Argatroban Dosing and Monitoring During PCI

For patients with or at risk for HIT undergoing PCI, argatroban should be started at an infusion dose of 25 mg/kg/min and a bolus of 350 mg/kg given over 3-5 min. The ACT should be checked 5-10 min after the bolus dose is completed. If the ACT is >300 s, the PCI may proceed. If the ACT is <300 s, an additional bolus dose of 150 mg/kg should be given and the infusion dose increased to 30 mg/kg/ min. If, however, the ACT is >450 s after the initial bolus, then the infusion dose should be reduced to 15 mg/kg/min. After any additional bolus or dosage adjustment, the ACT should be checked again after 5-10 min to confirm the patient attained a therapeutic ACT. During a prolonged procedure, additional ACTs should be obtained every 20-30 min. For patients requiring anticoagulation after the procedure, argatroban infusion may be continued at a reduced dose such as that recommended for the prophylaxis or treatment of thrombosis in HIT.

These dosing recommendations do not take into consideration the possible combination use of GPIIb/IIIa antagonists. Lower doses of argatroban, e.g., bolus dose of 250-300 mg/kg followed by an infusion dose of 15 mg/kg/min, provide adequate anticoagulation with an acceptable bleeding risk in combination with GPIIb/IIIa antagonists in patients without HIT (Jang et al., 2004).

High doses of argatroban should be avoided in patients with or at risk of HIT who require PCI and have clinically significant hepatic disease, including laboratory evidence such as aspartate aminotransferase or alanine aminotransfer-ase at least three times the upper limit of normal. Argatroban use during PCI has not been studied in such patients (Lewis et al., 2002; Jang et al., 2004).

Because argatroban equally prolongs the Hemochron ACT and HemoTec ACT (Iqbal et al., 2002), investigators in the PCI trials effectively used whichever ACT method was available at their sites to monitor anticoagulation (Lewis et al., 2002; Jang et al., 2004). Sheaths were removed when the ACT was less than 160 s.

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