Interferences associated with the factor XIa inhibitors asundexian and milvexian in routine and specialized coagulation assays and their removal by activated charcoal-based adsorbents

BACKGROUND: Direct inhibition of factor (F)XI/FXIa is emerging as a promising anticoagulant strategy to mitigate the risk of bleeding typically associated with antithrombotic medications, including direct oral anticoagulants (DOACs). While DOACs are known to interfere with a broad range of coagulation assays, the interferences associated with emerging FXIa inhibitors remain incompletely characterized. OBJECTIVES: This study evaluated the interferences associated with the FXIa inhibitors asundexian and milvexian in a panel of routine and specialized coagulation assays. Additionally, we assessed the capacity of charcoal-based adsorbents-including raw activated charcoal and DOAC-Stop-to remove interferences in coagulometric assays. METHODS: Human-derived plasma was anticoagulated with increasing concentrations of asundexian or milvexian (0-10 000 ng/mL) and assayed for routine and specialized coagulation parameters before and after treatment with charcoal-based adsorbents using Sysmex CN/CS-series analyzers. Plasma was anticoagulated with both asundexian and milvexian at therapeutic and supratherapeutic concentrations representative of those reported in recent pharmacokinetic trials. RESULTS: Asundexian and milvexian produced significant dose-dependent interferences in FXIa-dependent coagulation assays, including markedly prolonged activated partial thromboplastin time-based clotting times and markedly reduced intrinsic coagulation factor activities. Treatment with charcoal-based adsorbents effectively removed both asundexian- and milvexian-associated interferences across all affected assays. CONCLUSION: Emerging FXIa inhibitors interfere significantly with FXIa-dependent coagulation assays, potentially leading to misinterpretation of hemostatic function. However, charcoal-based adsorbents efficiently remove these interferences and enable routine and specialized coagulation testing in the presence of asundexian and milvexian.