Evaluation of Systemic Heparin Versus Bivalirudin in Adult Patients Supported by Extracorporeal Membrane Oxygenation

Abstract

Systemic anticoagulation is a standard of care in adult patients supported by extracorporeal membrane oxygenation (ECMO) to prevent circuit thrombosis and subsequent thromboembolic events. Unfractionated heparin has long been considered the anticoagulant of choice, but emerging evidence reports successful ECMO runs with direct thrombin inhibitors. This retrospective study sought to determine whether bivalirudin offers distinct clinical benefits as the anticoagulant of choice in ECMO. Primary end points included thrombotic events during the initial 96 hours of anticoagulation, over the course of their entire ECMO run, and at any time during the admission, as well as in-hospital and 30-day mortality. Secondary end points included percent time within therapeutic range for each anticoagulant, neurologic events, vascular complications, and bleeding. Compared with patients receiving heparin, patients receiving bivalirudin show similar rates of thrombotic events across the three time points (17.9% vs. 9.1%; p = 0.47, 21.4% vs. 11.4%; p = 0.41, and 25% vs. 22.7%; p = 1.00, respectively). In-hospital (32.1% vs. 36.4%; p = 0.91) and 30-day mortality (32.1% vs. 36.4%; p = 0.91) were no different. Similarly, no differences were observed in percent time within therapeutic range (83.0% vs. 87.7%, p = 0.34), neurological events (7.1% vs. 11.4%, p = 0.99), vascular complications (57.1% vs. 38.6%, p = 0.20), or major (25.0% vs. 45.5%, p = 0.13) and minor (25.0% vs. 22.7%, p = 1.00) bleeding. These results suggest that bivalirudin is a viable alternative to heparin for anticoagulation in ECMO but may not offer a clinically significant advantage as the anticoagulant of choice.

Hemostatic Management of Extracorporeal Circuits Including Cardiopulmonary Bypass and Extracorporeal Membrane Oxygenation

“…Many institutions use heparin as their primary anticoagulant, but recently some institutions have started using bivalirudin instead of heparin. 69 While heparin requires binding to antithrombin and heparin cofactor II for anticoagulant action, bivalirudin has a direct effect, does not need to bind to other proteins to show anti-thrombin action, and, therefore, has a more stable effect. 70,71 In addition, release of tissue factor pathway inhibitor by heparin is another significant contributor to anti-Xa action.…”

Heparin vs bivalirudin anticoagulation for extracorporeal membrane oxygenation

“…Bohman et al 5 showed similar thrombotic event rates and blood loss between heparin and bivalirudin. Berei et al 6 depicted similar rates of thrombotic events between the two agents and no differences were observed in percent time activated partial thromboplastin time (aPTT) within the therapeutic range, neurological events, vascular complications, or major and minor bleeding incidents. Given the limited evidence on the efficacy and safety profiles of UFH compared with bivalirudin, this retrospective study aims to analyze the rates of composite thrombotic complications, major bleeding, and mortality events in patients who were supported by ECMO and received heparin‐ or bivalirudin‐based anticoagulation.…”

“…Bohman et al 5 showed similar thrombotic event rates and blood loss between heparin and bivalirudin. Berei et al 6 depicted similar rates of thrombotic events between the two agents and no differences were observed in percent time activated partial thromboplastin time (aPTT) within the therapeutic range, neurological events, vascular complications, or major and minor bleeding incidents.…”

Extracorporeal Strategies in Acute Respiratory Distress Syndrome

“…Heparin pharmacokinetics and pharmacodynamics are highly variable as it binds proteins and cells relatively indiscriminately, as it is eliminated through various mechanisms (including endothelial and macrophage metabolism) and as it exerts its effect through antithrombin III, which can often become deficient in patients on ECLS. 58 The parameter to use for monitoring and its target are still uncertain. 50 Common parameters for titrating anticoagulation include activated clotting time (ACT) or activated partial thromboplastin time (aPTT).…”