Duration of Heparin Therapy for Pulmonary Embolism
Unfractionated heparin should be continued for a minimum of 5 days and discontinued only after warfarin achieves a therapeutic INR of 2.0-3.0 for at least 2 consecutive days. 1
Initial Heparin Dosing and Monitoring
- Start with a bolus of 5,000-10,000 IU (or 80 IU/kg weight-adjusted) followed by continuous infusion of 1,300 IU/hour (or 18 IU/kg/hour weight-adjusted) to achieve rapid therapeutic anticoagulation 1
- Adjust the infusion rate to maintain aPTT at 1.5-2.5 times control (45-75 seconds) 1
- Check aPTT 4-6 hours after the initial bolus, then 6-10 hours after any dose adjustment, and daily once therapeutic 1
Mandatory Minimum Duration: The 5-Day Rule
The critical principle is that heparin must continue for at least 5 days regardless of how quickly the INR becomes therapeutic. 1, 2 This is based on evidence showing that shorter durations (4-6 weeks) result in increased recurrence rates compared to the standard 3-6 month duration. 1
Overlapping with Warfarin
- Start warfarin on the same day as heparin initiation (5-10 mg daily for 2 days) 1
- Continue heparin for the full 5 days even if INR reaches 2.0-3.0 earlier 1, 2
- Only discontinue heparin after BOTH conditions are met: (1) at least 5 days have passed AND (2) INR is 2.0-3.0 for 2 consecutive days 1, 2
Special Circumstances Requiring Longer Heparin Duration
High-Risk PE (Hemodynamic Instability)
- Use unfractionated heparin rather than LMWH in patients with shock or persistent hypotension 1, 2
- Continue UFH until hemodynamic stability is achieved before transitioning to oral anticoagulation 1
Severe Renal Dysfunction
- In patients with creatinine clearance <30 mL/min, use UFH with aPTT monitoring rather than LMWH due to accumulation risk 2
- UFH allows for more precise dose adjustment and rapid reversal if needed 1
Post-Thrombolysis
- After thrombolytic therapy, resume heparin at maintenance dose (without bolus) once aPTT falls below 2 times the upper limit of normal 1
Critical Pitfalls to Avoid
- Never stop heparin before day 5, even if INR is therapeutic - this is associated with increased recurrence risk 2
- Never stop heparin until INR is therapeutic for 2 consecutive days - a single therapeutic INR is insufficient 1, 2
- Monitor platelet counts every 2-3 days from day 4 to day 14 to screen for heparin-induced thrombocytopenia 2
- Avoid extending heparin beyond 5-7 days unless warfarin transition is problematic, as prolonged heparin increases bleeding risk without additional benefit 1
Alternative: LMWH Instead of UFH
For most non-high-risk PE patients, LMWH (enoxaparin 1 mg/kg SC every 12 hours or 1.5 mg/kg once daily) is preferred over UFH due to equal efficacy, improved safety profile, and ease of use 1, 2. The same 5-day minimum duration and INR overlap requirements apply to LMWH. 1, 2