Argatroban anticoagulation in patients with heparin-induced thrombocytopenia requiring renal replacement therapy.

Abstract

BACKGROUND:

Argatroban, a direct thrombin inhibitor, is used for prophylaxis or treatment of thrombosis in heparin-induced thrombocytopenia (HIT). The recommended initial dose is 2 microg/kg/min (0.5 microg/kg/min in hepatic impairment), adjusted to achieve activated partial thromboplastin time (aPTT) values 1.5-3.0 times baseline. However, few argatroban-treated patients with HIT and renal failure requiring renal replacement therapy (RRT) have been described.

OBJECTIVE:

To evaluate the safety and efficacy of argatroban anticoagulation during RRT in patients with HIT.

METHODS:

We retrospectively reviewed records from 47 patients with HIT and renal failure requiring RRT who underwent 50 treatment courses with argatroban. Patients with HIT had received argatroban during prospective, multicenter studies. Outcomes, safety, and dosing information were summarized.

RESULTS:

In the multicenter experience, no patient died due to thrombosis and 2 (4%) patients developed new thrombosis while on argatroban. No adverse outcomes occurred during argatroban reexposure. Starting doses were typically 2 microg/kg/min in patients without hepatic impairment and <1.5 microg/kg/min in those with hepatic impairment. Median (range) infusion doses were 1.7 (0.2-2.8) and 0.7 (0.1-1.7) microg/kg/min, respectively, with associated median (range) aPTT ratios, relative to baseline, of 2.2 (1.6-3.6) and 2.0 (1.4-4.1), respectively. Major bleeding occurred in 3 (6%) of 50 treatment courses.

CONCLUSIONS:

Argatroban provides effective anticoagulation upon initial and repeated administration in patients with HIT and renal impairment requiring RRT, with an acceptably low bleeding risk. Current dosing recommendations are adequate for these patients.

• Authors: Bharathi V Reddy, Eric J Grossman, Sharon A Trevino, Marcie J Hursting, Patrick T Murray
• Journal: The Annals of pharmacotherapy (Ann Pharmacother) Vol. 39 Issue 10 Pg. 1601-5 (Oct 2005) ISSN: 1060-0280 [Print] United States
• PMID: 16131539 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Pipecolic Acids
• Sulfonamides
• Heparin
• Arginine
• argatroban

Topics

• Acute Kidney Injury (blood, therapy)
• Adult
• Aged
• Aged, 80 and over
• Anticoagulants (administration & dosage, adverse effects, therapeutic use)
• Arginine (analogs & derivatives)
• Drug Administration Schedule
• Female
• Heparin (administration & dosage, adverse effects, therapeutic use)
• Humans
• Kidney Failure, Chronic (blood, therapy)
• Male
• Middle Aged
• Pipecolic Acids (administration & dosage, adverse effects, therapeutic use)
• Prospective Studies
• Renal Replacement Therapy (methods)
• Retrospective Studies
• Sulfonamides
• Thrombocytopenia (blood, chemically induced, drug therapy)
• Treatment Outcome