Successful Thrombolytic Therapy With Recombinant Tissue Plasminogen Activator in Ischemic Stroke After Idarucizumab Administration for Reversal of Dabigatran

A Case Report

Toshiyuki Ohtani; Ryosuke Sintoku; Tasuku Yajima; Naoyuki Kaneko

Disclosures

J Med Case Reports. 2019;13(390) 

In This Article

Discussion

We report a case of a patient with acute lacunar stroke causing dysarthria and hemiparesis who was successfully treated by IVT therapy with rt-PA after reversal of dabigatran with idarucizumab.

DOACs have been increasingly used for stroke prevention in patients with NVAF. Dabigatran is one of the major DOACs acting as a direct thrombin inhibitor. Idarucizumab is a humanized monoclonal antibody fragment and is now available as the specific antidote that rapidly neutralizes the anticoagulant effect of dabigatran.[4] IVT therapy with rt-PA has been proposed after using idarucizumab in patients with acute ischemic stroke who are receiving dabigatran,[2,3] and a few articles have reported case studies and systematic reviews.[5–7] In a study that reviewed intravenous thrombolysis in stroke after dabigatran reversal with idarucizumab, 45 of 55 cases benefited from the treatment with a median NIHSS score improvement of 5, whereas unfavorable outcomes were observed in 6 patients (4 deaths, 2 patients with worsening of NIHSS scores, and 1 patient who developed another stroke 30 hours after the first IVT therapy).[7] In that review, in the available data of 37 patients, 56.76% of patients had grades 0–2 on the modified Rankin Scale at follow-up; hemorrhage extension occurred in 4 patients that ultimately resulted in 1 asymptomatic patient, 1 with severe disability, and 2 deaths. Thus, real-world data seem to indicate that this treatment is safe and effective.[7]

During administration of IVT therapy with rt-PA after reversal of dabigatran with idarucizumab, the possibilities of adverse events such as thrombosis and hemorrhage and deterioration in clinical condition need to be borne in mind. Some reports have described thrombotic complications such as deep vein thrombosis,[5] pulmonary embolism,[5] acute arterial occlusion of the right lower limb,[8] recurrence of ischemic stroke,[7,9] and cerebral edema.[7,10] Furthermore, extension of hemorrhage may cause fatal outcomes.[11,12] A report suggested that elderly Asian patients with higher NIHSS scores might be more susceptible to extension of hemorrhage.[12] However, these reports are still preliminary, and there are no data from large-scale clinical trials.

Consideration also needs to be given to the fact that the studies with positive data are more easily published than those with negative data. Large-scale trials on IVT therapy with rt-PA after reversal of dabigatran with idarucizumab in acute ischemic stroke should be carried out with regard to unfavorable outcomes such as thrombotic events, hemorrhagic transformation, and mortality to further explore potential concerns regarding safety and efficacy of this treatment.

In our patient's case, the significantly prolonged aPTT at the initial blood examination was immediately normalized, and the IVT therapy could be continued upon confirming dramatic reduction of the aPTT just after initiation of the rt-PA infusion, even though we had planned to terminate the IVT therapy if the aPTT was still prolonged.[3] We emphasize that, though this IVT therapy was carried out in an Asian woman just before the end of the recommended time limit, it was performed safely and resulted in a satisfactory outcome. We believe that this case report provides useful information regarding patients with acute ischemic stroke, including those with lacunar infarcts who are receiving dabigatran.

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