Should a patient with a history of pulmonary embolism, recently discharged from the hospital, and experiencing left leg swelling, who has been off Eliquis (apixaban) for a year, resume anticoagulation therapy to prevent another VTE event?

Immediate Resumption of Anticoagulation is Strongly Recommended

You should immediately resume Eliquis (apixaban) and urgently evaluate this patient for a new deep vein thrombosis (DVT), as left leg swelling in a patient with prior unprovoked PE who has been off anticoagulation for a year represents a high-risk scenario for recurrent venous thromboembolism. 1

Urgent Diagnostic Workup Required

• Obtain compression ultrasonography (CUS) of the left leg immediately to confirm or exclude proximal DVT, as this is a Class I recommendation for patients with clinical suspicion of PE or DVT 1
• If CUS shows proximal DVT, this confirms recurrent VTE and mandates immediate anticoagulation 1
• Consider D-dimer testing only if clinical probability is low to intermediate; do not rely on D-dimer if clinical suspicion is high 1

Why Anticoagulation Should Be Resumed

This patient has recurrent unprovoked VTE (at least one previous PE episode), which mandates indefinite anticoagulation. 1 The European Society of Cardiology explicitly states that patients with recurrent VTE not related to a major transient or reversible risk factor must continue oral anticoagulant treatment indefinitely 1

Key Risk Stratification Points:

• The original PE was likely unprovoked (no mention of surgery, trauma, or other transient risk factors), which carries a 4.5% annual recurrence risk after stopping anticoagulation 1
• Being off anticoagulation for one year significantly increases recurrence risk, with rates potentially reaching 10% in the first year after withdrawal 1
• This appears to be a second unprovoked VTE event, which has the strongest indication for indefinite anticoagulation across all guidelines 1

Immediate Treatment Protocol

Acute Phase Management:

• Restart apixaban 10 mg twice daily for 7 days, then 5 mg twice daily as per FDA-approved dosing for acute VTE treatment 2
• This regimen was proven noninferior to enoxaparin/warfarin in the AMPLIFY trial with lower bleeding risk 2, 3
• Do not delay anticoagulation while awaiting imaging if clinical suspicion is high and bleeding risk is acceptable 1

Alternative if Apixaban is Contraindicated:

• If severe renal impairment (CrCl <25 mL/min) or antiphospholipid antibody syndrome is present, use vitamin K antagonist (VKA) with LMWH bridging instead 1
• Check renal function immediately as this affects NOAC dosing and safety 4

Long-Term Management Strategy

After confirming recurrent VTE, this patient requires indefinite anticoagulation with no scheduled stop date. 1

Specific Recommendations:

• Continue apixaban 5 mg twice daily indefinitely after the initial 7-day treatment phase 1, 4
• For extended therapy beyond 6 months, consider reduced-dose apixaban 2.5 mg twice daily, which was superior to placebo in AMPLIFY-EXT with similar bleeding rates 2, 3
• Reassess bleeding risk, drug tolerance, and renal/hepatic function at regular intervals (at least annually) 1, 4

Bleeding Risk Assessment:

The CHEST guidelines stratify bleeding risk as follows 1:

• Low bleeding risk: Recommend extended anticoagulation (Grade 1B) 1
• Moderate bleeding risk: Suggest extended anticoagulation (Grade 2B) 1
• High bleeding risk: Consider 3 months only, but even here extended therapy may be suggested (Grade 2B) 1

High bleeding risk factors include: advanced age, previous bleeding, anemia, active cancer, previous stroke, chronic renal/hepatic disease, concomitant antiplatelet therapy 4

Critical Follow-Up Actions

• Schedule routine re-evaluation at 3-6 months after resuming anticoagulation to assess for chronic complications 1, 4, 5
• Refer to pulmonary hypertension/CTEPH expert center if patient remains symptomatic with mismatched perfusion defects beyond 3 months 1, 4, 5
• Implement integrated care model to ensure optimal transition from hospital to ambulatory care 1, 4

Common Pitfalls to Avoid

• Do not stop anticoagulation after 3 months in this patient with recurrent unprovoked VTE—this is a critical error that led to the current presentation 1, 5
• Do not use inferior vena cava filters routinely; they are not indicated for recurrent VTE on appropriate anticoagulation 1
• Do not delay resumption of anticoagulation due to recent hospitalization unless there was major surgery or active bleeding 1
• Do not assume the leg swelling is benign—always confirm or exclude DVT with objective testing 1

Special Considerations

If the recent hospitalization involved major surgery or trauma, this would classify the current event as "provoked," potentially allowing discontinuation after 3 months 1. However, given the history of prior unprovoked PE, indefinite anticoagulation would still be strongly favored 1.

The evidence overwhelmingly supports that this patient should never have stopped anticoagulation after the initial PE and must now resume it indefinitely. 1