Argatroban Dose Reductions for Suspected Heparin-Induced Thrombocytopenia Complicated by Child-Pugh Class C Liver Disease

Abstract

To report our experience of reduced-dose argatroban in a patient with suspected heparin-induced thrombocytopenia (HIT) and Child-Pugh class C liver disease and review the relevant literature to summarize current recommendations on argatroban use in patients with severe liver disease. A 58-year-old male with Child-Pugh class C liver disease (Model for End-Stage Liver Disease [MELD] score = 31, total bilirubin 4.5 mg/dL) and hemodialysis-dependent renal failure was hospitalized with acute deep vein thrombosis (DVT). Three days after heparin initiation for DVT, he developed thrombocytopenia. Given his heparin exposure (both for treatment of DVT and ongoing hemodialysis), HIT was suspected and all heparinoids were immediately discontinued. Argatroban was initiated for the treatment of HIT while laboratory testing for HIT antibodies and the serotonin release assay were completed. Because of the patient's advanced liver disease, the starting dose of argatroban was reduced to 0.2 μg/kg/min, with frequent monitoring of the activated partial thromboplastin time (aPTT) (goal 60-85 seconds). Despite this dose reduction, the aPTT was supratherapeutic. Following further dose reductions, a final argatroban maintenance dose of 0.05 μg/kg/min was necessary for the attainment of goal aPTTs. Reducing the starting dose of argatroban to 0.5 μg/kg/min is recommended in patients with liver disease. Nevertheless, this recommended dose is largely based on data from patients with more moderate liver disease (eg, Child-Pugh class A or B), and dosing in more advanced liver disease remains largely unexplored. Patients with more advanced liver disease may require additional dose reductions to avoid supratherapeutic concentrations of anticoagulation agents and to minimize bleeding risk. This report illustrates the importance of careful selection of argatroban dosing and appropriate aPTT monitoring in patients with severe liver disease. Excessive anticoagulation may precipitate major bleeding complications, placing patients with this complicated disease at undue risk.