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

Pharmacotherapy - Tập 28 Số 9 - Trang 1115-1124 - 2008
Tyree H. Kiser1, Jessica C. Burch1, Patrick Klem2, Kathryn L. Hassell3
1Departments of Clinical Pharmacy, Denver, Colorado.
2University of Colorado Health Sciences Center, and the Department of Pharmacy, University of Colorado Hospital, Denver, Colorado.
3Medicine, Denver, Colorado.

Tóm tắt

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 (Clcr) greater than 60 ml/minute (12 patients, group 1); Clcr 30–60 ml/minute (11 patients, group 2); and Clcr 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 Clcr (r2 = 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 Clcr greater than 60 ml/minute, 0.08‐0.1 mg/kg/hour in patients with Clcr 30–60 ml/minute, and 0.03‐0.05 mg/kg/hour in patients with Clcr below 30 ml/minute or receiving continuous RRT is effective at achieving goal aPTT values in most patients.

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Pharmacotherapy

Tập 28 Số 9

1115-1124

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