For a patient with Factor V Leiden on warfarin, should I use low or high intensity unfractionated heparin infusion?

Heparin Intensity for Factor V Leiden Patients on Warfarin

Use high-intensity (therapeutic dose) unfractionated heparin with weight-based dosing: 80 units/kg IV bolus followed by 18 units/kg/hour continuous infusion, targeting an aPTT of 1.5-2.5 times control. 1

Rationale for High-Intensity Dosing

Factor V Leiden does not change the fundamental approach to acute VTE treatment—these patients require full therapeutic anticoagulation just like any other VTE patient. 1 The presence of Factor V Leiden actually represents a hypercoagulable state that increases thrombotic risk, making adequate anticoagulation even more critical. 2

Key evidence supporting high-intensity dosing:

• Randomized trials demonstrate that lower heparin doses result in significantly higher VTE recurrence rates. In the landmark study by Hull et al., patients receiving lower doses (15,000 units/day subcutaneously) had higher recurrence rates than those receiving 30,000 units/day by continuous IV infusion. 1

• Weight-based dosing (80 units/kg bolus, 18 units/kg/hour infusion) significantly reduces recurrent thromboembolism compared to fixed lower doses. Raschke et al. demonstrated that patients on weight-adjusted regimens received higher doses within 24 hours and had significantly lower recurrence rates. 1

• Failure to achieve therapeutic aPTT within 24 hours is associated with a 25% risk of recurrent VTE. Patients who achieved therapeutic aPTT in <24 hours also had lower in-hospital and 30-day mortality rates. 1

Specific Dosing Protocol

Initial dosing: 1, 3

• IV bolus: 80 units/kg (maximum 5,000 units for some indications, but VTE treatment typically uses full weight-based dosing)
• Continuous infusion: 18 units/kg/hour
• Target aPTT: 1.5-2.5 times control (approximately 50-70 seconds), corresponding to anti-Factor Xa levels of 0.3-0.7 IU/mL 1

Dose adjustments using aPTT-based nomogram: 1

• aPTT <35 seconds (<1.2× control): 80 U/kg bolus; increase infusion by 4 U/kg/h
• aPTT 35-45 seconds (1.2-1.5× control): 40 U/kg bolus; increase infusion by 2 U/kg/h
• aPTT 46-70 seconds (1.5-2.3× control): No change
• aPTT 71-90 seconds (2.3-3.0× control): Reduce infusion by 2 U/kg/h
• aPTT >90 seconds (>3.0× control): Stop infusion for 1 hour, then reduce by 3 U/kg/h

Critical Pitfalls to Avoid

Do not use "low-dose" or prophylactic heparin regimens for active VTE. 1 Low-dose heparin (5,000 units subcutaneously every 8-12 hours) is only appropriate for VTE prophylaxis, not treatment. 3 Your patient with Factor V Leiden who is already on warfarin likely has a history of VTE or is being bridged for a procedure—either scenario requires therapeutic dosing.

Do not assume Factor V Leiden heterozygotes need less anticoagulation. 2 While heterozygotes have lower baseline risk than homozygotes, once VTE occurs, they require full therapeutic anticoagulation. A case report documented recurrent bilateral PE in a Factor V Leiden heterozygote despite initial heparin therapy, emphasizing the need for aggressive anticoagulation. 2

Monitor aPTT every 6 hours initially until therapeutic range is stable, then daily. 1 Inadequate monitoring leads to subtherapeutic anticoagulation and increased recurrence risk.

Special Considerations for Warfarin Bridge

If you're bridging this patient for a procedure or managing warfarin interruption:

• Continue full-dose heparin until INR is therapeutic (2.0-3.0) for at least 24 hours. 3, 4 Overlap heparin and warfarin for 4-5 days minimum. 5, 4

• For high-risk patients requiring warfarin interruption >1 week, therapeutic-dose heparin bridging is appropriate. 1 Factor V Leiden with prior VTE qualifies as high-risk.

Why Not Low-Intensity?

Low-intensity heparin regimens (such as those used for acute coronary syndromes: 60-70 units/kg bolus, 12-15 units/kg/hour infusion) are designed for different pathophysiology and carry unacceptably high VTE recurrence rates. 1, 6 The doses recommended for acute coronary syndromes are explicitly lower than those used for VTE treatment. 1

The evidence is unequivocal: therapeutic-intensity, weight-based heparin dosing reduces VTE recurrence and mortality compared to lower-intensity regimens. 1, 5