BACKGROUND: Medical devices, such as central venous catheters and mechanical heart valves (MHVs), are associated with an increased risk of thrombosis. Clotting on these devices is initiated by contact with the system surface. Adsorbed factor (F)XII undergoes autoactivation and activates FXI, which then propagates coagulation. Abelacimab, asundexian, and milvexian are FXI or FXIa inhibitors currently undergoing or having completed phase 3 evaluation.
OBJECTIVES: To compare the effects of abelacimab, asundexian, and milvexian on activated partial thromboplastin time (APTT), catheter-induced clotting, and device-induced thrombin generation.
METHODS: The effects of abelacimab, asundexian, and milvexian on APTT (measured with HemosIL APTT-SP reagent), catheter-induced clotting, and thrombin generation induced by catheter segments or MHV leaflets were assessed in human platelet-poor plasma. Thrombin generation was monitored over time using a fluorogenic substrate, and peak thrombin and endogenous thrombin potential were quantified.
RESULTS: Abelacimab, asundexian, and milvexian prolonged APTT and catheter-induced clotting time and attenuated device-induced thrombin generation in a concentration-dependent manner. At clinically relevant concentrations, abelacimab and milvexian had more pronounced effects on APTT, catheter-induced clotting, and device-induced thrombin generation than asundexian. Even at the highest concentration tested, asundexian showed less inhibition of device-induced thrombin generation than the other inhibitors.
CONCLUSION: At the concentrations achieved by the dosing regimens evaluated in the phase 3 trials, abelacimab and milvexian had greater effects on APTT, catheter-induced clotting, and thrombin generation induced by catheters or MHVs than asundexian.
