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Extensive Prolongation of aPTT with Argatroban in an Elderly Patient with Improving Renal Function, Normal Hepatic Enzymes, and Metastatic Lung Cancer

Pharmacy Practice Resident, Department of Pharmacy, Brigham and Women's Hospital, Boston, MA

Paul M Szumita, PharmD BCPS

Clinical Pharmacy Practice Manager, Department of Pharmacy, Brigham and Women's Hospital

John R Fanikos, BSPharm MBA

Assistant Director of Pharmacy Services, Department of Pharmacy, Brigham and Women's Hospital

Reprints: Dr. Kubiak, Department of Pharmacy—Tower L2, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115-6110, fax 617/566-2396, dwkubiak{at}partners.org

OBJECTIVE: To report a case of an elderly male with improving renal function and normal hepatic function who sustained an elevated activated partial thromboplastin time (aPTT) after an infusion of argatroban was discontinued.

CASE SUMMARY: A 77-year-old white male with a history of heparin-induced thrombocytopenia (HIT) and metastatic lung disease was started on argatroban for treatment of a right upper-extremity deep vein thrombosis (DVT). The infusion was initiated at 2.0 µg/kg/min and was titrated to a goal aPTT of 60-80 seconds. Argatroban was discontinued due to an aPTT elevated to >100 seconds; the aPTT remained elevated for 130 hours after discontinuation of the infusion.

DISCUSSION: Argatroban dose reductions in patients with impaired liver and renal function test values have been reported. Elderly subjects may have a prolonged clearance compared with young healthy subjects, although the duration of effect has not been established. As of April 18, 2005, the effect of liver metastasis on argatroban pharmacokinetics in the setting of normal liver function enzyme levels has not been reported. An objective causality assessment using the Naranjo probability scale showed that the prolonged aPTT was probably attributable to argatroban.

CONCLUSIONS: Clinicians should exercise caution when initiating argatroban at a dose of 2.0 µg/kg/min in elderly patients with underlying comorbidities, such as metastatic disease and renal impairment, since this may lead to excessive and prolonged anticoagulation and increased risk of bleeding.

Key Words: activated partial thromboplastin time, argatroban, heparin-induced thrombocytopenia

Published Online, May 10, 2005. www.theannals.com, DOI 10.1345/aph.1G020

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				S. A Spinler and W. Dager Comment: extensive prolongation of aPTT with argatroban in an elderly patient with improving renal function, normal hepatic enzymes, and metastatic lung cancer Ann. Pharmacother., November 1, 2005; 39(11): 1955 - 1956. [Full Text] [PDF]