Evaluation of bivalirudin treatment for heparin-induced thrombocytopenia in critically ill patients with hepatic and/or renal dysfunction.
OBJECTIVE
To evaluate the safety, effectiveness, and dosing of bivalirudin for treatment of heparin-induced thrombocytopenia (HIT) in critically ill patients with hepatic and/or renal dysfunction.


METHODS
Retrospective cohort study.


METHODS
University-affiliated medical center


METHODS
Eighteen patients older than 18 years who were admitted to the intensive care unit (ICU), had hepatic and/or renal dysfunction, and were treated with bivalirudin for the diagnosis of HIT between January 1, 2004, and March 31, 2005.


RESULTS
Patient records were reviewed for dosage and duration of bivalirudin therapy, occurrence of thrombosis, and clinically significant adverse effects. Of the 18 patients identified, 12 had both hepatic and renal dysfunction (group 1), four had hepatic dysfunction (group 2), and two had renal dysfunction (group 3). Demographics were similar among the groups. Mean +/- SD age was 54 +/- 15 years and weight was 82 +/- 14 kg, 67% were male, 83% were Caucasian, and 56% were receiving renal replacement therapy. Mean bivalirudin doses were 0.06 +/- 0.15 mg/kg/hour (median 0.03 mg/kg/hr), 0.14 +/- 0.05 mg/kg/hour (median 0.14 mg/kg/hr), and 0.05 +/- 0.01 mg/kg/hour (median 0.05 mg/kg/hr) for patients in groups 1, 2, and 3, respectively. Ten patients receiving continuous venovenous hemofiltration with or without dialysis received a mean dose of 0.04 +/- 0.03 mg/kg/hour (median 0.03 mg/kg/hr). In the 18 patients, mean bivalirudin duration was 15 +/- 17 days, activated partial thromboplastin time (aPTT) was 69 +/- 22 seconds, and international normalized ratio was 2.2 +/- 0.8. Supratherapeutic aPTTs were most common on days 1 (22%) and 2 (28%) when bivalirudin doses were highest. Clinically significant bleeding did not occur in any patient. Thrombosis occurred in one patient (6%) while receiving bivalirudin.


CONCLUSIONS
Patients in the ICU who have hepatic and/or renal dysfunction require low doses of bivalirudin to achieve aPTT values 1.5-2.5 times baseline. Bivalirudin can be safely started at 0.14 mg/kg/hour in patients with hepatic dysfunction, 0.03-0.05 mg/kg/hour in those with renal or combined hepatic and renal dysfunction, and 0.03-0.04 mg/kg/hour in patients receiving continuous renal replacement therapy.
Kiser
Tyree H
TH
Department of Clinical Pharmacy, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. ty.kiser@uchsc.edu
Fish
Douglas N
DN
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D016638:Critical Illness; D005260:Female; D006493:Heparin / Q000009:adverse effects; D006629:Hirudins / Q000009:adverse effects; D006801:Humans; D007362:Intensive Care Units; D007674:Kidney Diseases / Q000150:complications*; D008107:Liver Diseases / Q000150:complications*; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy*
D000925:Anticoagulants; D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D006493:Heparin; D013917:Thrombin; C074619:bivalirudin