Abstract Number: PB1009
Meeting: ISTH 2022 Congress
Background: Milvexian is a small molecule FXIa inhibitor currently in Phase II clinical trials with the potential for reduced bleeding risk compared to currently approved direct oral anticoagulants (DOACs). Patients taking milvexian may require anticoagulation with heparin (UFH, LMWH) or bivalirudin for medical procedures such as percutaneous coronary intervention (PCI) or cardiopulmonary bypass (CPB) surgery. However, it is currently unknown what effect milvexian will have when combined with heparin or bivalirudin. Activated clotting time (ACT) is the standard whole-blood coagulation assay used perioperatively to monitor anticoagulation levels for procedures such as PCI or CPB.
Aims: Assess impact of milvexian when added to UFH, enoxaparin (LMWH), or bivalirudin in ACT assay.
Methods: Milvexian (0.1 – 6 μM) was added to freshly drawn citrated whole blood obtained from healthy human donors either alone or combined with UFH (0.5 or 1 U/mL), enoxaparin (2 or 4 U/mL), or bivalirudin (12.5 μg/mL). ACT clotting times were measured on ACT Plus automated coagulation timers using High-Range ACT (HR-ACT) cartridges (Medtronic USA).
Results: 0.5 and 1 U/mL of UFH prolonged ACT by 1.3- and 1.6-fold, 2 and 4 U/mL enoxaparin prolonged ACT by 1.3 and 1.5-fold, and 12.5 μg/mL bivalirudin prolonged ACT by 2.45-fold. Milvexian alone demonstrated a modest effect on HR-ACT clotting times, with a maximal prolongation of 1.45-fold at 6 μM. Combining milvexian with either UFH (1 U/mL) or enoxaparin (4 U/mL) potentiated the maximum ACT prolongation (4.0- and 4.28-fold, respectively), whereas combining milvexian with bivalirudin had no effect compared to milvexian alone (1.55-fold vs. 1.45-fold, respectively).
Conclusion(s): Milvexian demonstrates a synergistic effect with UFH and enoxaparin, but not bivalirudin, in vitro in ACT assays. A clinical study may be required to confirm whether this synergy occurs in subjects taking milvexian and the potential implications if any in patients is unknown at this time.
To cite this abstract in AMA style:Bunce M, Chintala M. Synergistic Effect of the Factor XIa Inhibitor Milvexian with Heparin But Not Bivalirudin in Activated Clotting Time Assays in Human Whole Blood In Vitro [abstract]. https://abstracts.isth.org/abstract/synergistic-effect-of-the-factor-xia-inhibitor-milvexian-with-heparin-but-not-bivalirudin-in-activated-clotting-time-assays-in-human-whole-blood-in-vitro/. Accessed September 22, 2023.
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