The objective of this study was to assess the required dose and anticoagulatory effect of argatroban (Mitsubishi, Pharma Deutschland GmbH, Düsseldorf, Germany), a direct thrombin inhibitor approved for anticoagulation in patients with heparin-induced thrombocytopenia (HIT) undergoing extracorporeal membrane oxygenation (ECMO). Nine consecutive patients undergoing ECMO for severe acute respiratory distress syndrome (ARDS) and presenting with suspected HIT were treated with a continuous argatroban infusion. Coagulation variables were measured and dose adjustments of argatroban were performed to target for an activated partial thromboplastin time (aPTT) of 50 to 60 s. The first patient received argatroban 2 microg/kg/min as recommended by the manufacturer. This resulted in excessive anticoagulation and severe bleeding. The consecutive eight patients received a 10-fold lower dose (0.2 microg/kg/min). This dose sufficiently increased aPTT time from 46 +/- 6 s to 65 +/- 14 s (P < 0.001) and thrombin time from 18 +/- 8 s to 45 +/- 11 s (P = 0.001). The maintenance dose averaged 0.15 microg/kg/min. Duration of argatroban infusion for ECMO averaged 4 +/- 1 days and no oxygenator or extracorporeal system clotting was observed. In three of nine patients (33%), HIT was confirmed. Argatroban is a feasible and effective anticoagulant for patients with suspected HIT undergoing ECMO. However, a dose 10-fold lower than that recommended by the manufacturer is sufficient to achieve appropriate anticoagulation in critically ill patients undergoing ECMO.