Safety, Efficacy, and Dosing Requirements of Bivalirudin in Patients with Heparin‐Induced Thrombocytopenia

STUDY OBJECTIVE: To evaluate the safety, efficacy, and dosing requirements of bivalirudin in patients with heparin-induced thrombocytopenia (HIT). DESIGN: Retrospective cohort study. SETTING: University-affiliated hospital. PATIENTS: Thirty-seven adults with a diagnosis or history of HIT who were treated with bivalirudin between January 1, 2004, and March 31, 2007. MEASUREMENTS AND MAIN RESULTS: Patients had a mean +/- SD age of 50 +/- 16 years and weighed 80 +/- 20 kg; 62% were male, 73% were Caucasian, and 95% were treated in the intensive care unit. Patients were divided into three renal function groups for assessment of bivalirudin dosing requirements: creatinine clearance (Cl(cr)) greater than 60 ml/minute (12 patients, group 1); Cl(cr) 30-60 ml/minute (11 patients, group 2); and Cl(cr) lower than 30 ml/minute or receiving continuous renal replacement therapy ([RRT] 14 patients, group 3). Except for renal function, baseline demographic characteristics were similar among groups. A total of 19 (51%) of the 37 patients achieved goal activated partial thromboplastin time (aPTT) with initial mean +/- SD bivalirudin doses of 0.14 +/- 0.04 (median 0.15), 0.1 +/- 0.07 (median 0.08), and 0.05 +/- 0.05 (median 0.05) mg/kg/hour in groups 1, 2, and 3, respectively. Doses remained similar over the study period and were 0.13 +/- 0.04 (median 0.15), 0.1 +/- 0.06 (median 0.1), and 0.04 +/- 0.02 (median 0.03) mg/kg/hour for groups 1, 2, and 3, respectively. The mean +/- SD aPTT value after achieving goal range was 64 +/- 9 seconds (all patients). Bivalirudin dosing requirements correlated with Cl(cr) (r(2) = 0.37, p<0.0001). Therapy duration was a mean +/- SD of 11 +/- 13 days (median 7 days). Systemic thrombosis and bleeding while receiving bivalirudin were also evaluated. Thrombosis occurred in one patient; clinically significant bleeding occurred in two patients. CONCLUSION: Bivalirudin dosing requirements correlated with renal function; therefore, dosage reduction is required in patients with moderate or severe renal dysfunction. Starting bivalirudin at 0.15 mg/kg/hour in patients with Cl(cr) greater than 60 ml/minute, 0.08-0.1 mg/kg/hour in patients with Cl(cr) 30-60 ml/minute, and 0.03-0.05 mg/kg/hour in patients with Cl(cr) below 30 ml/minute or receiving continuous RRT is effective at achieving goal aPTT values in most patients.