PB0548 - Abelacimab, a Factor XI/XIa Antibody Inhibits Clotting in Hemodialysis Circuits Ex Vivo

Background: Effective anticoagulants are needed to avoid blood clotting during extracorporeal circulation. Alternative to conventionally used heparins could be drugs targeting factor XI (FXI)/activated FXI (FXIa) such as the novel monoclonal antibody abelacimab.

Aims: We compared the effects of abelacimab used in combination with enoxaparin to enoxaparin alone.

Methods: Whole blood was collected from 10 healthy volunteers in two bags containing either 1.2mg enoxaparin alone (control group) or 1.2mg enoxaparin plus 5mg abelacimab (treatment group). Each bag was attached to a hemodialysis device, and blood was circulated for a maximum of 3 hours or until the device stopped due to clotting, as assessed by a sudden rise in transmembrane pressure. We measured coagulation parameters, performed whole blood aggregation and thromboelastometry at baseline, 15min, 30min, 1h, 2h and 3h after circuit initiation. The primary endpoint was time to filter clotting.

Results: 8 male and 2 female (mean age: 37±7 years) volunteers were included. Abelacimab in combination with enoxaparin significantly prolonged the time to circuit clotting from a median of 120min (IQR:97-147) to 180min (IQR:180-180) (p < 0.001) and decreased the transmembrane pressure from 66mmHg to 13mmHg at the end of the circuit flow (p=0.042). Furthermore, it preserved median fibrinogen levels (207mg/dl vs. 178mg/dl) (p=0.038) and median platelets counts (135x109/L vs 106x109/L) (p=0.002), improved ristocetin (22U vs. 2U) (p=0.015); thrombin receptor activating peptide (29U vs. 19U) (p=0.015) and arachidonic acid (23U vs. 17U) (p=0.001) induced platelet aggregation; and prolonged clotting times in thromboelastometry (INTEM (p < 0.001) and HEPTEM (p=0.003) at the end of the experiments.

Conclusion(s): In an ex vivo model of hemodialysis that is aggressive due to the frequent re-circulation of blood and lack of endothelial cells, inhibition of FXI/FXIa by abelacimab prolonged time to circuit clotting, providing support for testing abelacimab in patients on hemodialysis.