What to do if an arterial clot occurs while on apixaban (Eliquis)?

Arterial Clot While on Apixaban: Management Approach

If an arterial clot occurs while on apixaban, immediately discontinue the medication and investigate for underlying causes of anticoagulation failure, including inappropriate dosing, drug interactions, or triple-positive antiphospholipid syndrome, while providing acute thrombosis management according to the specific arterial territory involved. 1

Immediate Actions

Discontinue Apixaban

• Stop apixaban immediately as the FDA boxed warning emphasizes that premature discontinuation increases thrombotic risk, but continuation during active arterial thrombosis represents anticoagulation failure. 1
• The half-life of apixaban is 6-15 hours with normal renal function, extending to 17 hours with severe renal impairment, which informs timing of alternative anticoagulation strategies. 2

Investigate Anticoagulation Failure

Assess for inappropriate dosing:

• Verify the patient is receiving the correct dose: 5 mg twice daily is standard for atrial fibrillation, but 2.5 mg twice daily is indicated only if the patient has at least 2 of the following: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1
• Underdosing is a common cause of thrombotic events during hospitalization, with one study showing all thromboembolic events occurred in underdosed patients. 2
• Common reasons for inappropriate underdosing include concurrent antiplatelet use, history of bleeding, frailty concerns, and fluctuating renal function. 2

Evaluate for drug interactions:

• Combined P-glycoprotein and strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's wort) reduce apixaban blood levels and should prompt avoidance of concomitant use. 1

Screen for triple-positive antiphospholipid syndrome:

• Apixaban is not recommended for patients with triple-positive antiphospholipid syndrome due to increased thrombosis risk. 1
• A randomized trial demonstrated that apixaban resulted in 6 strokes compared to 0 with warfarin in thrombotic antiphospholipid syndrome patients, leading to premature study termination. 3

Acute Thrombosis Management

Provide Territory-Specific Treatment

• Manage the arterial thrombosis according to the affected vascular territory (e.g., thrombolysis for acute stroke within appropriate time windows, revascularization for acute limb ischemia, percutaneous coronary intervention for myocardial infarction).
• Hemodynamic stabilization and supportive care are essential initial steps. 4

Transition to Alternative Anticoagulation

• Consider coverage with another anticoagulant as emphasized in the FDA boxed warning to reduce thrombotic risk when discontinuing apixaban. 1
• For patients with triple-positive antiphospholipid syndrome or confirmed thrombotic antiphospholipid syndrome, transition to warfarin with target INR 2-3, as this remains the standard of care. 3
• For other patients, options include transitioning to warfarin or investigating whether heparin bridging is appropriate depending on the clinical scenario.

Critical Pitfalls to Avoid

Do not assume the apixaban dose is correct without verification:

• Approximately 80% of inappropriate DOAC prescriptions are identified by pharmacists in hospital settings, highlighting the frequency of dosing errors. 2
• Overdosing can occur from continuation of home doses without adjusting for changing renal function or body weight. 2

Do not restart apixaban without addressing the underlying cause:

• If the patient was appropriately dosed and has no contraindications, the arterial thrombosis represents true anticoagulation failure.
• Prosthetic heart valves are an absolute contraindication to apixaban use. 1

Do not use apixaban in triple-positive antiphospholipid syndrome:

• The FDA specifically warns against use in this population due to increased thrombosis risk. 1
• The randomized trial evidence showing 6 arterial events (all strokes) with apixaban versus 0 with warfarin is compelling. 3