Abstract 14187: Differential Neutralization of Unfractionated and Low Molecular Weight Heparin by Andexanet Alfa

Abstract

Introduction: Andexanet Alfa is an antidote for the neutralization of the bleeding effects of Direct Oral Anticoagulant (Direct Xa) agents such as Rivaroxaban and Apixaban. It represents 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. The purpose of this study is to investigate the relative neutralization of the anti-coagulant effects UFH and enoxaparin by andexanet alfa in whole blood assays such as activated clotting time (ACT) and thromelastography (TEG). Methods: The neutralization profiles of UFH and enoxaparin were studied by Andexanet 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 was used in a concentration range of 12.5 ug/ml. For the thromboelastographic (TEG) analysis the concentration of all drugs were proportionately reduced. The results were analyzed using R open source statistical software. In order to compare the means of the groups, analysis of variance (ANOVA) tests were performed. If the ANOVA test yielded a significant result, a Tukey post-hoc analysis was performed. A pearson correlation was run for each parameter with respect to the dose of the drug. Results: Andexanet at 200 ug/ml moderately neutralized UFH (302 s vs 198). Andexanet minimally neutralized enoxaparin (200 s vs 190 s). There was no concentration dependent change in the neutralization profiles of UFH and enoxaparin at a concentration range of 12.5 ug/ml - 200 ug/ml. In the TEG assays, Andexanet alfa at 10 ug/ml partially neutralized the anticoagulant effects of UFH at 1 ug/ml as measured by various TEG parameters. At 20 ug/ml, stronger inhibition of all parameters were noted. Discussion: These studies suggest that Andexanet Alfa may be an effective neutralizing agent for UFH, however, it is ineffective in neutralizing LMWH at the concentrations studied. It is interesting to note that LMWHs have a higher anti-Xa to IIa ratio in comparison to heparin, however, their neutralization is lesser with Andexanet. These studies suggest that andexanet can be used in combination with protamine sulfate to neutralize UFH.