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Semin Thromb Hemost 2002; 28(5): 467-482
DOI: 10.1055/s-2002-35288
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Hirudin In Renal Insufficiency

Karl-Georg Fischer
  • University Hospital Freiburg, Department of Medicine, Division of Nephrology and General Medicine, Freiburg, Germany
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Publication History

Publication Date:
06 November 2002 (online)

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ABSTRACT

Recombinant hirudins (r-hirudins) are potent direct thrombin inhibitors increasingly used for alternative anticoagulation, especially in heparin-induced thrombocytopenia. R-hirudins are almost exclusively eliminated by the kidneys, and a close correlation between r-hirudin clearance and endogenous creatinine clearance has been observed. Accordingly, the pharmacokinetics of r-hirudin are altered in patients with renal insufficiency. A decline of renal r-hirudin clearance is associated with an increase of r-hirudin half-life and the area under the curve (AUC). Therefore, renal impairment necessitates reduction of r-hirudin dose to avoid overdose or inadequate accumulation of the thrombin inhibitor. To this end, close monitoring of r-hirudin anticoagulation is required, which at best is performed by measuring r-hirudin blood levels by ecarin clotting times (ECT) or chromogenic assays, in addition to activated partial thromboplastin time (aPTT). Recent studies showed that r-hirudin anticoagulation is feasible in acute or chronic renal failure treated with continuous or intermittent renal replacement therapy, if appropriate r-hirudin dosing and adequate monitoring are warranted. High-volume hemofiltration with r-hirudin-permeable hemodialyzers constitutes a valuable means to markedly reduce r-hirudin blood concentration and total r-hirudin body content in case of r-hirudin overdose or r-hirudin-associated bleeding. In the future, the hepatically eliminated direct thrombin inhibitor argatroban may facilitate alternative anticoagulation in patients with renal insufficiency.

KEYWORDS

Recombinant hirudin - renal insufficiency - pharmacokinetics - hemodialysis - dosing

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