Interferences Associated with the Factor XIa Inhibitors Asundexian and Milvexian in Routine and Specialised Coagulation Assays and their Removal by Activated Charcoal-Based Adsorbents.

Background: Direct inhibition of factor XI/XIa (FXI/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 characterised.

Objective: This study evaluated the interferences associated with the FXIa inhibitors asundexian and milvexian in a of panel routine and specialised 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 ng/mL - 10,000 ng/mL) and assayed for routine and specialised coagulation parameters, before and after treatment with charcoal-based adsorbents, using Sysmex CN/CS-series analysers. 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 APTT-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.

Conclusions: Emerging FXIa inhibitors interfere significantly with FXIa-dependent coagulation assays, potentially leading to misinterpretation of haemostatic function. However, charcoal-based adsorbents efficiently remove these interferences and enable routine and specialised coagulation testing in the presence of asundexian and milvexian.