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 microg/kg/min in the first 5 patients and 0.2 microg/kg/min in the subsequent 19 patients.

RESULTS

Infusion of argatroban 2 microg/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 microg/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 microg/kg/min in both groups.

CONCLUSIONS

In critically ill patients with MODS, argatroban 2 microg/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.