 200 μg/ml moderately neutralized UFH at the concentrations tested in ACT. The ANOVA test yielded a significant result when comparing the means of UFH treated at various andexanet alfa concentrations. The Tukey Post-Hoc test revealed significant differences between the UFH and UFH treated with andexanet alfa at all concentrations tested except at 6.25 μg/ml. Andexanet alfa did not effectively neutralize enoxaparin. There was no concentration dependent change in the neutralization profiles of UFH and enoxaparin at a concentration range of 12.5 μg/ml - 200 μg/ml. In the TEG assays, andexanet alfa at 10 μg/ml partially neutralized the anticoagulant effects of UFH at 1 ug/ml.

Conclusion(s): These studies indicate that andexanet alfa may be useful in neutralization of UFH and warrants in-vivo validation.