Acute Ischemic Stroke Management in Patients Receiving Anticoagulation

Immediate Assessment

Determine the timing of the last dose of a direct oral anticoagulant; doses taken within 48 hours are considered recent and influence reperfusion decisions【1】.

If the INR is ≤ 1.7, intravenous alteplase may be administered【2】.
If the INR is > 1.7, thrombolysis is contraindicated even after reversal with vitamin K or prothrombin complex concentrates【2】.
The INR 1.7 threshold is absolute; attempting reversal to enable thrombolysis above this level is not recommended because it may increase thrombotic risk without proven benefit【1】.

Anti‑Xa agents (apixaban, rivaroxaban, edoxaban) – when plasma concentration is < 50 ng/mL, thrombolysis may be given【1】.
Anti‑Xa agents – with concentrations 50–100 ng/mL, thrombolysis can be considered on a case‑by‑case basis, weighing stroke severity against bleeding risk【1】.
Anti‑Xa agents – at ≥ 100 ng/mL, thrombolysis is contraindicated【1】.
Dabigatran – if the plasma level is < 50 ng/mL or thrombin time is < 60 seconds, thrombolysis may be performed【1】.
Dabigatran – with levels 50–100 ng/mL, thrombolysis may be considered individually【1】.
Dabigatran – at ≥ 100 ng/mL, thrombolysis is contraindicated【1】.
For dabigatran‑treated patients, administration of idarucizumab 5 g IV for reversal followed by thrombolysis is an accepted strategy【1】.
General DOAC guidance when plasma levels are unavailable – the 2018 AHA/ASA guideline advises that alteplase should not be given to patients who have received therapeutic DOAC doses within the preceding 48 hours unless specific testing confirms safety【3】.
Prohibited adjuncts – prothrombin complex concentrates and andexanet alfa should not be used to facilitate thrombolysis in DOAC‑treated patients because they increase thrombotic risk without clear benefit【1】.

Intravenous thrombolysis is contraindicated in patients receiving therapeutic UFH, LMWH, or fondaparinux【1】.
No guideline recommendation exists for using protamine sulfate reversal before thrombolysis in UFH‑treated patients【2】.

For all patients with proximal large‑vessel occlusion, mechanical thrombectomy should be performed regardless of anticoagulation status or prior thrombolysis【1】 (Grade 1+, strong agreement).
Thrombectomy carries a lower risk of symptomatic intracranial hemorrhage compared with IV thrombolysis in anticoagulated patients【1】.

Maintain systolic/diastolic blood pressure < 180/105 mmHg for at least 24 hours following alteplase administration【3】.
This blood‑pressure target applies irrespective of prior anticoagulation【3】.

Oral anticoagulation may be re‑initiated within 2 weeks of an acute ischemic stroke; the exact optimal timing remains uncertain【5】.
Bridging with heparinoids (UFH, LMWH, fondaparinux) in the first 48 hours after stroke should be avoided because it increases symptomatic intracranial hemorrhage without net benefit【5】.