Bilateral PE Heparin Protocol
For bilateral pulmonary embolism, initiate unfractionated heparin immediately with an 80 U/kg IV bolus followed by continuous infusion at 18 U/kg/hour, then adjust based on aPTT monitoring to maintain therapeutic range of 1.5-2.3 times control (46-70 seconds). 1
Immediate Initiation
- Start heparin immediately when PE is suspected—do not wait for diagnostic confirmation in patients with intermediate or high clinical probability, as untreated PE carries high mortality risk and early therapeutic anticoagulation prevents recurrent thromboembolism 1, 2
- The weight-based dosing regimen is superior to fixed dosing and achieves therapeutic anticoagulation more rapidly 1, 3
Initial Dosing Protocol
Weight-Based Regimen (Preferred):
Alternative Fixed-Dose Regimen (if weight unavailable):
aPTT Monitoring and Adjustment
- Check first aPTT 4-6 hours after initiating heparin 1, 3
- Target aPTT: 1.5-2.3 times control (typically 46-70 seconds) 1, 3
- Subtherapeutic anticoagulation in the first 24 hours increases recurrence rates significantly 1
Dose Adjustment Nomogram
| aPTT Result | Action |
|---|---|
| <35 seconds (<1.2× control) | Give 80 U/kg bolus; increase infusion by 4 U/kg/h [1] |
| 35-45 seconds (1.2-1.5× control) | Give 40 U/kg bolus; increase infusion by 2 U/kg/h [1] |
| 46-70 seconds (1.5-2.3× control) | No change - therapeutic range [1] |
| 71-90 seconds (2.3-3.0× control) | Decrease infusion by 2 U/kg/h [1] |
| >90 seconds (>3.0× control) | Stop infusion for 1 hour, then decrease by 3 U/kg/h [1] |
Duration and Transition to Oral Anticoagulation
- Continue heparin for at least 5 days AND until INR ≥2.0 for at least 24 hours on two consecutive measurements 1, 3
- Start warfarin simultaneously with heparin at 5-10 mg daily for first 2 days 1, 2
- Target INR: 2.0-3.0 throughout treatment 1, 2
- Never stop heparin before INR is therapeutic for 24 hours—this creates a dangerous gap in anticoagulation 1, 2
Special Considerations for Bilateral PE
- For hemodynamically unstable patients with bilateral PE, use continuous IV unfractionated heparin for predictable anticoagulation—avoid subcutaneous heparin in massive PE 1
- Consider thrombolytic therapy immediately if hemodynamically unstable, stopping heparin before thrombolysis and resuming at maintenance dose after completion 2
- Bedside echocardiography should be performed immediately in hemodynamically unstable patients to assess right ventricular function 2
Alternative Agents for Stable Patients
For hemodynamically stable patients with bilateral PE, low molecular weight heparin or fondaparinux are acceptable alternatives 1, 4, 5:
- Enoxaparin: 1.0 mg/kg subcutaneously every 12 hours OR 1.5 mg/kg once daily 1
- Tinzaparin: 175 U/kg subcutaneously once daily 1
- Fondaparinux: Weight-adjusted (5 mg if <50 kg, 7.5 mg if 50-100 kg, 10 mg if >100 kg) subcutaneously once daily 1
Critical Pitfalls to Avoid
- Never use fixed-dose heparin without weight adjustment—this leads to delayed achievement of therapeutic anticoagulation and increases recurrence risk 1
- Never delay heparin while awaiting diagnostic tests in patients with suspected PE 1, 2
- Never discontinue heparin before INR is therapeutic for 24 hours—this creates a gap in anticoagulation 1, 2
- Avoid subcutaneous heparin in massive or bilateral PE—use continuous IV infusion for predictable anticoagulation 1
Laboratory Monitoring
- Monitor platelet counts every 2-3 days from day 4 to day 14 to screen for heparin-induced thrombocytopenia (HIT), which occurs in up to 5% of patients receiving unfractionated heparin 3
- Each facility should calibrate their aPTT range to correspond to anti-Xa activity of 0.3-0.6 IU/mL, as aPTT reagents vary between laboratories 1
- In cases of heparin resistance (aPTT not responding to appropriate doses), measure anti-Xa levels directly 1