What is the recommended dose of low molecular weight heparin (LMWH), such as enoxaparin, for the treatment of pulmonary embolism (PE)?

Enoxaparin Dosing for Pulmonary Embolism

For acute PE treatment, administer enoxaparin 1 mg/kg subcutaneously every 12 hours (twice daily) or 1.5 mg/kg subcutaneously once daily, continuing for a minimum of 5 days and until INR reaches 2.0-3.0 for two consecutive days when bridging to warfarin. 1

Standard Therapeutic Dosing

Two FDA-approved regimens exist for PE treatment: 1

• 1 mg/kg subcutaneously every 12 hours (twice daily) - the most widely validated regimen 2
• 1.5 mg/kg subcutaneously once daily - approved for inpatient treatment in the US and some European countries 1

Both regimens demonstrate equivalent efficacy and safety in clinical trials comparing LMWH to unfractionated heparin for acute PE 3, 4, 5

Duration and Bridging Strategy

Minimum treatment duration is 5 days regardless of INR response 1

• Start warfarin on the same day as enoxaparin initiation, preferably within 24 hours 1
• Continue enoxaparin until INR is 2.0-3.0 for two consecutive days 1
• Do not discontinue enoxaparin before day 5 even if INR becomes therapeutic earlier 1

This approach is based on randomized trials showing 5-7 days of heparin is as effective as 10-14 days when followed by adequate oral anticoagulation 1

Critical Dose Adjustments for Renal Impairment

For severe renal insufficiency (creatinine clearance <30 mL/min), reduce enoxaparin to 1 mg/kg subcutaneously every 24 hours (once daily) 2

• Enoxaparin accumulates in renal failure, with renal clearance reduced by 31% in moderate impairment (CrCl 30-60 mL/min) and 44% in severe impairment (CrCl <30 mL/min) 2
• Standard unadjusted doses carry a 2- to 3-fold increased bleeding risk in severe renal insufficiency 2
• Consider unfractionated heparin with aPTT monitoring as an alternative in severe renal failure 1

Special Populations and Contraindications

Do not use enoxaparin in hemodynamically unstable PE (shock or hypotension) 1

• Use intravenous unfractionated heparin instead, as LMWH has not been tested in unstable patients 1

For cancer patients requiring extended anticoagulation: 1

• Continue LMWH at 75-80% of initial dose for 6 months rather than switching to warfarin 2, 1
• Extended LMWH monotherapy is superior to warfarin in cancer-associated VTE 1
• Continue anticoagulation as long as active malignancy persists 1

Key Clinical Pitfalls to Avoid

Common errors that increase morbidity: 1

• Stopping enoxaparin before day 5 of treatment
• Discontinuing enoxaparin when INR first becomes therapeutic (must be therapeutic for 2 consecutive days)
• Failing to monitor platelet counts every 2-3 days from day 4 to day 14 to screen for heparin-induced thrombocytopenia 1
• Using warfarin as first-line in cancer patients instead of extended LMWH 1

Alternative: Direct Oral Anticoagulants

If using DOACs instead of warfarin: 2

• Dabigatran and edoxaban require ≥5 days of enoxaparin before switching 1
• Rivaroxaban and apixaban can be started immediately without LMWH bridging 1
• DOACs demonstrate non-inferiority to LMWH/warfarin with similar bleeding rates 2