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Jeff Nagge, BScPhm,BSc; Mark Crowther, MD,MSc; Jack Hirsh, MD,FCCP

Arch Intern Med. 2002;162:2605-2609.

Background  Because of the risk of accumulation of anticoagulant effect, it has been suggested that patients with a creatinine clearance of 30 mL/min or less (0.50 mL/s) should be excluded from treatment with low-molecular-weight (LMW) heparin, or have anti–factor Xa heparin level monitoring performed.

Objective  To assess the appropriateness of this recommendation.

Methods  We performed a systematic search of MEDLINE, EMBASE, and International Pharmaceutical Abstracts to identify prospective articles comparing differences in the pharmacokinetics of LMW heparins in nondialyzed patients with varying degrees of renal function. Reference lists of retrieved reports were checked for additional articles.

Results  Three single-dose pharmacokinetic trials and 2 multiple-dose deep vein thrombosis (treatment trials met our selection criteria. The 3 trials that could address our primary objective did not support the use of a 30-mL/min (0.50-mL/s) cutoff of creatinine clearance to select individuals at risk of accumulation when LMW heparin is used. Four of the 5 trials support the notion that anti–factor Xa activity of some LMW heparin preparations accumulates in patients with impaired creatinine clearance. Tinzaparin sodium, an LMW heparin with a higher-than-average molecular weight distribution, appears to be the exception, since it did not exhibit accumulation in patients with creatinine clearances as low as 20 mL/min (0.33 mL/s).

Conclusions  The use of a 30-mL/min (0.50-mL/s) cutoff is not justified, on the basis of currently available evidence, to select individuals at increased risk of accumulation when LMW heparin is used. The pharmacokinetic response to impaired renal function may differ among LMW heparin preparations.

From the Department of Pharmacy, Hamilton Health Sciences, Hamilton, Ontario (Mr Nagge); Department of Medicine, St Joseph's Hospital, Hamilton (Dr Crowther); and Hamilton Civic Hospital Research Center (Dr Hirsh). Mr Nagge is now with the Department of Pharmacy, University Health Network, Toronto General Hospital, Toronto, Ontario.

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