What is the recommended protocol for transitioning a patient from subcutaneous (subcutaneous) heparin to warfarin (warfarin), considering factors such as international normalized ratio (INR) monitoring and potential bleeding risks?

Transition from Subcutaneous Heparin to Warfarin

Start warfarin at 5 mg daily (or 2.5 mg in elderly/high-risk patients) on the same day as subcutaneous heparin, continue both agents for a minimum of 5 days AND until INR ≥2.0 for at least 24 hours, then discontinue heparin. 1, 2, 3

Initiation Protocol

Starting Warfarin

• Begin warfarin at 5 mg orally once daily while continuing subcutaneous heparin 1, 2, 3
• Use 2.5 mg initial dose in elderly patients, those with poor nutritional status, concurrent medications affecting warfarin metabolism, or underlying liver disease 1, 2
• Avoid loading doses that can raise INR excessively 4

Subcutaneous Heparin Dosing During Overlap

• Continue unfractionated heparin at 250 U/kg subcutaneously twice daily (following initial dose of 333 U/kg) 1
• This weight-based subcutaneous regimen has been shown to be as safe and effective as LMWH for VTE treatment 1

Overlap Duration Requirements

The overlap period is critical and must meet TWO criteria:

• Minimum 5 days of concurrent therapy 1, 2, 3
• INR ≥2.0 for at least 24 hours before discontinuing heparin 1, 2, 3

This dual requirement ensures adequate warfarin effect, as warfarin's anticoagulant effect is delayed despite early INR elevation 3

INR Monitoring Schedule

During Transition

• Check INR 4-6 hours after initial heparin bolus (if using IV heparin concurrently) 1
• Monitor INR every 1-2 days initially during the overlap period 1, 4
• For subcutaneous heparin, draw blood for INR 24 hours after the last subcutaneous injection to avoid heparin interference 3

After Heparin Discontinuation

• Continue frequent INR monitoring (2-4 times per week) immediately after stopping heparin 4
• Gradually lengthen intervals up to maximum 4-6 weeks once stable 4

Target INR and Dose Adjustments

• Target INR is 2.0-3.0 for most indications 1, 2
• Adjust warfarin dose by 5-20% of total weekly dose based on INR values 4
• Do not adjust for a single slightly out-of-range INR 4

Special Populations and Precautions

Renal Impairment

• Exercise caution with subcutaneous heparin in severe renal disease, though specific dosing adjustments are less critical than with LMWH 1
• Warfarin dosing may need adjustment but is not contraindicated in renal disease 2

Hepatic Impairment

• Avoid warfarin in moderate-to-severe liver disease or hepatic coagulopathy 1, 2
• Use lower initial doses with any degree of liver dysfunction 2

Pregnancy

• Avoid warfarin entirely in pregnant or nursing patients due to teratogenicity 1, 2
• Continue heparin throughout pregnancy if anticoagulation needed 2

Critical Pitfalls to Avoid

Premature Heparin Discontinuation

• Never stop heparin before meeting BOTH the 5-day minimum AND INR ≥2.0 for 24 hours criteria 1, 2, 3
• Early INR elevation reflects depletion of factor VII (short half-life) but does not indicate adequate anticoagulation, as factors II and X (longer half-lives) remain elevated 3

Heparin-Induced Thrombocytopenia (HIT)

• Monitor platelet counts every 2-3 days from day 4 to day 14 during heparin therapy 1
• Risk of HIT with unfractionated heparin may be as high as 5%, particularly in post-orthopedic surgery patients 1
• Watch for ≥50% decline in platelet count typically within 5-10 days 1

Timing of INR Measurements

• Avoid drawing INR while heparin effect is present, as heparin can artificially elevate INR 3
• Wait 24 hours after last subcutaneous heparin dose for accurate INR measurement 3

Duration of Anticoagulation

• Continue warfarin for at least 6 months for venous thromboembolism 2
• Specific duration depends on underlying indication and risk factors 2
• For first episode with temporary risk factors, consider discontinuation at 6-12 weeks 1