Abstract Number: PB0166
Meeting: ISTH 2020 Congress
Background: Bleeding and thrombosis are the most common complications of veno-venous (V-V) ECMO support for patients with respiratory failure. ECMO requires anticoagulation to prevent clotting in the circuit, but heparin and other thrombin inhibitors significantly increase bleeding risk at therapeutic concentrations. Recent evidence suggests fXIa inhibition might prevent thrombosis with less bleeding risk.
Aims: We aimed to show that intravenous administration of EP-7041 prevents clotting in the ECMO membrane oxygenator while causing less bleeding than heparin.
Methods: The hound model of V-V ECMO employs standard tubing, pumps and oxygenator components (Medtronic). Animals were anesthetized and 14F cannulae were placed via cutdown in the jugular and femoral veins for venous drainage and return. Heparin and EP-7041 were dosed to target aPTT of 2× baseline (BL); diluent was administered to match active agent fluid volume as a negative control. Study drug boluses and infusions were started 30 min prior to initiation of ECMO to allow anticoagulation to reach steady-state. Low-flow (20 mL/kg/min) ECMO circulation was maintained for 2.5 hours or until pressure proximal to the oxygenator reached 350 mmHg due to clotting. Bleeding rates were determined by placing preweighed sponges on incision sites for 15 minutes at 30-minute intervals.
Results: Pressure increased in all groups during ECMO, but only the diluent control reached the system limit of 350 mmHg, requiring termination within 1 hour. Anticoagulation with heparin and EP-7041 maintained aPTT in the range of 1.5×-2.5× BL and prevented the circuit from clotting during the 2.5-hour ECMO run (Figure 1). Bleeding rates (Figure 2) and total measured blood loss during ECMO were >3× greater with heparin treatment vs. EP-7041-treatment. Data will be updated prior to presentation.
Conclusions: Compared with heparin, anticoagulation with EP-7041, a short-acting, potent and selective, small-molecule Factor XIa antagonist, prevents oxygenator clotting but maintains hemostasis in a canine ECMO model.
To cite this abstract in AMA style:Kurz MA, Pollack CV, J, Connors JM, Levy JH, Drummond C, Klein D, Josuns HD, Pielemeier R, Buchino J, Osborne P, Hayward NJ. Anticoagulation with the Novel, Small-molecule Factor XIa (fXIa) Antagonist, EP-7041, Prevents Oxygenator Clotting but Conserves Hemostasis in a Canine Extracorporeal Circulation (ECMO) Model [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/anticoagulation-with-the-novel-small-molecule-factor-xia-fxia-antagonist-ep-7041-prevents-oxygenator-clotting-but-conserves-hemostasis-in-a-canine-extracorporeal-circulation-ecmo-model/. Accessed October 25, 2020.
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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/anticoagulation-with-the-novel-small-molecule-factor-xia-fxia-antagonist-ep-7041-prevents-oxygenator-clotting-but-conserves-hemostasis-in-a-canine-extracorporeal-circulation-ecmo-model/