What is the recommended protocol for transitioning a patient from Eliquis (apixaban) to Coumadin (warfarin)?

Transitioning from Eliquis (Apixaban) to Coumadin (Warfarin)

Start warfarin at the usual initial dose (typically 5 mg daily) while simultaneously beginning a parenteral anticoagulant (LMWH or UFH) at the exact time of the next scheduled apixaban dose, continuing both agents for at least 5 days until INR ≥2.0 for at least 24 hours. 1, 2, 3

Transition Protocol

Step 1: Initiate Warfarin and Bridging Anticoagulation

• Discontinue apixaban and immediately start warfarin at 5 mg daily (or 2.5 mg if liver disease or interacting medications are present) 1, 2
• Do not use a loading dose of warfarin, as the expected maintenance dose is safer 1
• Begin parenteral anticoagulation at the exact time the next apixaban dose would have been due to ensure no gap in anticoagulation coverage 1, 2, 3

Step 2: Parenteral Anticoagulant Options

Low Molecular Weight Heparin (LMWH):

• Dalteparin 200 units/kg subcutaneously once daily, OR 1, 2
• Enoxaparin 1 mg/kg subcutaneously every 12 hours 1, 2

Unfractionated Heparin (UFH):

• IV: 80 units/kg bolus, then 18 units/kg/hour infusion (targeting aPTT 2-2.5× control), OR 1, 2
• SC: 333 units/kg loading dose, then 250 units/kg every 12 hours 1, 2

Step 3: Monitoring During Transition

• Check INR daily during the transition period 1, 2
• Obtain baseline labs before transition: CBC, PT, aPTT, and renal/hepatic function 1, 2
• Monitor renal function during transition, as changes in kidney function affect both apixaban clearance and warfarin dosing requirements 2

Step 4: Discontinue Parenteral Anticoagulation

Stop the parenteral anticoagulant only when BOTH criteria are met: 1, 2

• At least 5 days of overlap therapy completed, AND
• INR ≥2.0 for at least 24 hours (target INR 2.0-3.0)

Step 5: Ongoing Warfarin Management

• Target INR range: 2.0-3.0 for most indications (atrial fibrillation, VTE) 4, 1, 2
• INR monitoring frequency: 1
  • Twice or three times weekly during the first 2 weeks
  • Once weekly thereafter
  • Every 4 weeks once stable
• Duration of therapy: 1, 2
  • Minimum 3 months for VTE
  • Indefinite for atrial fibrillation or recurrent VTE

Special Considerations for High-Risk Patients

Patients at Very High Thrombotic Risk

For patients with recent VTE, mechanical heart valve, or severe hypercoagulable state: 1, 2

• Ensure absolutely no gap in anticoagulation coverage
• Start the parenteral agent at the exact time the next apixaban dose would have been due
• Consider more frequent INR monitoring

Patients with Renal Dysfunction

• Assess renal function before and during transition 2
• Apixaban has 27% renal clearance, so patients with severe renal dysfunction may have prolonged apixaban effects 5
• For patients with CrCl <25 mL/min, warfarin is preferred over apixaban per guidelines 4

Patients with Mechanical Heart Valves

• Warfarin is mandatory for mechanical heart valves 4
• Apixaban is contraindicated and has been shown to be less effective than warfarin for preventing valve thrombosis 6
• Target INR 2.0-3.0 or 2.5-3.5 depending on valve type and location 4

Common Pitfalls and How to Avoid Them

Pitfall 1: Starting Warfarin Without Bridging

• Avoid: Starting warfarin alone without parenteral anticoagulation 3
• Why: Apixaban affects INR measurements, making initial INR values unreliable for determining adequate anticoagulation 3
• Solution: Always use parenteral bridging until therapeutic INR is achieved 1, 2

Pitfall 2: Stopping Parenteral Anticoagulation Too Early

• Avoid: Discontinuing LMWH/UFH before meeting both criteria (≥5 days overlap AND INR ≥2.0 for ≥24 hours) 1, 2
• Why: Risk of thromboembolism during subtherapeutic anticoagulation
• Solution: Strictly adhere to the dual criteria before stopping bridging therapy 1, 2

Pitfall 3: Inadequate Monitoring of Concomitant Medications

• Assess for: Antiplatelet agents (aspirin, clopidogrel) or NSAIDs that increase bleeding risk 2
• Action: Consider discontinuing or adjusting doses of these medications during transition 2

Pitfall 4: Using Loading Doses of Warfarin

• Avoid: Loading doses of warfarin (e.g., 10 mg) 1
• Why: Increased risk of supratherapeutic INR and bleeding without faster achievement of therapeutic anticoagulation
• Solution: Use standard 5 mg daily dosing (or 2.5 mg in high-risk patients) 1, 2