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Antithrombin (AT) is essential as a cofactor for unfractionated heparin (UFH) to deliver its anticoagulant effect. AT deficiency may result in inadequate anticoagulation with UFH at usual doses. Acquired AT deficiency is common in acutely unwell children due to either decreased production (especially in infants with liver immaturity) or increased consumption. It is known that children require higher doses of UFH than adults to achieve andmaintain therapeutic levels of anticoagulation.1–3 In infants and children, the levels of AT are lower than in adults (may be as low as 10–30%) and AT may be consumed in illness.3 In a study by Andrew et al, it was shown that children<12months of age require a 50% higher UFH dose (28 U/kg/h) compared with children>12 months of age (20 U/kg/h) to achieve the same anticoagulant effect as measured by activated partial thromboplastin time (APTT).4 In another study, the median UFH dose required to achieve therapeutic anti-factor Xa (anti-Xa) levels in 83 infants was 33 U/kg/h and 39% of infants required at least one dose of AT supplementation (50–200 IU/kg) to achieve therapeutic heparin anti-Xa levels.5 However, the UFH requirement may also be increased by nonspecific binding of UFH to acute phase reactants. Both reduced levels of AT and accelerated heparin clearance are barriers to effective anticoagulation in children. Although the APTT is a cheap and easily available test that is commonly used for the monitoring of UFH, it may not provide an accurate measure of anticoagulant effect of heparin as a result of various confounding factors including both preanalytical and analytical variables.6 The anti-Xa assay is not as significantly affected by these confounding factors and so has been proposed as a better assay for monitoring UFH. Consequently, it is our standard practice to use the anti-Xa level to monitor UFH rather than the APTT in both pediatric and adult patients. Based on comparisons using an anti-Xa chromogenic assay within our hospital, an APTT of 60 to 100 seconds (using SynthASil reagent on ACL TOP 500 [Instrumentation Laboratory]) corresponds to the recommended anti-Xa therapeutic range of 0.3 to 0.7 IU/mL. In this retrospective single-center observational study in a tertiary pediatric intensive care unit in United Kingdom, we set out to determine whether AT supplementation could elevate AT levels, achieve therapeutic anticoagulation based on heparin anti-Xa, and reduce UFH dosage. This was undertaken as a service evaluation project and approved by the Trust Clinical Effectiveness Unit. We studied children with acquired AT deficiency who were acutely unwell following acute thrombosis, cardiac surgery due to congenital heart disease, and those requiring extracorporeal membrane oxygenation (ECMO) for severe respiratory or cardiac failure or both. From January 2016 to March 2019, all patients<16 years who received AT concentrate (ATC) for acquired AT deficiency were included for the study. Heparin anti-Xa activity was measured by chromogenic Liquid anti-Xa assay without exogenous AT, APTT was measured using SynthASil reagent, and AT concentration was measured using HemosIL Liquid Antithrombin (all from Werfen), on the same sample using an ACL TOP 500, before and 4 to 8hours after administration of ATC. The Clauss fibrinogen levelwas alsomeasured in the same sample using an FIB-C XL kit (Werfen) on the ACL TOP 500 analyzer. The decision to administer ATC was based on the patient who required anticoagulationwith UFH and failed to achieve therapeutic anticoagulation (measured by heparin anti-Xa) despite increasing the dose of UFH to>40 U/kg/h and was

Use of Antithrombin Concentrate for Acquired Antithrombin Deficiency in Acutely Unwell Children Receiving Unfractionated Heparin