Intravenous recombinant human tissue plasminogen activator for ischemic stroke treatment

A controlled before-after study showed the beneficial effects of intravenous thrombolytic treatment in patients with moderate to severe acute ischemic stroke. A retrospective study with low methodological quality reported the improved vocational outcome of an outpatient rehabilitation program in patients with mild to moderate ischaemic stroke. There currently is insufficient evidence regarding the effectiveness of interventions to promote return-to-work in patients with ischaemic stroke, though intravenous thrombolytic therapy has shown beneficial effects and there are indications that rehabilitation programs may also be advantageous ¹⁾.

Recombinant human tissue plasminogen activator (tPA) is the effective drug for the treatment of acute ischemic stroke. In addition to thrombolysis, tPA is also involved in neuroplasticity.However, tPA has potential adverse side effects when administered intravenously including brain edema and hemorrhage.

Whether intravenous recombinant tissue plasminogen activator (r-TPA) therapy can be administered in acute ischemic stroke patients treated with novel oral anticoagulants (NOACs), including rivaroxaban, remains controversial.

A 76-year-old woman with nonvalvular atrial fibrillation, who had been receiving 15 mg rivaroxaban once daily, was brought to the emergency department with right-side hemiparesis and aphasia. The onset of neurological deficits occurred 8 hours after the last dose of rivaroxaban administration.

The patient was diagnosed with acute ischemic stroke.

Intravenous infusion of 0.6 mg/kg of r-TPA (total dose: 29 mg) was performed 9 hours and 40 minutes after the last rivaroxaban administration. During r-TPA infusion, improvement in the patient's neurological deficit was observed.

The clinical picture evidently improved from with National Institutes of Health Stroke Scale 21 to 16 on completion of r-TPA treatment.

Although current guidelines do not recommend administering thrombolytics in patients using NOACs with a doubtful anticoagulation status and administered within the last 24 or, even more strictly, 48 hours, this and other case studies suggest that r-TPA treatment could be considered in selected acute ischemic stroke patients receiving rivaroxaban or other Xa inhibitors, taking the patient's clinical condition and the prospective clinical benefits of r-TPA into account ²⁾.

The target time for IV tPA administration (“door to needle time”) is within 60 minutes from time of arrival to hospital. However, IV tPA can be administered up to 4.5 hours after the onset of symptoms if the patient does not have any contraindications ³⁾.

Dose: 0.9 mg/kg (max 90 mg) with 10% of the dose administered as a bolus over 1 minute and the rest infused over 60 minutes.