Flat Rate Heparin Infusion Protocol
The standard protocol for unfractionated heparin (UFH) infusion is a weight-based regimen of 80 U/kg as an initial bolus followed by 18 U/kg/hour infusion, with subsequent dose adjustments based on activated partial thromboplastin time (aPTT) monitoring. 1
Initial Dosing
Standard Weight-Based Protocol
- Initial bolus: 80 U/kg IV (maximum 4000 U)
- Initial infusion: 18 U/kg/hour (maximum 1000 U/hour)
- Target aPTT: 1.5-2.5 times control value (approximately 45-75 seconds)
Alternative Dosing for Specific Conditions
For patients receiving fibrin-specific thrombolytics (alteplase, reteplase, tenecteplase):
- Bolus: 60 U/kg (maximum 4000 U)
- Infusion: 12 U/kg/hour (maximum 1000 U/hour) 1
For patients without thrombolytics:
- Bolus: 60-70 U/kg
- Infusion: 12-15 U/kg/hour 1
Monitoring and Dose Adjustment
aPTT Monitoring Schedule
- First aPTT: 4-6 hours after initiating infusion
- Check aPTT every 6 hours until two consecutive therapeutic values
- Then reduce to daily monitoring 2
- Recheck if clinical status changes (bleeding, recurrent symptoms, hemodynamic instability)
Dose Adjustment Nomogram
| aPTT (seconds) | Action Required |
|---|---|
| <35 (<1.2× control) | 80 U/kg bolus; increase infusion by 4 U/kg/hour |
| 35-45 (1.2-1.5× control) | 40 U/kg bolus; increase infusion by 2 U/kg/hour |
| 46-70 (1.5-2.3× control) | No change |
| 71-90 (2.3-3.0× control) | Decrease infusion by 2 U/kg/hour |
| >90 (>3.0× control) | Stop infusion for 1 hour, then decrease by 3 U/kg/hour |
| [1,2] |
Special Populations
Elderly Patients
- Consider starting with a lower infusion rate (15 U/kg/hour) to avoid supratherapeutic aPTT response 3
- Age ≥67 years is a risk factor for supratherapeutic response
Morbidly Obese Patients
- Standard weight-based protocols with maximum doses may result in delayed therapeutic anticoagulation
- Consider using adjusted body weight for dosing:
- Dosing weight = IBW + 0.3(ABW - IBW) or
- Dosing weight = IBW + 0.4(ABW - IBW) 4
Renal Failure
- UFH is preferred over LMWH in patients with significant renal dysfunction
- Use standard weight-based dosing with careful monitoring 2
Pediatric Patients
- Loading dose: 75-100 U/kg IV bolus over 10 minutes
- Maintenance dose:
- Infants <2 months: 28 U/kg/hour
- Children >1 year: 18-20 U/kg/hour
- Target aPTT: 60-85 seconds 2, 5
Transitioning to Oral Anticoagulants
Transitioning to Warfarin
- Start warfarin simultaneously with heparin
- Continue heparin until INR reaches therapeutic range (2.0-3.0) for at least 2 consecutive days
- Minimum 5-7 days of therapeutic anticoagulation with heparin 2
Transitioning to Direct Oral Anticoagulants
- Stop heparin infusion immediately before administering first dose of oral anticoagulant
- No overlap period required 2
Common Pitfalls and Considerations
Heparin Resistance
- Defined as requiring ≥35,000 units/day without achieving therapeutic aPTT
- Consider monitoring with anti-Xa levels (target 0.35-0.7 units/mL) instead of aPTT
- Common causes: antithrombin deficiency, elevated factor VIII or fibrinogen levels 2
Laboratory Variability
- aPTT results can vary significantly between laboratories due to reagent differences
- Each institution should calibrate their therapeutic range based on specific reagents and equipment 2
Bleeding Risk
- Monitor platelet count daily to detect heparin-induced thrombocytopenia (HIT)
- HIT typically occurs between 5-15 days of treatment
- If major bleeding occurs, immediately terminate heparin infusion
- Consider reversal with protamine sulfate in severe cases 2
Inadequate Anticoagulation
- Failure to achieve therapeutic aPTT within 24 hours is associated with higher risk of recurrent thromboembolism
- Smoking is a risk factor for subtherapeutic response 3
By following this protocol for flat rate heparin infusion, clinicians can effectively manage anticoagulation while minimizing the risk of complications.