DOAC-Stop reverses the anticoagulant effect of asundexian and milvexian.
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abstract
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 3 FXI inhibitors are currently undergoing phase 3 evaluation. Similar to 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: This study aimed 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 reversed only 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.
