What is the dose of Clexane (enoxaparin) for therapeutic and prophylactic anticoagulation in patients with varying renal function and body weight?

Enoxaparin (Clexane) Dosing for Therapeutic and Prophylactic Anticoagulation

For prophylaxis, use 40 mg subcutaneously once daily in patients with normal renal function, but reduce to 30 mg once daily when creatinine clearance falls below 30 mL/min; for therapeutic anticoagulation, use 1 mg/kg subcutaneously every 12 hours with normal renal function, but reduce to 1 mg/kg once daily when CrCl <30 mL/min. 1, 2, 3

Standard Prophylactic Dosing

Normal Renal Function (CrCl >30 mL/min)

• Standard dose: 40 mg subcutaneously once daily for venous thromboembolism prophylaxis in hospitalized medical patients 4, 1, 3
• This dosing applies to most hospitalized non-critically ill patients at risk for VTE 4
• Once-daily regimens are preferred to reduce healthcare worker exposure 4

Severe Renal Impairment (CrCl <30 mL/min)

• Reduce to 30 mg subcutaneously once daily - this is the only FDA-approved prophylactic dose adjustment among all low-molecular-weight heparins for severe renal impairment 1, 2, 3
• This dose reduction is critical because enoxaparin clearance decreases by 44% in severe renal impairment, leading to a 2-3 fold increased bleeding risk without dose adjustment 1, 2
• The renal impairment takes absolute priority over weight-based adjustments - do not increase above 30 mg daily regardless of body weight 1

Special Populations for Prophylaxis

• Critically ill patients with normal renal function: Consider intensified prophylaxis with 40 mg twice daily based on expert opinion, though this remains controversial 4
• Obese patients: Consider 50% dose increase (e.g., 60 mg daily) in patients with extremes of body weight 4
• Underweight patients (<55 kg) with severe renal impairment: Use 30 mg once daily, as both factors independently increase bleeding risk 2

Standard Therapeutic Dosing

Normal Renal Function (CrCl >30 mL/min)

• Standard dose: 1 mg/kg subcutaneously every 12 hours for treatment of venous thromboembolism or acute coronary syndrome 1, 3, 5
• Alternative once-daily regimen: 1.5 mg/kg subcutaneously once daily, though twice-daily dosing may be more efficacious 3, 5
• For acute coronary syndrome in patients <75 years: May add initial 30 mg IV bolus followed by 1 mg/kg subcutaneously every 12 hours 1, 6

Moderate Renal Impairment (CrCl 30-50 mL/min)

• Consider dose reduction to 0.8 mg/kg every 12 hours after the first full dose, as enoxaparin clearance decreases by 31% in moderate renal impairment 1, 3
• Some guidelines recommend 25% dose reduction (to 75% of standard dose) 2

Severe Renal Impairment (CrCl <30 mL/min)

• Reduce to 1 mg/kg subcutaneously once daily (a 50% total daily dose reduction) 1, 2, 3
• This adjustment is mandatory - patients with CrCl <30 mL/min have 2.25 times higher odds of major bleeding (OR 2.25,95% CI 1.19-4.27) with standard dosing 2
• Unadjusted therapeutic dosing increases major bleeding risk nearly 4-fold (8.3% vs 2.4%) 2

Elderly Patients (≥75 years)

• For acute coronary syndrome: Use 0.75 mg/kg subcutaneously every 12 hours without IV bolus, regardless of renal function 1, 3, 6
• Avoid the initial 30 mg IV bolus due to increased bleeding risk 2, 6
• Exercise extreme caution when combining advanced age with renal insufficiency - these are dual high-risk factors 2

Critical Safety Considerations and Monitoring

When to Monitor Anti-Xa Levels

• Monitor in all patients with CrCl <30 mL/min receiving prolonged treatment 1, 2, 3
• Check peak anti-Xa levels 4 hours after administration, only after 3-4 doses have been given 1, 2, 3
• Target therapeutic anti-Xa range: 0.5-1.0 IU/mL for twice-daily dosing, >1.0 IU/mL for once-daily dosing 1, 3
• Target prophylactic anti-Xa range: 0.29-0.34 IU/mL 1

Absolute Contraindications and Precautions

• Fondaparinux is absolutely contraindicated when CrCl <30 mL/min - never use in dialysis patients 2, 3
• Never switch between enoxaparin and unfractionated heparin mid-treatment - this significantly increases bleeding risk 1, 2, 3
• Avoid enoxaparin within 10-12 hours of neuraxial anesthesia to prevent spinal hematoma 1

Alternative Anticoagulation Strategy

When to Switch to Unfractionated Heparin

• For severe renal impairment (CrCl <30 mL/min) requiring therapeutic anticoagulation, strongly consider switching to unfractionated heparin 1, 2, 3
• UFH is the preferred alternative because it undergoes reticuloendothelial clearance, not renal, and does not accumulate in renal failure 1, 2
• UFH dosing: 60 IU/kg IV bolus (maximum 4000 U) followed by 12 IU/kg/hour infusion (maximum 1000 U/hour), adjusted to maintain aPTT at 1.5-2.0 times control (60-80 seconds) 1, 2, 3

Special Consideration for Hemodialysis Patients

• Administer enoxaparin 6-8 hours after hemodialysis completion to minimize bleeding risk at the vascular access site 2
• For hemodialysis anticoagulation during the dialysis session itself, research suggests an initial dose of 0.70 mg/kg (equivalent to 70 IU/kg) 7
• Consider switching to UFH for systemic anticoagulation in end-stage renal disease patients requiring ongoing therapeutic anticoagulation 2

Common Pitfalls to Avoid

• Failing to calculate creatinine clearance in elderly, women, or low body weight patients - near-normal serum creatinine may mask severely reduced CrCl 2
• Using standard dosing in severe renal impairment - this leads to dangerous drug accumulation with anti-Xa clearance reduced by 39% and drug exposure increased by 35% with repeated dosing 2
• Combining enoxaparin with additional UFH at time of PCI - this increases bleeding without improving outcomes 1
• Ignoring the strong linear correlation between CrCl and enoxaparin clearance (R=0.85, P<0.001) - always dose-adjust based on renal function 2