Efficacy and safety of antithrombin supplementation in neonates and infants on a continuous heparin infusion

Background: Antithrombin (AT) is a natural anticoagulant and potent inhibitor of several coagulation proteins, including activated factor X (FXa) and FIIa. The therapeutic activity of heparin depends on the presence of AT. Levels of plasma AT are low in neonates and young infants compared to those in adults. Exogenous AT supplementation is postulated to enhance the activity of heparin and facilitate attainment of therapeutic anticoagulation in infants. Objectives: To describe the efficacy and safety of AT administration in infants on a continuous heparin infusion. Methods: Retrospective cohort study of 50 infants who received AT while on a heparin infusion. The primary efficacy outcome was attainment of therapeutic anticoagulation within 48 hours after AT administration. Secondary outcomes included the percent of partial thromboplastin time (PTT) levels and/or antifactor Xa (anti-FXa) activity within the therapeutic window, attainment of the target AT activity level, the incidence and severity of bleeding, and all-cause in-hospital mortality. A secondary analysis investigated the relationship between simultaneously measured PTT levels and anti-FXa activity used for heparin monitoring. Results: AT supplementation resulted in achievement of at least one therapeutic PTT level or anti-FXa activity in 90% of AT courses, though not sustained. PTT was within the therapeutic window more often than anti-FXa activity. When measured simultaneously, therapeutic anti-FXa levels were associated with supratherapeutic PTT levels. Conclusion: AT supplementation in infants on a continuous heparin infusion may transiently improve the therapeutic effect of heparin, but this is largely dependent on the laboratory parameters used for monitoring.