Low concentrations of recombinant activated factor VII normalize coagulation patterns by reversing the changes in viscoelastic testing parameters induced by abelacimab in vitro

Background

Low doses of recombinant activated factor (F)VII (rFVIIa), used to manage bleeding in patients with severe FXI deficiency, have been proposed to bypass effects of the FXI/FXIa inhibitor abelacimab.

Objectives

To test whether low concentrations of rFVIIa could abolish changes in coagulation parameters induced by abelacimab as measured by rotational thromboelastometry.

Methods

Whole blood specimens obtained in citrated tubes from 6 healthy donors were incubated with 15 and 30 μg/mL of abelacimab or vehicle for 10 minutes at 37 °C. Specimens were subsequently spiked with rFVIIa at 0.5 and 1 μg/mL or vehicle. Clot formation was monitored using rotational thromboelastometry delta analyzers and the nonactivated thromboelastometry test. Clotting time (CT, in seconds), clot formation time (CFT, in seconds), α angle, etc. were measured and compared with vehicle (excipient solution containing His/His-HCl, sucrose, polysorbate 20 solution) and reference ranges provided by the manufacturer.

Results

Abelacimab at 15 and 30 μg/mL concentrations increased CT by 61% and 64%, CFT by 37% and 32%, and decreased α angle by 10% and 14% compared with baseline, respectively. Adding rFVIIa at 0.5 and 1.0 μg/mL shortened CT by 21% and 38%, CFT by 33% and 49%, and increased α angle by 29% and 47%, respectively. Nonactivated thromboelastometry parameters generally remained within normal reference ranges when rFVIIa was added.

Conclusion

Low concentrations of rFVIIa (0.5-1 μg/mL) corrected the effects of abelacimab as assessed by rotational thromboelastometry. Our data support using low doses of rFVIIa for bleeding management in patients treated with abelacimab.