How should I transition a patient from apixaban (Eliquis) to warfarin using enoxaparin (low‑molecular‑weight heparin) as a bridge?

Transitioning from Apixaban to Warfarin with Enoxaparin Bridge

When transitioning from apixaban (Eliquis) to warfarin, discontinue apixaban and immediately start both therapeutic-dose enoxaparin (1 mg/kg subcutaneously every 12 hours or 1.5 mg/kg once daily) and warfarin (5 mg daily for most patients, 10 mg for young healthy outpatients) at the time the next apixaban dose would have been due, continuing both medications overlapped for at least 5 days until INR reaches 2.0-3.0 on two consecutive measurements, then discontinue enoxaparin. 1, 2, 3

Detailed Transition Protocol

Step 1: Discontinue Apixaban and Initiate Bridge Therapy

• Stop apixaban at its regularly scheduled time (do not give the next dose). 1
• Start enoxaparin immediately at therapeutic dosing at the exact time the next apixaban dose would have been scheduled:
  • 1 mg/kg subcutaneously every 12 hours, OR
  • 1.5 mg/kg subcutaneously once daily 2, 3
• Start warfarin concurrently with enoxaparin:
  • 5 mg daily for elderly patients (≥60 years), hospitalized patients, or those with poor nutritional status
  • 10 mg daily for young (<60 years), healthy outpatients 2, 3

Step 2: Overlap Period (Critical Phase)

• Continue both enoxaparin and warfarin together for a minimum of 5 days. 3, 2
• Monitor INR daily starting on day 3 of warfarin therapy. 3
• Do not discontinue enoxaparin until BOTH conditions are met:
  • At least 5 days of overlap therapy completed, AND
  • INR is therapeutic (2.0-3.0) on two consecutive measurements 3, 2

The typical duration of this overlap is 8-10 days in clinical practice, significantly longer than the minimum 5 days due to real-world INR monitoring schedules. 4

Step 3: Discontinue Enoxaparin

• Stop enoxaparin only when the INR has been therapeutic (2.0-3.0) for two consecutive measurements taken at least 24 hours apart AND at least 5 days of overlap have been completed. 3, 2
• Continue warfarin indefinitely with target INR of 2.5 ± 0.5 (range 2.0-3.0) for most indications. 3

Special Population Considerations

Renal Impairment

• Prefer unfractionated heparin over enoxaparin in patients with significant renal dysfunction (CrCl <30 mL/min) due to accumulation risk with LMWH. 2
• If enoxaparin must be used, consider anti-Xa monitoring in severe renal impairment. 2

Cancer Patients

• Consider continuing enoxaparin long-term (at least 6 months) rather than transitioning to warfarin in cancer patients with venous thromboembolism, as LMWH demonstrates superior outcomes in this population. 5, 2
• If transition to warfarin is necessary despite cancer diagnosis, follow the standard bridging protocol above. 5

High Thrombotic Risk Patients

• Do not reduce enoxaparin dosing during the bridge period, even if minor bleeding occurs—maintain full therapeutic doses throughout. 2
• Ensure no gaps in anticoagulation coverage, as apixaban's anticoagulant effect dissipates within 12-24 hours of the last dose. 1

Monitoring Requirements

INR Monitoring Schedule

• Begin INR testing on day 3 of warfarin therapy. 3
• Check INR daily until therapeutic and stable. 3
• Obtain two consecutive therapeutic INRs (24 hours apart minimum) before discontinuing enoxaparin. 3, 2

Anti-Xa Monitoring (Usually Not Required)

• Routine anti-Xa monitoring is not necessary for most patients receiving standard enoxaparin dosing. 2
• Consider anti-Xa monitoring in specific situations:
  • Extreme body weight (<50 kg or >150 kg)
  • Pregnancy
  • Recurrent thrombosis despite treatment
  • Renal insufficiency (CrCl 30-50 mL/min) 2
• Therapeutic anti-Xa range for enoxaparin: 0.3-0.7 IU/mL (measured 4 hours post-dose for twice-daily dosing). 2

Critical Pitfalls to Avoid

Do Not Skip the Bridge

Never transition directly from apixaban to warfarin without enoxaparin bridging. Unlike the reverse transition (warfarin to apixaban, which requires no bridge), this direction requires full anticoagulation coverage because warfarin takes 5-7 days to achieve therapeutic effect while apixaban's effect wanes within 12-24 hours, creating a dangerous gap in anticoagulation. 1, 3

Do Not Confuse Dosing Regimens

Do not use prophylactic enoxaparin doses (40 mg daily) for bridging therapy. Therapeutic bridging requires 1 mg/kg every 12 hours or 1.5 mg/kg once daily—prophylactic dosing provides inadequate anticoagulation and increases thrombotic risk. 2

Do Not Stop Enoxaparin Prematurely

Do not discontinue enoxaparin based on a single therapeutic INR. Warfarin's effect on INR initially reflects depletion of factor VII (short half-life) before adequate reduction of factors II and X (longer half-lives), meaning early INR elevation may not represent full anticoagulation. Require both 5 days minimum overlap AND two consecutive therapeutic INRs. 3

Do Not Reduce Enoxaparin for Minor Bleeding

Do not empirically reduce enoxaparin dosing for minor bleeding without specialist consultation. Dose reduction creates thrombotic risk; instead, address local bleeding sources and reassess bleeding risk versus thrombotic risk with appropriate consultation. 2

Why This Transition Differs from the Reverse

The apixaban-to-warfarin transition requires bridging while the warfarin-to-apixaban transition does not, because DOACs like apixaban reach therapeutic levels within 3-4 hours, whereas warfarin requires 5-7 days to achieve therapeutic anticoagulation. 6, 1 When stopping apixaban, its anticoagulant effect dissipates rapidly (within 12-24 hours), necessitating immediate enoxaparin coverage to prevent a thrombotic gap during warfarin's onset period. 1, 3