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Electronic letters published:
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Low-Molecular-Weight Heparin And Bleeding in Patients with Severe Renal Insufficiency
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T. S. Dharmarajan, MD, FACP, AGSF Our Lady of Mercy Medical Center, Amit Sohagia, MD
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asohagia1204{at}yahoo.com T. S. Dharmarajan, et al.
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To the Editor, We read with interest the significant information provided in the meta-analysis published recently in the Annals (1) suggesting that patients with severe renal insufficiency on standard doses of enoxaparin have an increased risk for major bleeding, perhaps attributable to elevated levels of Anti-Xa (1). The presence of renal impairment causes a delay in the elimination of enoxaparin; in fact, a linear relationship between anti-factor Xa plasma clearance and steady-state creatinine clearance correlates with decline in enoxaparin clearance and resultant increased anticoagulant activity (2). While the authors and others recommend a reduction in enoxaparin dosage with a creatinine clearance lower than 30 ml/min, pharmacokinetic analysis of anti-Xa activity suggests alterations even in the presence of mild to moderate renal impairment, i.e. even with creatinine clearance lower than 50 mL/min (3). Further, it is recognized that age related sarcopenia and a decline in creatinie clearance (age or disease related) contribute to errors in interpretation of serum creatinine alone; while creatinine clearance can be determined by using the Cockroft-Gault formula or the MDRD (Modification of Diet in Renal Disease calculator), neither formula has been considered perfect, and the preferred method is controversial (4). Predictions from the formulae also show weak but positive correlations with percentage body fat. Enoxaparin clearance also depends on body weight. Thus enoxaparin dosing ultimately should take into consideration alterations in renal function (including from age), body weight (plus fat distribution), gender and anti-Xa activity in steady state (5). Attention to concomitant medication use is worthwhile. We are presently in an era where the use of low-molecular weight heparin in healthcare is on the increase, in view of greater awareness to institute measures for thrombo-embolic prophylaxis and treatment. So how do we lower risk of bleeding, but maintain benefit? Perhaps we can educate providers on considerations pertinent to low molecular heparin. The following list provides a start: (1) Enhance awareness of pharmacokinetics; (2) Age and gender considerations; (3) Ideal body weight and fat distribution; (4) Anti-Xa activity: measurement; (5) Calculate GFR, do not dose solely based on serum creatinine; (6) Adjust dose to graded renal function (rather than creatinine clearance < 30 or >30 ml/min) and body weight; and (7) Consider drug-drug interactions e.g. anti -platelet agents. T.S. Dharmarajan MD, FACP, AGSF Chairman, Department of Medicine Our Lady of Mercy Medical Center Bronx, New York Professor of Medicine, New York Medical College, Valhalla, NY Amit Sohagia MD Senior Resident in Medicine Our Lady of Mercy Medical Center Bronx, New York 10466 asohagia1204@yahoo.com References: 1.Lim W, Dentali F, Eikelboom JW, Crowther MA. Meta-analysis: low- molecular-weight heparin and bleeding in patients with severe renal insufficiency. Annals of Internal Medicine 2006; 144(9): 673-84. 2.Chow SL, Zammit K, West K et al. Correlation of antifactor Xa concentrations with renal function in patients on enoxaparin. Journal of Clinical Pharmacology.2003; 43(6): 586-90. 3.Hulot JS, Montalescot G, Lechat P et al. Dosing strategy in patients with renal failure receiving enoxaparin for the treatment of non-St-segment elevation acute coronary syndrome. Clin Pharmacol. 2005; 77(6): 542-52 4.Poggio ED, Hall PM. Estimation of glomerular filtraion rate by creatinine-based formulas: Any room for improvement (editorial). NephSAP. 2006; 5(3): 131-140. 5.Hulot JS, Nantelon C, Urien S, et al. Effect of renal function on the pharmacokinetics of enoxaparin and consequences on dose adjustment. Therapeutic Drug Monitoring. 2004 Jun; 26(3): 305-10. Conflict of Interest:None declared |
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