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An increasing number of pediatric patients suffer from thrombotic events necessitating anticoagulation therapy including heparins. Some such patients develop heparin-induced thrombocytopenia (HIT) and thus require alternative anticoagulation. As such, studies evaluating the safety, efficacy, and dosing of alternative anticoagulants are required.In this multicenter, single arm, open-label study, 18 patients ≤16 years old received argatroban for either a suspicion of or being at risk for HIT, or other conditions requiring nonheparin anticoagulation. Endpoints included thrombosis, thromboembolic complications, and bleeding.Patients (ages, 1.6 weeks to 16 years) received argatroban usually for continuous anticoagulation (n = 13) or cardiac catheterization (n = 4). One catheterization patient received a 250 μg/kg bolus only; 17 patients received argatroban continuous infusion (median (range)) 1.1 (0.3–12) μg/kg/min (of whom four received a bolus) for 3.0 (0.1–13.8) days. In patients without bolus dosing, typically argatroban 1 μg/kg/min was initiated, with therapeutic activated partial thromboplastin times (aPTTs) (1.5–3× baseline) achieved within 7 hr. Within 30 days, thrombosis occurred in five patients (two during therapy). No one required amputation or died due to thrombosis during therapy. Two patients had major bleeding. Pharmacometric analyses demonstrated the optimal initial argatroban dose to be 0.75 μg/kg/min (if normal hepatic function), with dose reduction necessary in hepatic impairment.In pediatric patients requiring nonheparin anticoagulation, argatroban rapidly provides adequate levels of anticoagulation and is generally well tolerated. For continuous anticoagulation, argatroban 0.75 μg/kg/min (0.2 μg/kg/min in hepatic impairment), adjusted to achieve therapeutic aPTTs, is recommended. Pediatr Blood Cancer 2011;56:1103–1109. © 2010 Wiley-Liss, Inc.