Extracorporeal membrane oxygenation (ECMO) is a mechanical circulatory and respiratory support system that facilitates gas exchange and hemodynamic stabilization through an external circuit. ECMO has been increasingly utilized for the management of refractory respiratory and cardiac failure, providing critical time for organ recovery or transplantation [Citation1]. During ECMO, blood is drained from the patient’s venous system, passes through a centrifugal pump and oxygenator, and is then reinfused into the venous or arterial system. However, prolonged exposure to non-biological circuit surfaces activates the coagulation cascade, increasing the risk of thrombotic complications. As a result, systemic anticoagulation is required, but excessive anticoagulation raises the risk of life-threatening hemorrhage.

Unfractionated heparin (UFH) remains the most commonly used systemic anticoagulant in ECMO [Citation2]. Heparin binds to antithrombin (AT), forming a complex that enhances the inhibition of multiple coagulation factors, including thrombin (factor IIa, factor Xa, factor XIIa, factor XIa, and factor IXa) [Citation3,Citation4]. However, up to 50% of ECMO patients experience heparin resistance, often due to acquired AT deficiency, which diminishes heparin’s anticoagulant effect [Citation5,Citation6]. This issue is particularly pronounced in pediatric patients, where acquired AT deficiency and heparin resistance are more frequent. Neonates are born with only 50% of adult AT levels, and preterm infants exhibit even lower AT activity. AT levels typically reach adult concentrations by 6–12 months of age [Citation7,Citation8]. In cases of heparin resistance, increasing heparin dosing fails to achieve expected anticoagulation targets, such as activated clotting time (ACT), activated partial thromboplastin time (APTT), or anti-Xa levels, resulting in either inadequate or excessive anticoagulation. In such scenarios, AT III supplementation has been proposed as a strategy to restore heparin responsiveness, optimize anticoagulation, and achieve therapeutic anticoagulation with lower heparin doses [Citation9].

However, the safety and efficacy of AT III supplementation in ECMO remain uncertain, and routine AT III administration is still debated [Citation10]. Therefore, this study aims to systematically evaluate and analyze the effects of AT III supplementation on in-hospital mortality, bleeding, and thrombotic complications in ECMO patients.