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 tr...

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Bibliographic Details
Published in:	Pharmacotherapy Vol. 28; no. 9; pp. 1115 - 1124
Main Authors:	Kiser, Tyree H., Burch, Jessica C., Klem, Patrick M., Hassell, Kathryn L.
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-09-2008 Pharmacotherapy
Subjects:	Adolescent Adult Aged Aged, 80 and over Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Anticoagulants - administration & dosage Anticoagulants - adverse effects Anticoagulants - therapeutic use anticoagulation Biological and medical sciences bivalirudin bleeding Clcr Cohort Studies Creatinine - blood creatinine clearance direct thrombin inhibitor dose Dose-Response Relationship, Drug Emergency and intensive care: renal failure. Dialysis management Female Heparin - adverse effects heparin-induced Hirudins - administration & dosage Hirudins - adverse effects HIT Humans Intensive care medicine Kidney Function Tests Male Medical sciences Middle Aged Partial Thromboplastin Time Peptide Fragments - administration & dosage Peptide Fragments - adverse effects Peptide Fragments - therapeutic use Pharmacology. Drug treatments platelet Recombinant Proteins - administration & dosage Recombinant Proteins - adverse effects Recombinant Proteins - therapeutic use renal function renal replacement therapy Retrospective Studies RRT thrombocytopenia Thrombocytopenia - chemically induced Thrombocytopenia - drug therapy thrombus Treatment Outcome Young Adult Renal function bleeding Peptides Toxicity Thrombus anticoagulation Thrombin Anticoagulant Bivalirudin Clearance Antithrombin Hemorrhage Posology Heparin induced thrombocytopenia Extrarenal dialysis RRT Clcr Complication Safety Dose Creatinine Human renal replacement therapy Serine endopeptidases Enzyme Treatment efficiency heparin-induced thrombocytopenia Enzyme inhibitor creatinine clearance direct thrombin inhibitor Peptidases Platelet HIT Treatment Polypeptide Glycosaminoglycan Hydrolases Heparin Pharmacokinetics
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Summary:	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.
Bibliography:	ArticleID:PHAR507 istex:32FF59695A1748DFDDB8BD9E763985BADB209017 ark:/67375/WNG-54MGB0DT-L
ISSN:	0277-0008 1875-9114
DOI:	10.1592/phco.28.9.1115