What is the recommended dosing of Enoxaparin (Low Molecular Weight Heparin) for Deep Vein Thrombosis (DVT) prevention in patients with varying risk factors, including acute coronary syndrome, impaired renal function, and obesity?

Enoxaparin Dosing for DVT Prophylaxis and Treatment

Standard Prophylactic Dosing

For DVT prophylaxis in hospitalized patients, administer enoxaparin 40 mg subcutaneously once daily, continuing for the duration of hospital stay or until fully ambulatory for medical patients, and at least 7-10 days for surgical patients. 1

• Enoxaparin offers superior bioavailability, longer half-life, more predictable anticoagulation, and lower risk of heparin-induced thrombocytopenia compared to unfractionated heparin 1
• An alternative prophylactic regimen of 30 mg subcutaneously every 12 hours has demonstrated superior efficacy in knee arthroplasty when started 12-24 hours post-surgery 1

Standard Therapeutic Dosing

For treatment of established DVT or pulmonary embolism, use enoxaparin 1 mg/kg subcutaneously every 12 hours as the preferred regimen, providing consistent therapeutic anticoagulation with proven efficacy equivalent to unfractionated heparin. 1, 2

• An alternative once-daily regimen of 1.5 mg/kg subcutaneously once daily is acceptable, though twice-daily dosing may provide more consistent anticoagulation 1, 3, 2
• Initial treatment typically lasts 5-10 days, overlapping with warfarin until INR >2.0 for 2 consecutive days 1
• For cancer-associated DVT, continue enoxaparin for at least 6 months and indefinitely while cancer remains active 1

---

Critical Dose Adjustments for Renal Impairment

Severe Renal Impairment (CrCl <30 mL/min)

In patients with severe renal impairment, reduce prophylactic enoxaparin to 30 mg subcutaneously once daily and therapeutic enoxaparin to 1 mg/kg subcutaneously once daily (a 50% total daily dose reduction). 1, 4, 3

• 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 4
• Therapeutic-dose enoxaparin without adjustment increases major bleeding nearly 4-fold (8.3% vs 2.4%; OR 3.88) 4
• Enoxaparin clearance is reduced by 44% in severe renal impairment, with drug exposure increasing by 35% after repeated dosing 4
• A strong linear correlation exists between CrCl and enoxaparin clearance (R=0.85, P<0.001) 4

Consider switching to unfractionated heparin as the preferred alternative in severe renal impairment, as it does not require renal dose adjustment. 4, 3

• UFH dosing: 60 U/kg IV bolus (maximum 4000 U) followed by 12 U/kg/hour infusion (maximum 1000 U/hour), adjusted to maintain aPTT at 1.5-2.0 times control (60-80 seconds) 4, 3

Moderate Renal Impairment (CrCl 30-60 mL/min)

For moderate renal impairment, reduce enoxaparin dose by 25% (to 75% of standard dose). 4, 3

• Enoxaparin clearance decreases by 31% in moderate renal impairment 4, 3
• Research shows 4.7-fold increased odds of major bleeding in patients with CrCl 30-50 mL/min receiving standard dosing 3

Monitoring in Renal Impairment

Monitor anti-Xa levels in all patients with CrCl <30 mL/min receiving prolonged enoxaparin therapy. 1, 4, 3

• Check peak anti-Xa levels 4 hours after administration, only after 3-4 doses have been given 1, 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: 0.5-1.5 IU/mL 1

Hemodialysis Patients

Administer enoxaparin 6-8 hours after hemodialysis completion to minimize bleeding risk at the vascular access site. 4

• Major bleeding rate is 6.8% in hospitalized hemodialysis patients, with highest risk at vascular access sites immediately post-dialysis 4
• Strongly consider switching to unfractionated heparin for therapeutic anticoagulation in dialysis patients, as it allows better control and does not accumulate 4

---

Obesity Dosing Adjustments

Moderate Obesity (BMI 30-40 kg/m²)

For prophylaxis in patients with BMI 30-40 kg/m², consider intermediate doses of 40 mg subcutaneously every 12 hours or weight-based dosing at 0.5 mg/kg subcutaneously every 12 hours. 1, 5

• Standard fixed dosing may be inadequate in obese patients 1
• Weight-based dosing at 0.5 mg/kg once daily results in peak anti-Xa levels within recommended prophylactic range (average 0.25 units/mL) without excessive anticoagulation 5

Severe Obesity (BMI ≥40 kg/m²)

For therapeutic anticoagulation in patients with BMI ≥40 kg/m², use 0.8 mg/kg subcutaneously every 12 hours. 1

• Use total body weight for dose calculation in obese patients 4

---

Special Population Considerations

Elderly Patients (≥75 years)

For acute coronary syndrome in patients ≥75 years, use 0.75 mg/kg subcutaneously every 12 hours without the initial 30 mg IV bolus. 4, 3

• Avoid the initial IV bolus due to increased bleeding risk 4
• Elderly patients have higher bleeding risk even with dose adjustment, especially when combined with renal impairment 4

Underweight Patients (<50 kg)

For underweight patients with severe renal impairment, use 30 mg subcutaneously once daily for prophylaxis, as both factors independently increase bleeding risk. 4, 3

• In patients weighing <45 kg with preserved renal function, consider reducing fixed-dose enoxaparin to 30 mg once daily 4

Pregnancy

For pregnant women with class III obesity requiring thromboprophylaxis, use intermediate doses of 0.5 mg/kg subcutaneously every 12 hours. 1

---

Acute Coronary Syndrome Dosing

For NSTEMI/STEMI, use enoxaparin 1 mg/kg subcutaneously every 12 hours, with bridging for a minimum of 48 hours, preferably for the duration of hospitalization (up to 8 days) or until revascularization. 4

• An initial IV loading dose of 30 mg may be used in selected patients with normal renal function 4
• Continue bridging until therapeutic INR is achieved if transitioning to warfarin 4

---

Critical Safety Considerations and Contraindications

Fondaparinux Contraindication

Fondaparinux is absolutely contraindicated when CrCl <30 mL/min and should never be used in dialysis patients. 4, 3

Timing with Neuraxial Anesthesia

Avoid enoxaparin administration within 10-12 hours before neuraxial anesthesia to prevent spinal hematoma. 1

• For prophylactic doses after neuraxial anesthesia, enoxaparin may be started as early as 4 hours after catheter removal but not earlier than 12 hours after the block was performed 1

Anticoagulant Switching

Never switch between enoxaparin and unfractionated heparin mid-treatment, as this significantly increases bleeding risk. 4, 3

Heparin-Induced Thrombocytopenia

Monitor platelet counts every 2-3 days from day 4 to day 14 to screen for heparin-induced thrombocytopenia. 1, 4

• Avoid enoxaparin in patients with active heparin-induced thrombocytopenia; use direct thrombin inhibitors or fondaparinux instead (if renal function permits) 3

---

Hepatic Impairment

Enoxaparin is primarily eliminated renally, not hepatically, making it safer than unfractionated heparin in patients with liver dysfunction. 1

• Elevated transaminases (ALT/AST) without coagulopathy or synthetic dysfunction do not contraindicate enoxaparin use 1
• Avoid enoxaparin in patients with moderate-to-severe liver disease or hepatic coagulopathy 1
• Elevated liver enzymes alone do not require dose adjustment 1

---

Duration of Therapy

For provoked DVT, treat for exactly 3 months; for unprovoked DVT or cancer-associated DVT, treat for a minimum of 3-6 months initially, then continue indefinitely. 1

• For cancer-associated DVT, continue enoxaparin for at least 6 months and indefinitely while cancer remains active or under treatment 1
• For symptomatic catheter-associated DVT, treat for at least 3 months or as long as the catheter remains in place 1