Therapeutic APTT Range for Pulmonary Embolism on Heparin Drip
For patients with pulmonary embolism on a heparin drip, the therapeutic APTT range should be 1.5-2.5 times the control value, which typically corresponds to 60-85 seconds, depending on the laboratory reagent used. 1
Rationale for APTT Target Range
The therapeutic range of 60-85 seconds corresponds to a plasma heparin level of:
- 0.2 to 0.4 U/mL by protamine titration
- 0.35 to 0.7 U/mL in terms of anti-factor Xa activity 1
This range is critical as studies have demonstrated a significant increase in recurrent venous thromboembolism when APTT values fall below the therapeutic range:
- Patients with DVT and APTT <60 seconds had a 10.7-fold increased risk of recurrent thromboembolism 1
- Subtherapeutic anticoagulation in the first 24-48 hours is associated with treatment failure and increased mortality
Important Laboratory Considerations
- The therapeutic range varies with the responsiveness of the APTT reagent to heparin 1
- Different laboratory instruments may produce significantly different APTT values for the same blood sample
- A study comparing two different laboratory devices found therapeutic ranges of 61-93 seconds and 56-73 seconds respectively 2
- Individual laboratories should establish their own therapeutic ranges based on their specific reagents and instruments
Heparin Dosing Protocol
Initial dosing:
- Bolus: 80 U/kg IV (or 5,000-10,000 IU)
- Initial infusion: 18 U/kg/hour (or approximately 1,300 IU/hour) 1
APTT monitoring schedule:
- First measurement: 6 hours after the initial bolus
- After any dose change: 6-10 hours later
- Once therapeutic: Daily monitoring 1
Dose Adjustment Algorithm
When adjusting heparin based on APTT results:
| APTT Result | Action |
|---|---|
| <35 seconds (<1.2× control) | 80 U/kg bolus, increase infusion by 4 U/kg/hour |
| 35-45 seconds (1.2-1.5× control) | 40 U/kg bolus, increase infusion by 2 U/kg/hour |
| 46-70 seconds (1.5-2.3× control) | No change (therapeutic range) |
| 71-90 seconds (2.3-3× control) | Decrease infusion by 2 U/kg/hour |
| >90 seconds (>3× control) | Stop infusion for 1 hour, then decrease by 3 U/kg/hour |
Clinical Pitfalls and Challenges
Heparin resistance: Some patients require higher doses due to increased heparin binding to plasma proteins or increased clearance 1
Difficulty achieving therapeutic range: Recent research shows that only 26.3% of patients reach therapeutic APTT at 24 hours and 28.4% at 48 hours with standard dosing protocols 3
Laboratory variability: Different reagents and instruments can produce significantly different APTT values, making it essential to use laboratory-specific therapeutic ranges 2
Monitoring challenges: The conventional approach of using a fixed APTT ratio (1.5-2.5× normal) may result in significant underanticoagulation if not calibrated to the specific laboratory system 2
Accelerated clearance: Patients with acute pulmonary embolism may have shortened heparin half-life, requiring more frequent monitoring and dose adjustments 4
For patients who cannot achieve stable therapeutic anticoagulation with unfractionated heparin, consider switching to low molecular weight heparin or fondaparinux, which have more predictable pharmacokinetics and don't require routine monitoring.