The factor XI/XIa antibody abelacimab combined with enoxaparin inhibits filter clotting in hemodialysis circuits ex vivo

Abstract

Drugs targeting factor XI may offer an alternative to heparin for preventing blood clotting in extracorporeal circulation. We investigated the effects of abelacimab, a novel monoclonal antibody targeting factor XI. We collected whole blood samples into two bags (each 240 ml, control group: enoxaparin 1.2 mg, treatment group: enoxaparin 1.2 mg plus abelacimab 5 mg) and circulated in a hemodialysis device for up to 3 h. We performed whole blood aggregation and thromboelastometry at several time points. Time to filter clotting was the primary endpoint. We included 10 volunteers. Each volunteer’s blood was split into two bags (containing enoxaparin +/- abelacimab) and used simultaneously on two hemodialysis devices. The treatment group’s time to filter clotting was significantly prolonged (treatment: 180 min, IQR 180–180 vs. control: 120 min, IQR 97–147, p < 0.001), and the transmembrane pressure was significantly lower at the end of the circuit flow (treatment: 13 mmHg vs. control: 65 mmHg, p = 0.001). Fibrinogen levels and median platelet counts were preserved. Platelet aggregation was better preserved in the treatment group for ristocetin (p = 0.015), thrombin receptor activating peptide (p = 0.015), and arachidonic acid (p = 0.001). Thromboelastometry showed prolonged clotting times in the treatment group at the end of the experiment (INTEM, p < 0.001; HEPTEM, p = 0.001). Abelacimab prolonged the time to filter clotting in this ex vivo model of hemodialysis. This is an aggressive model due to the frequent re-circulation of blood and a lack of endothelial cells. These data provide support for testing abelacimab in patients on hemodialysis.