Heparin Infusion Protocol for Pulmonary Embolism
For patients with acute pulmonary embolism, initiate unfractionated heparin with an 80 U/kg intravenous bolus followed by continuous infusion at 18 U/kg/h, then adjust based on aPTT monitoring using a weight-based nomogram to maintain aPTT at 1.5-2.3 times control (46-70 seconds). 1
Initial Dosing Regimen
Weight-based dosing is superior to fixed dosing and should be the standard approach for all patients with pulmonary embolism 1, 2:
- Initial bolus: 80 U/kg intravenous push 1
- Continuous infusion: 18 U/kg/h 1
- Alternative fixed-dose regimen (if weight-based unavailable): 5,000-10,000 U bolus followed by 1,250-1,300 U/h infusion 1
aPTT Monitoring and Dose Adjustment
Check the first aPTT 4-6 hours after initiating heparin infusion, then adjust according to the following nomogram 1, 2:
| 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] |
- Target aPTT: 1.5-2.3 times control (typically 46-70 seconds) 1, 2
- Continue monitoring aPTT approximately every 4 hours until stable in therapeutic range, then at appropriate intervals 2
Critical Timing Considerations
Start heparin immediately when pulmonary embolism is suspected - do not wait for diagnostic confirmation in patients with intermediate or high clinical probability 1, 3. This is particularly important because:
- Untreated PE carries high mortality risk 1
- Early therapeutic anticoagulation prevents recurrent thromboembolism 1
- Subtherapeutic anticoagulation in the first 24 hours is associated with increased recurrence rates 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 4, 3
- Start warfarin simultaneously with heparin at 5-10 mg daily for first 2 days 4, 3
- Target INR: 2.0-3.0 throughout treatment 4, 3
- Do not discontinue heparin prematurely before adequate oral anticoagulation is achieved 3, 5
Special Populations and Alternative Agents
For hemodynamically stable patients, low molecular weight heparin (LMWH) or fondaparinux are acceptable alternatives 1:
- 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, 6
For massive PE with hemodynamic instability, unfractionated heparin remains the preferred agent because LMWH trials excluded these high-risk patients 1.
Essential Safety Monitoring
Throughout heparin therapy, monitor 2:
- Platelet count at baseline and periodically (to detect heparin-induced thrombocytopenia) 2
- Hematocrit periodically 2
- Occult blood in stool periodically 2
Common Pitfalls to Avoid
- Never use fixed-dose heparin without weight adjustment - this leads to delayed achievement of therapeutic anticoagulation 1
- Never delay heparin while awaiting diagnostic tests in patients with suspected PE 1, 3
- Never stop heparin before INR is therapeutic for 24 hours - this creates a gap in anticoagulation 4, 3
- Never use intramuscular route - high risk of hematoma formation 2
- Avoid subcutaneous heparin in massive PE - use continuous IV infusion for predictable anticoagulation 1
Laboratory Variability Consideration
Because aPTT reagents vary between laboratories, each facility should calibrate their aPTT range to correspond to anti-Xa activity of 0.3-0.6 IU/mL 1. In cases of heparin resistance (aPTT not responding to appropriate doses), consider measuring anti-Xa levels directly 1.