Clinical experience with argatroban for heparin-induced thrombocytopenia in a large teaching hospital

Background:

Argatroban is a direct thrombin inhibitor approved for the prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia (HIT). The product monograph does not guide clinicians beyond specifying the initial dose of 2 μg/kg per minute (or 0.5 μg/kg per minute for patients with hepatic impairment). Some authors have suggested that in the intensive care unit (ICU) and for patients with acute cardiac disease and those with renal or hepatic dysfunction, this dose may result in a supratherapeutic activated partial thromboplastin time (aPTT).

Objectives:

To evaluate the efficacy and safety of argatroban in adult patients with suspected HIT in a large teaching hospital, and to review dosing for patients in the ICU, patients with acute cardiac disease, and patients with renal or hepatic dysfunction.

Methods:

Charts of patients with suspected HIT who had received argatroban for at least 24 h between October 1, 2005, and October 1, 2007, at the Foothills Medical Centre, Calgary, Alberta, were examined retrospectively.

Results:

Thirty patients met the inclusion criteria, with charts available for review. Of these, 21 (70%) patients had an initial argatroban dose of 2 μg/kg per minute and 4 (13%) had an initial dose of 0.5 μg/kg per minute. The median duration of therapy was 6 days, and the mean dose was 2.14 μg/kg per minute. There were 122 dosage adjustments, the most common change being 0.5 μg/kg per minute, followed by adjustments of 1 and 0.1 μg/kg per minute. Six patients had supratherapeutic aPTT values (above 100 s), and none experienced major bleeding.

Conclusions:

The results of this study suggest that an initial argatroban dose of 2 μg/kg per minute is appropriate for patients with no hepatic dysfunction. Patients with acute cardiac disease and critically ill patients may require lower doses of argatroban; however no dosage adjustments are required for patients with renal dysfunction.