The use of extracorporeal membrane oxygenation (ECMO) circuit obligates the administration of systemic anticoagulation to avoid patient and circuit thrombosis. Identifying an optimal approach for achievement of target pharmacologic anticoagulation remains elusive with controversy existing between the ideal agent employed, dosing protocols, monitoring approaches, and supplemental therapies including antithrombin (AT) administration in the context of unfractionated heparin (UFH) therapy.¹ With this in mind, we read with great interest the salient study by Liviskie et al. investigating the effectiveness of AT dosing equations to predict postdose AT levels in a cohort of 41 pediatric patients under 1 year of age.² Important findings included a low baseline mean AT level of 43% (±13%) and mean postdose AT level of 52.6% (±14.2%) with poor correlation using weight-based dosing equations (R² = 0.082) that improved with integration of desired change in AT level from baseline augmented with adjustments of the patients’ weight supplemented with an adaptation utilizing the estimated weight from the volume of the ECMO circuit (R² = 0.427). We applaud the authors for providing highly granular detail on AT dosing on a relatively large number of infant ECMO patients along with the concurrent analysis leveraging a robust quantity of prediction equations that included commonly accepted as well as manufacturer recommended and institutional adjusted calculations. Although intriguing data, the clinical appropriateness of AT replacement or its broader implications into the broader context of systemic anticoagulant administration during ECMO support remain unclear.