Would a patient on Eliquis (apixaban) receive tissue plasminogen activator (tPA) if an acute ischemic stroke occurs?

tPA Administration in Patients on Eliquis (Apixaban)

Patients on Eliquis (apixaban) should generally NOT receive tPA for acute ischemic stroke due to the high risk of bleeding complications, and mechanical thrombectomy should be pursued instead as the primary reperfusion strategy. 1

Current Guideline Recommendations

The 2015 Canadian Stroke Best Practice Recommendations explicitly state that tPA should not routinely be administered to patients on direct oral anticoagulants (DOACs) presenting with acute ischemic stroke until there is a commercially available and validated assessment tool for DOAC levels and reliable clinical interpretation of these levels. 1

Alternative Reperfusion Strategy

• Endovascular therapy (mechanical thrombectomy) may be considered in patients on DOACs like apixaban who present with acute ischemic stroke and large vessel occlusion. 1
• This approach avoids the compounded bleeding risk of combining systemic anticoagulation with thrombolytic therapy while still offering reperfusion treatment. 1

Rationale for Avoiding tPA in DOAC Patients

Bleeding Risk Considerations

• The combination of systemic anticoagulation with tPA carries a high risk of bleeding, particularly symptomatic intracranial hemorrhage. 1
• Patients on ECMO with systemic anticoagulation demonstrate that tPA in anticoagulated patients is generally not indicated due to bleeding risks, and this principle extends to DOAC-treated patients. 1
• The baseline symptomatic intracranial hemorrhage rate with tPA alone is approximately 4-6%, and this risk is substantially elevated in anticoagulated patients. 1, 2

Emerging Evidence on DOAC Patients

Recent observational data from 2018 suggests that among 492 NOAC patients who received tPA (including 40 on apixaban), the symptomatic intracranial hemorrhage rate was 4.3%, mortality was 11.3%, and favorable outcomes occurred in 43.7%. 3 However, these preliminary observations do not override current guideline recommendations against routine tPA use, as:

• Most patients (55.2%) had their last DOAC dose more than 12 hours before symptom onset, suggesting diminished anticoagulant effect. 3
• Few patients underwent sensitive laboratory testing to confirm anticoagulant levels before tPA administration. 3
• The study represents selected case reports and small series, not controlled trials. 3

Clinical Decision Algorithm

Step 1: Confirm Acute Ischemic Stroke

• Obtain non-contrast head CT immediately to exclude intracranial hemorrhage. 1
• Document time of symptom onset and last apixaban dose. 1

Step 2: Assess for Large Vessel Occlusion

• Obtain CT angiogram to identify large vessel occlusion. 1
• If large vessel occlusion is present, proceed directly to mechanical thrombectomy consultation. 1

Step 3: Consider Anticoagulant Status

• If patient is on apixaban, do NOT administer tPA as routine practice. 1
• There is no FDA-approved reversal agent for apixaban that would make tPA administration safer (unlike dabigatran, which has idarucizumab). 3

Step 4: Pursue Mechanical Thrombectomy

• Consult stroke specialists and neurointerventional team for mechanical thrombectomy if large vessel occlusion is confirmed. 1
• Mechanical thrombectomy should be pursued regardless of tPA eligibility in patients with large vessel occlusion. 1

Critical Pitfalls to Avoid

Do Not Delay Imaging

• Time is brain—obtain CT and CT angiogram emergently to determine if mechanical thrombectomy is an option. 1
• The window for mechanical thrombectomy extends beyond the tPA window in selected patients. 1

Do Not Assume Laboratory Testing Will Help

• Standard coagulation tests (PT/INR, aPTT) do not reliably measure apixaban levels and should not be used to guide tPA decisions. 1
• Anti-Xa assays specific for apixaban are not widely available in the acute setting. 3

Do Not Withhold All Reperfusion Therapy

• While tPA is contraindicated, mechanical thrombectomy remains a viable option and should be actively pursued. 1
• The presence of anticoagulation is not a contraindication to mechanical thrombectomy. 1

Special Circumstances

If Last Apixaban Dose Was >48 Hours Ago

• Even with extended time from last dose, current guidelines recommend against routine tPA use without validated anticoagulant level testing. 1
• The half-life of apixaban is approximately 12 hours, but individual pharmacokinetics vary, especially in patients with renal impairment. 3

If No Large Vessel Occlusion Present

• Aspirin therapy (160-325 mg) should be initiated after excluding intracranial hemorrhage, as this is recommended for acute ischemic stroke patients not receiving tPA. 1
• Continue to hold apixaban until bleeding risk is reassessed and secondary prevention strategy is determined. 1