What to do if a patient develops a Deep Vein Thrombosis (DVT) while on Eliquis (apixaban)?

Management of Breakthrough DVT on Apixaban

If a patient develops DVT while on therapeutic apixaban, immediately investigate for medication non-adherence, drug interactions, and underlying conditions (particularly cancer and antiphospholipid syndrome), then switch to low molecular weight heparin (LMWH) as the preferred alternative anticoagulant. 1

Initial Assessment

When a patient experiences breakthrough DVT on apixaban, the first critical step is confirming this is a true treatment failure rather than a compliance or dosing issue:

• Verify medication adherence - Confirm the patient has been taking apixaban as prescribed without missed doses 1
• Confirm appropriate dosing - Ensure the patient is receiving the correct therapeutic dose (10 mg twice daily for 7 days, then 5 mg twice daily for DVT treatment, or 2.5 mg twice daily if on extended prophylaxis) 2
• Assess for drug interactions - Check for P-glycoprotein inhibitors or CYP3A4 inhibitors that may alter apixaban levels, and conversely, strong inducers that may reduce efficacy 1
• Evaluate renal function - Calculate creatinine clearance using Cockcroft-Gault formula, as impaired renal function affects apixaban dosing requirements 1

Identify Underlying Causes

Several conditions predispose to anticoagulant failure and must be actively sought:

• Active malignancy - Cancer is a major risk factor for recurrent VTE despite anticoagulation and requires specific management 1
• Antiphospholipid syndrome - This condition has reduced efficacy with DOACs; patients with confirmed antiphospholipid syndrome should receive vitamin K antagonist (VKA) therapy with target INR 2.5 instead 1
• Heparin-induced thrombocytopenia (HIT) - If the patient recently received heparin products before apixaban, consider HIT as a cause of recurrent thrombosis 1

Recommended Anticoagulant Switch

The American Society of Hematology guidelines provide a conditional recommendation favoring LMWH over continuing or switching to another DOAC for breakthrough VTE, though this is based on very low certainty evidence. 1

Preferred approach:

• Switch to LMWH at therapeutic dosing (e.g., enoxaparin 1 mg/kg subcutaneously twice daily or 1.5 mg/kg once daily) 1
• LMWH is particularly preferred if:
  • Active cancer is present 1
  • Antiphospholipid syndrome is confirmed or suspected 1
  • The patient requires more predictable anticoagulation with monitoring capability 1

Alternative considerations:

• VKA therapy (warfarin with target INR 2.0-3.0) may be considered, particularly in antiphospholipid syndrome where it is specifically recommended over DOACs 1
• Initiate VKA with overlapping parenteral anticoagulation until INR is ≥2.0 for at least 24 hours 1

Special Population Management

Cancer-Associated Thrombosis

If breakthrough DVT occurs in a cancer patient on apixaban:

• Switch to LMWH monotherapy for at least 3-6 months or as long as cancer or chemotherapy is ongoing 1
• LMWH regimens include dalteparin 200 IU/kg once daily (maximum 18,000 IU) or equivalent 1
• Extended anticoagulation with no scheduled stop date is recommended for active cancer 1

Antiphospholipid Syndrome

• Transition to adjusted-dose VKA (target INR 2.5) with overlapping parenteral anticoagulation 1
• DOACs including apixaban have reduced efficacy in this population 1

Duration of Anticoagulation After Breakthrough Event

• Minimum 3 months of therapeutic anticoagulation is required for any acute VTE 1
• Extended-phase anticoagulation (indefinite duration) should be strongly considered for breakthrough thrombosis, as this represents either unprovoked VTE or VTE with persistent risk factors 1
• Periodic reassessment of bleeding risk versus thrombotic benefit is essential for patients on extended anticoagulation 1

Common Pitfalls to Avoid

• Do not simply increase apixaban dose - There is no evidence supporting dose escalation of apixaban for breakthrough thrombosis 2
• Do not switch to another DOAC without investigation - Switching from one DOAC to another without identifying the underlying cause may result in continued treatment failure 1
• Do not overlook medication interactions - P-glycoprotein and CYP3A4 interactions can significantly reduce apixaban efficacy 1
• Do not delay switching anticoagulants - Once breakthrough thrombosis is confirmed and compliance/dosing verified, prompt transition to alternative anticoagulation is warranted 1

Monitoring After Switch

• If switched to LMWH: Anti-Xa monitoring is generally not required for standard dosing, but may be considered in renal impairment, extremes of body weight, or pregnancy 1
• If switched to VKA: Target INR 2.0-3.0 with monitoring per standard protocols 1
• Reassess for recurrent VTE and bleeding complications regularly 1