Therapeutic Dosing of Unfractionated Heparin for Anticoagulation
The therapeutic dose of unfractionated heparin (UFH) for anticoagulation is an initial intravenous bolus of 80 units/kg followed by an initial infusion of 18 units/kg/hour, with subsequent dose adjustments to maintain an activated partial thromboplastin time (aPTT) of 1.5 to 2.5 times control (approximately 50-70 seconds). 1, 2, 3
Intravenous UFH Dosing Protocol
Initial Dosing
- Bolus: 80 units/kg (maximum 4000 units in some protocols)
- Initial infusion: 18 units/kg/hour (maximum 1000 units/hour in some protocols) 1
Monitoring and Dose Adjustment
- Target aPTT: 1.5-2.5 times control (approximately 50-70 seconds) 1, 2
- First aPTT check: 4-6 hours after initiation
- Subsequent monitoring: Every 4-6 hours until stable, then daily 2
Dose Adjustment Protocol
Based on aPTT results, adjust the infusion according to this nomogram 2:
| aPTT (seconds) | Bolus (U/kg) | Hold (min) | Rate Change | Repeat aPTT |
|---|---|---|---|---|
| < 35 | 80 | 0 | Increase by 4 U/kg/h | 4 hours |
| 35-45 | 40 | 0 | Increase by 2 U/kg/h | 4 hours |
| 46-70 (target) | 0 | 0 | No change | Next day |
| 71-90 | 0 | 0 | Decrease by 2 U/kg/h | 4 hours |
| > 90 | 0 | 60 | Decrease by 3 U/kg/h | 4 hours |
Alternative Subcutaneous UFH Dosing
For situations where intravenous administration is not feasible:
- Initial dose: 333 units/kg subcutaneously
- Maintenance: 250 units/kg subcutaneously every 12 hours 1, 4
- This fixed-dose, unmonitored approach has been shown to be comparable to LMWH in effectiveness and safety 4
Special Considerations
Obesity
- Standard weight-based protocols with maximum dose caps can result in significant delays in achieving therapeutic anticoagulation in obese patients 5, 6
- For morbidly obese patients, consider using a modified dosing weight:
Renal Dysfunction
- UFH is the preferred agent for patients with CrCl <30 mL/min as it is primarily metabolized by the liver 1
- More careful monitoring may be required in patients with severe renal dysfunction 2
Heparin Resistance
- Defined as requiring unusually high doses of heparin to achieve therapeutic aPTT 1
- Causes include antithrombin deficiency, increased heparin clearance, elevated levels of heparin-binding proteins, or high levels of factor VIII and/or fibrinogen 1
- In patients requiring ≥35,000 units/day, consider adjusting doses based on anti-Xa levels (target range 0.3-0.7 units/mL) rather than aPTT 1
Monitoring Considerations
- The therapeutic range of aPTT (1.5-2.5 times control) was established based on retrospective studies from the 1970s 1
- aPTT response varies significantly between reagents and instruments, with aPTT results ranging from 48 to 108 seconds for the same heparin concentration 1
- Institutions should adapt their therapeutic aPTT range based on the responsiveness of their specific reagent and coagulometer 1
- Monitor platelet counts daily to detect heparin-induced thrombocytopenia 1, 2
Duration of Therapy
For venous thromboembolism:
- Minimum 5-7 days of therapeutic anticoagulation 2
- When transitioning to warfarin, continue UFH until INR is therapeutic (2.0-3.0) for 2 consecutive days 2
The higher-dose regimen (80 units/kg bolus followed by 18 units/kg/hour) has been shown to achieve therapeutic anticoagulation more rapidly than lower-dose regimens, which is critical for reducing morbidity and mortality in patients with thrombotic conditions 8.