DOAC-Stop™ reverses the anticoagulant effect of asundexian and milvexian.
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BACKGROUND: Asundexian and milvexian are small molecule factor (F) XIa inhibitors, whereas abelacimab is an antibody that binds FXI and blocks its activation and activity. All three FXI inhibitors are currently undergoing Phase 3 evaluation. Like heparin and dabigatran, asundexian, milvexian, and abelacimab prolong the activated partial thromboplastin time (APTT) in a concentration-dependent manner. DOAC-Stop™ (DS) is an activated charcoal-based compound that adsorbs direct oral anticoagulants such as dabigatran, but not heparin, from plasma. It is unknown whether DS also neutralizes asundexian and milvexian. OBJECTIVE: To determine whether DS reverses the prolongation of the APTT caused by asundexian or milvexian. Dabigatran was used as a positive control, while abelacimab and heparin served as negative controls. METHODS: The APTT in human plasma, with or without asundexian, milvexian, abelacimab, dabigatran, or heparin, was determined before and after DS treatment. RESULTS: As expected, all drugs produced concentration-dependent prolongation of the APTT. DS returned the APTT to baseline values with asundexian, milvexian, and dabigatran, but not with abelacimab or heparin. The APTT was prolonged in a more than additive manner with the combination of 2.5 μM milvexian and 0.125 U/mL heparin. However, DS only reversed the APTT prolongation induced by milvexian, but not that by heparin. CONCLUSION: DS reverses the effect of asundexian and milvexian on the APTT and distinguishes between the APTT effects of milvexian and heparin.
