Acute Stroke Treatment in an Anticoagulated Patient: When Is Thrombolysis an Option?

Abstract

Purpose of Review Direct oral anticoagulants (DOACs: the factor Xa inhibitors rivaroxaban, apixaban, and edoxaban and the direct thrombin inhibitor dabigatran) are the mainstay of stroke prevention in patients with non-valvular atrial fibrillation (AF). Nevertheless, there is a residual stroke risk of 1–2% per year despite DOAC therapy. Intravenous thrombolysis (IVT) reduces morbidity in patients with ischemic stroke and improves functional outcome. Prior DOAC therapy is a (relative) contraindication for IVT but emerging evidence supports its use in selected patients. Recent Findings Recent observational studies highlighted that IVT in patients on prior DOAC therapy seems feasible and did not yield major safety issues. Different selection criteria and approaches have been studied including selection by DOAC plasma levels, non-specific coagulation assays, time since last intake, and prior reversal agent use. The optimal selection process is however not clear and most studies comprised few patients. Summary IVT in patients taking DOAC is a clinically challenging scenario. Several approaches have been proposed without major safety issues but current evidence is weak. A patient-oriented approach balancing potential benefits of IVT (i.e., amount of salvageable penumbra) against expected bleeding risk including appropriate monitoring of anticoagulant activity seem justified.

Point-of-Care Assessment of Direct Oral Anticoagulation in Acute Ischemic Stroke: Protocol for a Prospective Observational Diagnostic Accuracy Study

“…Viscoelastic POC quantification of coagulation time in the whole blood might pose a shift toward personalized medicine in the hyperacute decision-making on IVT in stroke patients. While it is commonly accepted to perform IVT in patients who have not taken any DOAC over the past 48 hours, [21][22][23] exceptions to this rule of thumb might apply where pharmacokinetic characteristics are altered due to hepatic or renal conditions, advanced age, or drug interactions with cytochrome P450 isoenzymes or P-glycoprotein. 55 Moreover, the results of this study will have implications to the management of patients suffering from acute intracerebral hemorrhage as well, where timely knowledge on the presence of clinically significant levels of anticoagulation can allow targeted antagonization.…”

“…Viscoelastic POC quantification of coagulation time in the whole blood might pose a shift toward personalized medicine in the hyperacute decision-making on IVT in stroke patients. While it is commonly accepted to perform IVT in patients who have not taken any DOAC over the past 48 hours, 21 22 23 exceptions to this rule of thumb might apply where pharmacokinetic characteristics are altered due to hepatic or renal conditions, advanced age, or drug interactions with cytochrome P450 isoenzymes or P-glycoprotein. 55 …”

“…Delivery of IVT after at least 48 hours from last DOAC intake is widely accepted as safe based on the pharmacodynamic and pharmacokinetic profiles of these substances. 21 22 23 However, this may lead to the exclusion of AIS patients who would still benefit from IVT without compromising safety of treatment as indicated by a recent meta-analysis that synthesized data from 52,823 AIS patients. 24 Furthermore, that information is not readily available in the acute setting.…”

Association Between Plasma Anti-Factor Xa Concentrations and Large Artery Occlusion in Patients With Acute Ischemic Stroke Taking Direct Oral Anticoagulants for Non-valvular Atrial Fibrillation

“…The DOAC activities were categorized as “low” (<100 ng/mL) or “high” (≥100 ng/mL). A plasma DOAC concentration of ≤100 ng/mL was previously recommended as a threshold for using thrombolytics to treat AIS based on theoretical and pharmacological data [ 6 , 7 ]. This study was approved by the Institutional Review Board of Dong-A University Hospital, Busan, Korea (approval number DAUHIRB-21- 019).…”