When initiating warfarin, should I bridge with heparin or give a loading dose of warfarin?

Warfarin Initiation: Bridge with Heparin, Not Loading Dose

When initiating warfarin therapy, you should always bridge with heparin (or LMWH) and avoid using a loading dose of warfarin alone. The standard approach is to start both agents concurrently on day 1 or 2, continue heparin for at least 5 days, and only discontinue heparin once the INR is ≥2.0 for at least 24 hours on two consecutive measurements 1, 2.

Why Bridging is Mandatory

Warfarin creates a paradoxical prothrombotic state during the first 3-5 days of therapy because it depletes protein C (half-life 6-8 hours) and protein S before adequately reducing clotting factors II, IX, and X (half-lives 24-72 hours) 3. This early depletion of natural anticoagulants can actually increase thrombosis risk, making heparin coverage essential during warfarin initiation 1, 3.

The minimum 5-day overlap requirement exists regardless of when the INR becomes therapeutic, because achieving an INR of 2.0 reflects only the depletion of factor VII (shortest half-life) and does not guarantee adequate reduction of factors II and X 1.

Recommended Bridging Protocol

Heparin Options and Dosing

For most patients, use one of these heparin regimens started concurrently with warfarin:

• Unfractionated heparin (UFH) IV: 80 units/kg bolus, then 18 units/kg/hour infusion, targeting aPTT 1.5-2.5 times control 1
• UFH subcutaneous: 333 units/kg loading dose, then 250 units/kg every 12 hours (unmonitored, fixed-dose) 1, 4
• Enoxaparin: 1 mg/kg subcutaneously every 12 hours 1
• Dalteparin: 200 units/kg subcutaneously daily 1
• Fondaparinux: Weight-based dosing (5 mg if <50 kg; 7.5 mg if 50-100 kg; 10 mg if >100 kg) subcutaneously daily 1

Warfarin Dosing During Bridging

Start warfarin at 2.5-5 mg daily, NOT 10 mg, for most patients 1, 3. The American College of Chest Physicians suggests 10 mg daily for only the first 2 days in healthy outpatients, but this recommendation carries significant caveats 1.

Use reduced initial warfarin doses (2-5 mg daily) for patients who are:

• ≥70 years old 3
• Weight <70 kg 3
• Have chronic liver disease 3
• Taking interacting medications (amiodarone, azole antifungals, macrolides) 3

For elderly patients ≥70 years with weight <70 kg, start with 2-3 mg daily 3. With amiodarone co-administration, reduce warfarin dose by 30-50% 3. With azole antifungals or macrolides, anticipate a 25-40% dose reduction 3.

Discontinuation Criteria

Stop heparin only when ALL of the following are met:

1. At least 5 days of overlap therapy have been completed 1, 2
2. INR ≥2.0 on two consecutive measurements 1, 3, 2
3. The two INR measurements are taken >24 hours apart 3, 2

The FDA label explicitly states: "it is advisable to continue full dose heparin therapy and that warfarin sodium tablets therapy be overlapped with heparin for 4 to 5 days, until warfarin sodium tablets have produced the desired therapeutic response" 2.

Special Populations

Renal Insufficiency (CrCl <30 mL/min)

Use UFH instead of LMWH because UFH is metabolized by the liver, not the kidneys 1, 3, 4. Fixed-dose subcutaneous UFH (250 units/kg every 12 hours) is safe and effective in end-stage renal disease without requiring anti-Xa monitoring 4.

Cancer Patients

The NCCN guidelines recommend the same bridging approach: initiate warfarin concurrently with parenteral anticoagulation and continue both for at least 5 days until INR ≥2 for 24 hours 1. However, direct oral anticoagulants or extended LMWH monotherapy are now preferred over warfarin for cancer-associated VTE 1.

INR Monitoring Schedule

During bridging and initial warfarin therapy:

• Check INR daily until stable in therapeutic range (2.0-3.0) 3, 2
• Once stable, check 2-3 times per week for 1-2 weeks 3
• Then weekly for 1 month 3
• Then monthly thereafter 3

Patients ≥70 years require more frequent monitoring due to greater INR variability 3. During antibiotic therapy, check INR every 1-2 days 3.

Common Pitfalls to Avoid

Do NOT:

• Use 10 mg warfarin loading doses in elderly, low-weight, or liver-diseased patients—this frequently causes supratherapeutic INR and bleeding 3
• Discontinue heparin when INR first reaches 2.0—wait for two consecutive therapeutic INRs >24 hours apart 3, 2
• Use LMWH when creatinine clearance <30 mL/min—use UFH to prevent drug accumulation 3, 4
• Stop heparin before completing the minimum 5-day overlap, even if INR is therapeutic 1, 2

High vs. Low Thrombotic Risk

For high thrombotic risk patients (recent VTE, mechanical mitral valve, atrial fibrillation with prior stroke): maintain aggressive heparin dosing with target aPTT 1.5-2.5 times control throughout bridging and consider extending overlap beyond 5 days if INR remains subtherapeutic 3.

For low thrombotic risk patients (VTE >3 months ago, atrial fibrillation without prior stroke): the standard 5-day overlap is sufficient 3.

The evidence consistently demonstrates that early initiation of warfarin on day 1-2 of heparin therapy reduces hospital length of stay by approximately 4 days without increasing mortality, recurrent thromboembolism, or major bleeding 1.