Argatroban therapy in heparin-induced thrombocytopenia with hepatic dysfunction

Study objectives: We evaluated the dosing requirements in argatroban-treated patients with thrombocytopenia (HIT) and hepatic dysfunction, and compared efficacy and safety outcomes with historical control patients. Design: Retrospective analysis. Setting: Inpatient setting. Patients: Patients with hepatic dysfunction, defined as total bilirubin > 25.5 mu mol/L (1.5 mg/dL), aspartate aminotransfrase > 100 IU/L, and/or alanine aminotransferase > 100 IU/L, were identified from previous multicenter, historical-controlled studies of argatroban therapy, in HIT. Interventions: Argatroban, adjusted to maintain activated partial thromboplastin times (aPTTs) 1.5 to 3 times. baseline in the experimental group, vs no direct thrombin inhibition in the historical control patients. Measurements and results: The analysis population included 82 argatroban patients and 34 historical control patients with hepatic impairment, of whom approximately 50% in each group had renal dysfunction (defined as a serum creaetinine level > 1.3 mg/dL). The argatroban dosage was 1.6 +/- 1.1 mu g/kg/min (mean +/- SD) over a mean 5-day course of therapy. Significantly, lower doses were, used in patients with elevated vs normal total bilirubin levels (0.8 +/- 0.6 mu g/kg/min vs 1.7 +/- 0.8 mu g/kg/min, p=0.0063) and in patients with hepatic/renal dysfunction vs hepatic dysfunction alone (1.2 +/- 1.1 mu g/kg/min vs 2.0 +/- 1.1 mu g/kg/min, p < 0.001). The aPTT 24 h after argatroban initiation was 69 +/- 22 s, with 80% of patients having a therapeutic level of anticoagulation. Thirty-four argatroban-treated patients (41.5%) and 17 control patients (50.0%) experienced the 37-day composite end point of death, amputation, or new thrombosis (p = 0.32). Argatroban significantly reduced new thrombosis (8.5% vs 26.5%, p = 0.012). Major bleeding was similar between treatment groups (4.9% vs 2.9%, p = 0.684). Conclusions: Hepatic dysfunction affects argatroban dosing, with reduced doses required particularly in patients with serum total bilirubin levels > 25.5 mu mol/L (1.5 mg/dL) or combined hepatic/renal dysfunction. Individual mean aPTT-adjusted doses typically remain >= 0.5 mu g/kg/ min, supporting the recommendation of 0.5 mu g/kg/min as a conservative initial dose for most Patients with hepatic impairment Argatroban, with proper initial dosing and monitoring, can provide safe and effective antithrombotic therapy in patients with HIT and hepatic impairment.