Dose reduction of LMWH (enoxaparin) in chronic kidney disease

Although Low Molecular Weight Heparins (LMWH) are a convenient and effective alternative to unfractionated heparins, it is important to remember that LMWH such as enoxaparin (Indian Brands Clexane, Lomonox and LMWX) also have associated risks. LMWH have a longer half life than unfractionated heparins, their anticoagulant effect is not routinely monitored, and their effects are harder to reverse in cases of bleeding. The clearance of enoxaparin is decreased in chronic kidney disease, hence the dose of enoxaparin should be reduced in this situation.¹

In 2005-2006, ADRAC received 10 reports of death associated with haemorrhage after the use of enoxaparin, bringing the total to 46 since 1997. In 3 of the reports received in 2005, patients with chronic kidney disease received inappropriate doses. Two of the reports also implicated an incorrect dose for the weight of the patient. Other risk factors include use of other anticoagulants, age (neonates, children, and the elderly), pregnancy and the extremes of body weight (< 40 kg or > 100 kg).^2,3

Before commencement of LMWH therapy, the patient's renal function should be assessed. In patients with severe chronic kidney disease (GFR < 30 mL/min), requiring therapeutic anticoagulant doses, the dose of enoxaparin should be reduced from 1 mg/kg twice daily or 1.5 mg/kg once daily to 1 mg/kg once daily.¹ An alternative is to use unfractionated heparin with dose monitoring by aPTT. Similarly, in patients with unstable or deteriorating renal function, unfractionated heparin is preferred. Where there is a high bleeding risk, such as in the post-operative period, unfractionated heparin is preferred, since rapid and complete reversal of anticoagulation can be achieved. If there is a high probability of proceeding to surgery in the next 5 days (including for coronary angioplasty), unfractionated heparin with the usual aPTT monitoring is advised.

Reference

1. Clexane Product Information June 2005. Aventis Pharma Pty Limited. MIMS On-line.
2. Eikelboom JW, Hankey J. Low molecular weight heparins and heparinoids. Med J Aust 2002;177:379-383.
3. Heparin contraindicated in severe renal impairment. WHO Drug Information 2005;19:24-25.

Reference
Australian Adverse Drug Reactions Bulletin, Volume 25, Number 4, August 2006