Argatroban anticoagulation in critically ill patients

BACKGROUND: Despite long-term use of argatroban in clinical practice, no dosing recommendations exist for critically ill patients with multiple organ dysfunction (MODS) and suspected or proven heparin-induced thrombocytopenia (HIT). OBJECTIVE: To determine the suitability of argatroban use in critically ill patients with MODS and HIT METHODS: We conducted prospective observation of 24 consecutive patients with suspected HIT who were being anticoagulated with argatroban (target activated partial thromboplastin time [aPTT] 1.5-2 times normal or 50-60 sec) using 2 mu g/kg/min in the first 5 patients and 0.2 mu g/kg/min in the subsequent 19 patients. RESULTS: Infusion of argatroban 2 pg/kg/min over 4 hours caused bleeding complications in 3 patients as aPTT increased from 51 18 to 86 34 seconds (p = 0.02), prothrombin time (PT) decreased from 76 +/- 27% to 33 +/- 12% of normal reference values, and international normalized ratio (INR) increased from 1.4 +/- 0.4 to 2.5 +/- 0.9 (p = 0.007). Infusion of argatroban 0.2 mu g/kg/min over 4 hours provided sufficient anticoagulation without bleeding complications. The aPTT in this population increased from 44 9 to 59 13 seconds (p < 0.001), and PT and INR remained unchanged (76 +/- 22% and 69 +/- 23% of normal reference values, 1.3 +/- 0.3 and after 1.3 +/- 0.3, respectively [p = 0.4]). Coagulation variables (aPTT, PT, INR) were significantly different between both dosing regimens after 4 hours of infusion (p = 0.042 and p = 0.003, respectively). The maintenance dose for target aPTT averaged 0.22 +/- 0.15 mu g/kg/min in both groups. CONCLUSIONS: In critically ill patients with MODS, argatroban 2 pg/kg/min, as recommended by the manufacturer, resulted in extensive anticoagulation. A tenfold lower starting dose is sufficient and safe for effective anticoagulation in this specific patient population.