LMWH Dosing for Pulmonary Embolism
For acute pulmonary embolism, use enoxaparin 1 mg/kg subcutaneously every 12 hours (or 1.5 mg/kg once daily for inpatients) for at least 5 days and until INR is 2.0-3.0 for 2 consecutive days when bridging to warfarin. 1
Standard Dosing Regimens
The European Society of Cardiology approves three LMWH options for PE treatment: 1
- Enoxaparin 1.0 mg/kg subcutaneously every 12 hours (preferred for most patients)
- Enoxaparin 1.5 mg/kg subcutaneously once daily (approved for inpatient treatment in the US and some European countries)
- Tinzaparin 175 U/kg subcutaneously once daily
Both enoxaparin regimens demonstrate equivalent efficacy and safety compared to unfractionated heparin, with recurrent VTE rates of 2.9-4.4% and major bleeding rates of 1.3-2.1%. 2, 3, 4, 5
Critical Dose Adjustments for Renal Impairment
For severe renal failure (CrCl <30 mL/min), reduce enoxaparin to 1 mg/kg once daily or switch to unfractionated heparin. 6, 7
- 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 7
- Enoxaparin clearance is reduced by 44% in severe renal impairment, leading to drug accumulation 7
- Unfractionated heparin is the preferred alternative in severe renal impairment: 80 U/kg IV bolus followed by 18 U/kg/hour infusion, adjusted to maintain aPTT 1.5-2.3 times control (46-70 seconds) 1, 6
- Fondaparinux is absolutely contraindicated when CrCl <30 mL/min 1, 7
Duration of Treatment
Continue LMWH for minimum 5 days regardless of INR, and do not stop until INR is 2.0-3.0 for at least 2 consecutive days. 1, 8
- Start warfarin on the same day as LMWH initiation, preferably within 24 hours 8
- The 5-day minimum 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, 8
- For cancer patients, extended LMWH monotherapy at 75-80% of initial dose for 6 months is superior to warfarin 8
Monitoring Requirements
Monitor platelet counts every 2-3 days from day 4 to day 14 to screen for heparin-induced thrombocytopenia (HIT). 1, 6
Anti-Xa level monitoring is not routinely required but should be considered in: 1
- Severe renal failure (CrCl <30 mL/min)
- Pregnancy
- Extreme body weights (<50 kg or >100 kg)
- 0.6-1.0 IU/mL for twice-daily dosing (measured 4 hours after morning injection)
- 1.0-2.0 IU/mL for once-daily dosing
Special Populations
Elderly Patients (≥75 years)
Avoid the initial 30 mg IV bolus of enoxaparin in patients ≥75 years due to increased bleeding risk. 7, 8 Use standard subcutaneous dosing with heightened vigilance for bleeding complications.
High-Risk PE (Shock/Hypotension)
Use intravenous unfractionated heparin rather than LMWH for hemodynamically unstable patients. 1, 8 LMWH has not been adequately tested in this population, and UFH allows for rapid reversal if needed.
Dialysis Patients
Administer enoxaparin 6-8 hours after hemodialysis completion to minimize bleeding risk at the vascular access site. 7 Consider switching to unfractionated heparin for better control in end-stage renal disease.
Common Pitfalls to Avoid
- Never stop LMWH before day 5, even if INR becomes therapeutic earlier 8
- Never stop LMWH until INR is 2.0-3.0 for 2 consecutive days, not just one measurement 1, 8
- Never switch between enoxaparin and UFH during the same hospitalization, as this increases bleeding risk 7
- Never use fondaparinux in severe renal impairment (CrCl <30 mL/min) 1, 7
- Never use standard dosing in severe renal impairment without dose adjustment 6, 7
Alternative: Direct Oral Anticoagulants
If using DOACs instead of warfarin: 8
- Rivaroxaban and apixaban can be started immediately without LMWH bridging
- Dabigatran and edoxaban require ≥5 days (ideally 3-5 days) of LMWH before switching 8, 9
Recent evidence suggests the optimal LMWH lead-in duration before DOACs is 3-5 days, as shorter durations (<3 days) are associated with higher mortality rates. 9