Clinical trial of argatroban, a direct thrombin inhibitor, as an anticoagulant in cardiopulmonary support and apheresis in emergency patients: a preliminary report

Abstract

 To evaluate the safe and effective use of argatroban, a competitive direct thrombin inhibitor, as an alternative anticoagulant for percutaneous cardiopulmonary support (PCPS) and continuous hemofiltration or hemodiafiltration (CHF/CHDF), a preliminary multicenter clinical trial was conducted between October 1999 and September 2000. Nine patients who underwent PCPS and/or CHF/CHDF were enrolled in the study during this period. The dosage of argatroban was controlled so that the activated clotting time (ACT) was maintained at around 180 to 200 s. The mean duration of argatroban administration was 82 ± 92 h, and the mean dose was 0.67 ± 0.40 μg kg⁺¹ min⁻¹. Severe hemorrhagic complications requiring the discontinuation of argatroban administration were not observed in any of the patients. Platelet loss was prevented to some degree, and plasma levels of fibrinogen were well preserved during PCPS/CHDF. Except for two patients undergoing CHDF, clot formation within the extracorporeal circulation circuit was not identified macroscopically after the discontinuation of the procedures. We conclude that argatroban might be useful as an alternative anticoagulant in cases where heparin cannot be safely used because of the increased risk of bleeding complications, thrombocytopenia, and/or hypofibrinogenemia. Although the optimal dose of argatroban has not been established, we propose an initial starting dose of 0.7 to 1.0 μg kg⁻¹ min⁻¹, followed by adjustments to maintain an ACT of between 180 and 250 s.