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Argatroban for Heparin-Induced Thrombocytopenia in Hepato-Renal Failure and CVVHD

Pharmacist Specialist, Department of Pharmaceutical Services, University of California Davis Medical Center, Sacramento, CA; Clinical Professor of Pharmacy, School of Pharmacy, University of California at San Francisco, San Francisco, CA; Associate Clinical Professor of Medicine, University of California Davis School of Medicine, Sacramento

Richard H White, MD

Medical Director, Anticoagulation Service, University of California Davis Medical Center; Professor of Clinical Medicine, University of California Davis School of Medicine

Reprints: William E Dager PharmD FCSHP, Department of Pharmaceutical Services, University of California Davis Medical Center, 2315 Stockton Blvd., Sacramento, CA 95817-2201, FAX 916/703-4031, william.dager{at}ucdmc.ucdavis.edu

OBJECTIVE: To report a case of significant hepatic and renal failure with the use of argatroban in a patient with heparin-induced thrombocytopenia (HIT) requiring continuous veno-veno hemodialysis (CVVHD).

CASE SUMMARY: A 37-year-old Hispanic man with diabetes mellitus, ethanol abuse, and recent crank use developed a venous thrombosis and possible pulmonary embolism, followed by acute liver and renal failure requiring continuous veno-venous hemofiltration. After several days of heparin therapy, the dialyzer circuit thrombosed and the platelet count decreased to 82 x 10³/mm³. Antibodies for HIT by enzyme-linked immunosorbent assay were positive. Heparin was discontinued, and an argatroban infusion was initiated. After 39 hours on argatroban, the infusion was stopped when minor bleeding was observed with a concurrent activated partial thromboplastin time (aPTT) of 100 seconds. The dialyzer circuit did not clot during the argatroban infusion and did not apparently influence dose-related aPTT measurements. Several days were required for the aPTT to decrease after stopping the argatroban infusion. Fresh frozen plasma had no apparent effect on aPTT values.

DISCUSSION: Several different agents are currently available to provide effective anticoagulation in patients who have immune-mediated HIT. Argatroban is hepatically cleared and may be the preferred direct thrombin inhibitor in the presence of significant renal impairment, but conversely has prolonged effects in hepatic failure. Limited data are available regarding use of direct thrombin inhibitors in patients who have severe hepatic impairment with concurrent renal failure requiring CVVHD. Scant data are available regarding the effect of hemodialysis on the elimination of argatroban.

CONCLUSIONS: The optimal anticoagulant for use in a patient with HIT and concurrent hepatic and renal failure is unclear. No direct thrombin inhibitor has a proven advantage; therefore, selection may depend on clinical factors. Dosing in these patients requires very careful management.

Key Words: argatroban, heparin, hepatic failure, renal failure, thrombocytopenia

Published Online, July 17, 2003. www.theannals.com, DOI 10.1345/aph.1D010

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