Antithrombin Dose Optimization in Extracorporeal Membrane Oxygenation in Infants

Anticoagulation in extracorporeal membrane oxygenation (ECMO) is challenging, with significant morbidity and mortality associated with thrombotic complications. Unfractionated heparin (UFH) is commonly used, which depends on native antithrombin (AT) function to exert anticoagulant effects. Antithrombin deficiency is common in infants on ECMO and replacement with AT concentrate may be warranted. However, dosing recommendations in this population are limited. We conducted a retrospective review of patients <1 year of age who received recombinant AT (ATryn) while on UFH and ECMO between January 1, 2010 and December 31, 2017. Commonly used dosing equations were assessed to determine their ability to predict postdose AT levels. Patient AT levels were compared with equation-predicted postdose AT levels to determine a correlation. A total of 102 doses in 41 patients were used for analysis. Baseline mean AT level was 43% (±13%) and mean AT doses were 134 units (±58.1 units) or 40.5 units/kg (±18.7 units/kg). Median increase in the AT level was 8% (interquartile range 2-17%) with a mean postdose level of 52.6% (±14.2%). Weight-based dosing poorly correlated with postdose AT levels (r2 = 0.082). Postdose levels were best predicted when using an equation that included desired change in the AT level from baseline, the patient's weight, and added weight from the volume of the ECMO circuit (r2 = 0.427). Prospective studies are needed to evaluate optimal dosing strategies, safety, and efficacy of AT in this population.