Argatroban

Argatroban (see Chapter 15) is a synthetic direct thrombin inhibitor that binds reversibly to the active site of thrombin. In adults, the recommended initial dose of argatroban is 2 mg/kg/min given by continuous i.v. infusion and adjusted by aPTT (target range, 1.5-3 times the baseline aPTT). Argatroban also prolongs the international normalized ratio (INR), which makes subsequent transition to vitamin K antagonist therapy, if required, more difficult.

Safety and efficacy of argatroban in pediatric patients have not been established. However, there are several case reports and a chart review (Liedel et al., 2003). Hursting et al. (2006) conducted a comprehensive search and critical analysis of the literature on argatroban use in 34 children. Overall, the patients were between 1 wk and 16 yr of age. All patients received a continuous i.v. infusion of argatroban, titrated to achieve a target aPTT. The aPTT-adjusted doses ranged from 0.1 to 12 mg/kg/min. Four patients also received an initial argatroban bolus of 75200 mg/kg. Bleeding occurred in three patients while on argatroban. In neonates (Kawada et al., 2000; Okada et al., 2000; Boshkov et al., 2003a,b) an argatroban bolus of 200-250 mg/kg is reported followed by a continuous infusion rate of 7.5-10 mg/kg/min. Of note, this dose is much higher than the 1-2 mg/kg/min recommended in adults. In a newborn, argatroban was used for anticoagulation during extracorporeal membrane oxygenation (ECMO). After an initial bolus of 200 mg/kg, a continuous infusion at a rate of 3.0-7.5 mg/kg/min was started. During use of a ventricular assist device (VAD), safe anticoagulation with argatroban could be achieved in this infant with an infusion rate of 0.05-1.8 mg/kg/min (Mejak et al., 2004).

The literature reviewed by Hursting et al. (2006) provides information regarding argatroban dosing during CPB, ECMO, VAD use, hemodialysis, and cardiac catheterization. In general, although generally safe anticoagulation with argatroban was reported, further evaluation of the efficacy and safety of argatro-ban in pediatric patients is needed to make further recommendations.

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