Cardiovascular Surgery or ECMO

Case reports describe patients with HIT or a history of HIT in whom argatroban anticoagulation has been used successfully during cardiopulmonary bypass (CPB) (Edwards et al., 2003; Martin et al., 2005), peripheral vascular surgery (Tokuda et al., 2003), carotid endarterectomy (Hallman et al., 2005), and off-pump coronary artery bypass surgery (Arnoletti and Whitman, 1999; Ide et al., 2001; Kieta et al., 2003; Ohno et al., 2003). Prolonged coagulopathy following CPB (Gasparovic et al., 2004), a high bleeding risk in pediatric patients undergoing CPB (Hursting et al., 2006), and thrombosis during off-pump cardiac surgery (Cannon et al., 2004) have also been reported. Dosing guidelines for argatroban use during adult cardiac surgery that have been proposed based on retrospective analysis of 21 published cases suggest an initial dose of 5 mg/kg/min (and a 100 mg/kg bolus for on-pump surgery), adjusted to target ACTs of 300-500 s for off-pump surgery and 400-600 s for on-pump surgery, with the ACT checked every 15 min (Martin et al., 2007). A safe, effective dose however has not been prospectively established.

For patients with previous HIT who undergo cardiac surgery using brief heparin exposure, treatment guidelines recommend using a nonheparin agent for perioperative anticoagulation (Warkentin and Greinacher, 2004). Reduced doses of argatroban may be needed following cardiac surgery because of possible decreased hepatic perfusion (Reichert et al., 2003; Czyz et al., 2006; Koster et al., 2006).

In vitro studies indicate that argatroban may be more efficacious than heparin in preventing thrombin generation in ECMO circuits (Young et al., 2004). The successful use of argatroban anticoagulation in patients with or at risk of HIT undergoing ECMO has been described, including an adult patient (Johnston et al., 2002) and 12 pediatric patients (Hursting et al., 2006). ECMO was continued in one of the pediatric patients, a neonate, for 78 days (Kawada et al., 2000). In each case, ACTs were typically maintained >180 s, although further study is required to establish dosing recommendations.

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