No Time to Lose: Cases of Anticoagulant Reversal Before Thrombolysis in Acute Ischemic Stroke Patients

Abstract

Direct oral anticoagulant (DOAC) reversal before intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients is well-documented in Europe, specifically for dabigatran: the selective humanized monoclonal antibody fragment idarucizumab, given to neutralize dabigatran prior to IVT, was associated with improved outcomes post-IVT. However, in the United States, this approach is rarely reported and not endorsed by guidelines. Therefore, further reporting on this is needed and neuroradiographic correlation may help validate this concept. At our hospital in Tampa, Florida, two octogenarians with atrial fibrillation, adherent with the DOAC dabigatran, presented with AIS shortly after symptom onset. Both received idarucizumab, then IVT. Clinical outcomes, treatment times, and perfusion-based neuroradiographic parameters were assessed. Patient A had a 41 ml penumbra on computed tomography perfusion (CTP) scan that decreased to 15 ml in final infarct volume on follow-up imaging, resulting in a 26 ml penumbral salvage (63.4%), and National Institutes of Health Stroke Scale (NIHSS) improved from 11 to 9 . Patient B had a 23 ml penumbra on CTP that decreased to 0.5 ml on follow-up imaging, resulting in a 22.5 ml penumbral salvage (97.8%), and NIHSS improved from 9 to 4. Neither developed bleeding complications. Both had delayed door-to-needle times but nevertheless demonstrated clinical neurological improvements. In our limited experience, IVT after immediate DOAC reversal in AIS patients on dabigatran was associated with clinical improvement in NIHSS by 2 to 5 points (with no neuroworsening), and penumbral salvage of ischemic brain tissue on neuroimaging ranging from 63.4% to 97.8%. Further reporting on this may lead to greater IVT use and better outcomes in "DOAC failures", especially for patients without other acute treatment options such as mechanical thrombectomy. Research into other anticoagulant reversal agents pre-IVT in AIS is also warranted.

Keywords: anticoagulation reversal; anticoagulation therapy; atrial fibrillation; ischemic stroke; thrombolytic.

Figure 1. Scans of Patient A

Patient A’s initial CT perfusion scan (top row) showed a moderate-sized 41 ml penumbra in a right MCA branch territory. The infarcted area is not visualized on the initial CT head (bottom row, left) while the final infarct in the right temporal region can be seen in the final CT scan (bottom row, middle). The final infarct volume corresponds to the Tmax > 10.0 s (bottom row, right) of 15 ml.

Figure 2. Scans of Patient B

Patient B’s initial CT perfusion scan (above) showed a moderate-sized 23 ml penumbra in a right MCA branch territory. However, MRI brain (below) revealed a final infarct volume of only 0.5 ml.