Recommended Heparin Bolus Dose and Continuous Infusion Rate for Anticoagulation Therapy
For therapeutic anticoagulation with unfractionated heparin, the recommended regimen is an initial IV bolus of 80 units/kg followed by a continuous infusion of 18 units/kg/hour, with dose adjustments based on aPTT monitoring to maintain levels at 1.5-2.5 times control value. 1, 2
Initial Dosing Recommendations
Weight-Based Dosing (Preferred Approach)
- Initial bolus: 80 units/kg IV
- Continuous infusion: 18 units/kg/hour
- This weight-based approach has been shown to achieve therapeutic anticoagulation more rapidly and reduce recurrent thromboembolism compared to fixed-dose regimens 1, 2
Fixed-Dose Alternative
- Initial bolus: 5,000 units IV
- Continuous infusion: 32,000-40,000 units/24 hours (approximately 1,330-1,670 units/hour)
- This approach is less preferred as it may lead to delays in achieving therapeutic anticoagulation, particularly in larger patients 1, 3
Indication-Specific Dosing
Venous Thromboembolism (VTE)
Acute Coronary Syndromes
- Unstable angina/NSTEMI:
STEMI with Fibrinolytic Therapy
Monitoring and Dose Adjustment
The goal is to maintain the aPTT at 1.5-2.5 times the control value, which corresponds to a heparin level of 0.2-0.4 U/mL by protamine titration or 0.35-0.7 U/mL by anti-factor Xa activity 1, 2.
Recommended Dose Adjustment Protocol
| aPTT (seconds) | aPTT (× control) | Action |
|---|---|---|
| <35 | <1.2 | 80 units/kg bolus; increase infusion rate by 4 units/kg/hour |
| 35-45 | 1.2-1.5 | 40 units/kg bolus; increase infusion rate by 2 units/kg/hour |
| 46-70 | 1.5-2.3 | No change (therapeutic range) |
| 71-90 | 2.3-3.0 | Reduce infusion rate by 2 units/kg/hour |
| >90 | >3.0 | Stop infusion for 1 hour, then reduce rate by 3 units/kg/hour |
- Check aPTT 6 hours after starting therapy or after any dose change 1, 2
- Once stable, check aPTT daily 2
Special Considerations
Obesity
- Standard weight-based protocols with maximum doses may result in significant delays in achieving therapeutic anticoagulation in obese patients 4
- Consider using actual body weight for initial dosing in obese patients, without arbitrary dose capping 2
Renal Impairment
- Unfractionated heparin is preferred over LMWH in severe renal impairment 2
- No initial dose adjustment is required, but more frequent monitoring may be necessary
Heparin Resistance
- Some patients may require higher doses to achieve therapeutic aPTT
- Consider monitoring with anti-factor Xa levels (target 0.35-0.67 U/mL) rather than continuing to escalate heparin doses in patients requiring >35,000 units/day 5
Safety Considerations
Major bleeding occurs in approximately 1.9% of patients on therapeutic heparin 2
Risk factors for bleeding include:
- High heparin doses
- Concomitant use of fibrinolytic agents or antiplatelet drugs
- Recent surgery or trauma
- Age >60 years
- Renal insufficiency
- Multiple comorbidities 2
Monitor platelet count regularly to detect heparin-induced thrombocytopenia (HIT) 2
Duration of Therapy
- For VTE, continue heparin for at least 5 days and until INR is therapeutic (2.0-3.0) for at least 24 hours when transitioning to warfarin 2
Weight-based heparin dosing is critical for achieving therapeutic anticoagulation quickly and reducing the risk of recurrent thromboembolism. The evidence strongly supports using 80 units/kg as an initial bolus followed by 18 units/kg/hour as a continuous infusion, with dose adjustments based on aPTT monitoring.