Impact of Nitric Oxide Anticoagulation on Thrombogenicity in an Ovine Model of Venovenous Extracorporeal Life Support – UROP Spring Symposium 2025

Impact of Nitric Oxide Anticoagulation on Thrombogenicity in an Ovine Model of Venovenous Extracorporeal Life Support

George Boville

Research Mentor(s): Orsolya Lautner-Csorba
Mentor Department: Urop Ecls Student
Authors: George Boville, Jensyn VanZalen, Ryan Kauffman, Temilolaoluwa Daramola, Daniela Pelaez Palacio, Gergely Lautner Lautner, Robert Bartlett, Orsolya Lautner-Csorba, Alvaro Rojas-Peña
Session: Session 5 (2:00pm – 2:50pm)
Presentation Type: Poster 81

Abstract

Introduction: Extracorporeal membrane oxygenation (ECMO) is utilized for patients facing severe cardiac or respiratory failure. Although systemic anticoagulants are administered during ECMO to inhibit clotting, thrombus formation can still occur. Additionally, there is a risk of hemorrhagic complications. The vascular endothelium produces nitric oxide (NO) by deactivating platelets and mitigating clot formation, therefore it is proposed that NO may work as a local anticoagulant with reduced bleeding-related complications compared to systemic anticoagulation. Methods: 10 sheep (40-50 kg, 50% male 50% female) were anesthetized and vascular access for venovenous (VV) ECMO was obtained via the right jugular vein (drainage) and right femoral vein (reinfusion). Additionally, an arterial line was inserted to monitor the animal’s hemodynamics. Animals were assigned to one of the following groups: 1) Control (n=4), standard ECMO system with systemic anticoagulation with heparin; 2) NO-g (n=3), Standard ECMO system with 100 ppm NO gas; 3) NO-r (n=3): NO-releasing coated (DBHD+Argatroban) ECMO circuit plus 100 ppm NO gas. Animals were studied for 14 days or until 2 to 3 end-criteria were met (ex. device resistance 5x baseline; >50% decrease of ECMO blood flow after adjusting RPMs; post-oxygenator sO2% < 95%; and animal hemodynamic instability/distress). Data collected: Circuit patency, platelet count (PLT), platelet aggregation (PA%), activated clotting time (ACT), Fibrinogen, and D-dimers. T-tests were performed to determine whether data is statistically significant (p=<0.05). Results: The average ECMO circuit patency was 124.6±59.3 hours for the control group, compared to 215.5±128.6 hours for the NO-g group and 312.3±40.9 hours for the NO-r group. Only the NO-r group's patency was significantly longer than that of the control (p=0.002). Hemorrhagic complications occurred in all control animals (25% thoracic, 75% groin). After 7 days of ECMO, normalized PLT were 121.1±0% for the control, 273.4±86.0% for NO-g, and 107.0±11.8% for NO-r. The average PA% was 62±16% for control, 70±9% for NO-g, and 68±16% for NO-r; the control group had significantly lower PA% compared to both NO groups (vs. NO-r p=0.001; vs. NO-g p=0.022), with no differences between the NO groups (p=0.407). The average ACTs were 259.6±5.7 seconds for the control, 166.3±9.7 seconds for NO-g, and 175.8±7.8 seconds for NO-r, with systemic anticoagulation ranges observed only in the control group. Fibrinogen and D-Dimer values are pending analysis Conclusion: The data shows that ECMO circuits utilizing NO release and NO-gas addition to the oxygenator maintain circuit patency for over 10 days without hemorrhagic complications, eliminating the need for systemic anticoagulation in this ovine model. Additionally, NO use during ECMO support accelerates platelet count recovery and preserves platelet function, highlighting its potential as a superior alternative to traditional systemic anticoagulants.

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