Argatroban Anticoagulation in Critically III Patients

Abstract

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 μg/kg/min in the first 5 patients and 0.2 μg/kg/min in the subsequent 19 patients. Results: Infusion of argatroban 2 μg/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 μg/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 μg/kg/min in both groups. Conclusions: In critically ill patients with MODS, argatroban 2 μg/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.