How to dose enoxaparin (low molecular weight heparin) in a patient with impaired renal function (eGFR 25ml/min) being treated for Acute Coronary Syndrome (ACS)?

Enoxaparin Dosing in ACS with Severe Renal Impairment (eGFR 25 mL/min)

For a patient with eGFR 25 mL/min presenting with acute coronary syndrome, reduce enoxaparin to 1 mg/kg subcutaneously once daily (not twice daily), which represents a 50% reduction in total daily dose compared to standard dosing. 1

Primary Dosing Recommendation

• Administer enoxaparin 1 mg/kg subcutaneously every 24 hours for patients with creatinine clearance <30 mL/min, as explicitly recommended by the American College of Cardiology for ACS management 1
• Do not give the initial 30 mg IV bolus that would normally be administered in younger patients with normal renal function 1
• This dose reduction is critical because enoxaparin clearance is reduced by 44% in severe renal impairment (CrCl <30 mL/min), leading to drug accumulation 2, 3

Pharmacokinetic Rationale

• Anti-Xa clearance decreases by 39% when CrCl falls below 30 mL/min, with drug exposure increasing by 35% after repeated dosing 4
• A strong linear correlation exists between creatinine clearance and enoxaparin clearance (R=0.85, P<0.001) 4
• Approximately 71% of enoxaparin is excreted unchanged renally, making accumulation inevitable in kidney failure 3
• Without dose adjustment, patients with CrCl <30 mL/min have 2.25 times higher odds of major bleeding (OR 2.25,95% CI 1.19-4.27) compared to those with normal renal function 4, 1

Alternative Anticoagulation Strategy

Consider switching to unfractionated heparin (UFH) as the preferred alternative, which does not require renal dose adjustment 5, 4:

• UFH dosing: 60 IU/kg IV bolus (maximum 4000 U) followed by 12 IU/kg/hour infusion (maximum 1000 U/hour) 4, 1
• Adjust infusion to maintain aPTT at 1.5-2.0 times control (60-80 seconds) 4, 1
• The European Society of Cardiology explicitly recommends UFH infusion adjusted to aPTT when CrCl is <30 mL/min 5

Contraindicated Alternatives

• Fondaparinux is absolutely contraindicated when CrCl <30 mL/min and should never be used 4, 1
• The European Society of Cardiology guidelines state fondaparinux should not be used when CrCl <20 mL/min 5

Monitoring Considerations

• Consider monitoring peak anti-Xa levels 4 hours after administration to prevent drug accumulation 4, 1
• Target therapeutic anti-Xa range is 0.5-1.0 IU/mL for once-daily dosing 4
• Routine monitoring is not required in most cases if the dose is appropriately adjusted 1

Critical Safety Warnings

• Never switch between enoxaparin and UFH once therapy is initiated, as this significantly increases bleeding risk 1, 4
• Avoid coadministration of medications that impair hemostasis (NSAIDs, antiplatelet agents beyond standard ACS therapy) when possible 6
• Elderly patients (≥75 years) with renal impairment represent a dual high-risk population requiring heightened vigilance for bleeding complications 4

Common Pitfalls to Avoid

• Do not use standard twice-daily dosing (1 mg/kg every 12 hours) in patients with CrCl <30 mL/min, as this increases major bleeding nearly 4-fold (8.3% vs 2.4%; OR 3.88) 4
• Do not rely on serum creatinine alone—always calculate creatinine clearance or eGFR, especially in elderly patients, women, and those with low body weight, as near-normal creatinine may mask severe renal dysfunction 5
• Do not assume moderate renal impairment (CrCl 30-60 mL/min) is safe with standard dosing—even this population shows increased bleeding risk (22% vs 5.7% major bleeding, OR 4.7) without dose adjustment 7

Clinical Decision Algorithm

1. Confirm renal function: Calculate CrCl using Cockcroft-Gault equation with ideal body weight 3
2. If CrCl <30 mL/min: Use enoxaparin 1 mg/kg SC once daily OR switch to UFH 5, 1
3. If CrCl 30-60 mL/min: Consider 25% dose reduction (to 0.75-0.8 mg/kg every 12 hours) based on emerging evidence of increased bleeding risk 4, 2, 7
4. If switching to UFH is chosen: Initiate UFH without overlap to avoid increased bleeding risk 1
5. Monitor closely: Assess for bleeding complications daily, particularly at vascular access sites 4