A patient on apixaban (Eliquis) 5 mg twice daily has a newly diagnosed deep‑vein thrombosis of the left lower extremity; how should the anticoagulation regimen be adjusted?

Management of Breakthrough DVT on Therapeutic Apixaban

Increase apixaban to 10 mg twice daily for 7 days, then continue 5 mg twice daily for at least 3 months, treating this as a new acute DVT event. 1, 2

Immediate Clinical Assessment

Before adjusting therapy, perform the following evaluation:

• Calculate creatinine clearance using the Cockcroft-Gault equation to ensure the patient can safely metabolize apixaban (avoid if CrCl <15 mL/min). 3
• Obtain a complete blood count to establish baseline hemoglobin for future bleeding surveillance. 3
• Measure liver function tests (ALT, AST, bilirubin) to exclude hepatic impairment that would contraindicate continued apixaban use. 3
• Review all concomitant medications for strong dual P-glycoprotein and CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin) or inducers (rifampin, carbamazepine, phenytoin) that alter apixaban levels. 3, 4

Investigation of Breakthrough Thrombosis

• Verify therapeutic adherence by directly questioning the patient about missed doses, as non-compliance is the most common cause of breakthrough VTE on DOACs. 2
• Assess for underlying malignancy if not previously diagnosed, as cancer-associated thrombosis may require switching to low-molecular-weight heparin rather than dose escalation. 5, 1
• Screen for antiphospholipid syndrome with lupus anticoagulant, anticardiolipin antibodies, and anti-β2-glycoprotein I antibodies, as this condition mandates switching from apixaban to LMWH or warfarin. 1
• Consider drug-drug interactions that may have reduced apixaban bioavailability, particularly recent initiation of CYP3A4/P-gp inducers. 3

Dosing Algorithm for Acute DVT Treatment

The FDA-approved regimen for acute DVT treatment is distinct from atrial fibrillation dosing:

• Days 1–7: Apixaban 10 mg orally twice daily (loading phase to rapidly achieve therapeutic anticoagulation). 1, 2
• Day 8 onward: Apixaban 5 mg orally twice daily for a minimum of 3 months. 1, 2

Critical caveat: Do NOT apply atrial fibrillation dose-reduction criteria (age ≥80 years, weight ≤60 kg, serum creatinine ≥1.5 mg/dL) to VTE treatment—the full 10 mg/5 mg regimen is mandatory regardless of these factors. 3, 4

Why Not Switch to Another Anticoagulant?

• The American Society of Hematology recommends LMWH over DOACs for breakthrough VTE during therapeutic vitamin K antagonist (warfarin) therapy 5, but this guideline does not address breakthrough events on DOACs specifically.
• Apixaban has only 27% renal excretion compared to rivaroxaban (66%) or dabigatran (80%), making it less susceptible to pharmacokinetic variability in patients with fluctuating renal function. 3
• Switching to LMWH should be reserved for patients with confirmed antiphospholipid syndrome, active malignancy requiring cancer-directed therapy, or documented non-adherence where injectable therapy ensures compliance. 5, 1

Duration of Extended Therapy

After completing the initial 3-month treatment course:

• For unprovoked DVT or persistent risk factors: Continue anticoagulation indefinitely with either apixaban 5 mg twice daily (full dose) or 2.5 mg twice daily (reduced secondary prevention dose) after at least 6 months of treatment. 5, 3, 2
• The American Society of Hematology gives a conditional recommendation that either standard or reduced-dose apixaban may be used for extended therapy, though studies were not powered to directly compare the two strategies. 5
• For provoked DVT with resolved risk factors: Discontinue anticoagulation after 3 months. 1

Common Pitfalls to Avoid

• Do not continue the patient's current 5 mg twice-daily dose without the 7-day loading phase at 10 mg twice daily—this subtherapeutic approach fails to address acute thrombus burden. 1, 4
• Do not use the 2.5 mg twice-daily dose during acute treatment; this dose is reserved exclusively for post-surgical prophylaxis or extended secondary prevention after completing initial therapy. 4, 2
• Do not employ parenteral bridging with LMWH or unfractionated heparin when transitioning to the higher apixaban dose, as the 10 mg twice-daily regimen provides immediate therapeutic anticoagulation. 3
• Do not assume the breakthrough event represents apixaban failure without first excluding non-adherence, drug interactions, and underlying prothrombotic conditions. 5

Monitoring and Follow-Up

• Reassess renal function at 1 month and then at least annually, as changes in creatinine clearance may affect drug clearance. 3
• Perform repeat compression ultrasound at 1 week to document thrombus stability or progression. 5
• Calculate HAS-BLED score to quantify bleeding risk (score ≥3 indicates high risk requiring closer surveillance), though this does not contraindicate anticoagulation. 3