December 9, 2002Archives of Internal Medicine141 citations
View Full PaperIs Impaired Renal Function a Contraindication to the Use of Low-Molecular-Weight Heparin?
Key Result
A systematic review of 5 trials found that a 30-mL/min creatinine clearance cutoff is not justified to select individuals at increased risk of accumulation when low-molecular-weight heparin is used.
Key Points
- To evaluate whether impaired renal function is a contraindication for low-molecular-weight heparin use.
- Conducted a systematic search of MEDLINE, EMBASE, and International Pharmaceutical Abstracts.
- Identified prospective articles comparing pharmacokinetics of low-molecular-weight heparins in nondialyzed patients.
- Reviewed reference lists for additional studies.
- Three trials did not support a 30 mL/min creatinine clearance cutoff for LMW heparin usage.
- Four out of five trials indicated risk of accumulation of anti-factor Xa activity in patients with impaired renal function.
- Tinzaparin sodium did not show accumulation in patients with creatinine clearance as low as 20 mL/min.
Study Design
Type
Systematic Review
Structured PICO
Does impaired renal function contraindicate the use of low-molecular-weight heparin in nondialyzed patients?
P
Population
Systematic review of 5 trials assessing the pharmacokinetics of low-molecular-weight heparins in nondialyzed patients with varying degrees of renal function.
I
Intervention
Low-molecular-weight (LMW) heparin preparations (including tinzaparin sodium)
C
Comparator
Patients with different degrees of renal function
O
Outcome
Pharmacokinetics of LMW heparins (accumulation of anti-factor Xa activity)surrogate
A 30-mL/min creatinine clearance cutoff is not justified as a universal contraindication for LMW heparins, as pharmacokinetic responses vary among preparations, with tinzaparin showing no accumulation down to 20 mL/min.
Abstract
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 (< or =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.