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Systemic Thrombolysis for Ischemic Stroke after Antagonizing Dabigatran with Idarucizumab—A Case Report
ARTICLE IN PRESS
Case Studies
Systemic Thrombolysis for Ischemic Stroke after Antagonizing Dabigatran with Idarucizumab—A Case Report Niklas Schäfer,
MD,*
Andreas Müller,
MD,†
and Ullrich Wüllner,
MD*
We here describe our experience of systemic thrombolysis therapy for severe ischemic stroke in a patient taking dabigatran for atrial fibrillation. After administration of the monoclonal antibody fragment idarucizumab, the anticoagulative effects of dabigatran were efficiently antagonized and application of alteplase was safe and feasible in our patient. This case report may illustrate a novel treatment option in the neurological emergency setting. Key Words: Idarucizumab—ischemic stroke—dabigatran—atrial fibrillation—systemic thrombolysis. © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Introduction The novel agent idarucizumab, a monoclonal antibody fragment, binds dabigatran within minutes and thereby offers an opportunity to efficiently reverse the anticoagulative effects of dabigatran.1,2 The interim results of the RE-VERSE AD clinical trial led to the approval of idarucizumab in the United States and in the European Union recently.
bleeding nor early signs of ischemic stroke (Fig 1, A). However, CT perfusion imaging showed “tissue at risk” (green overlay) in the dorsal territory of the right middle cerebral artery (MCA; Fig 1, B,C), and CT angiography revealed the corresponding occlusion of an M3 branch of the MCA. There were no exclusion criteria for systemic thrombolysis therapy but oral anticoagulation therapy with
Case Report We here describe our first experience with idarucizumab in emergency stroke treatment: A 67-year-old female was admitted to our hospital with a hemiparesis of the left side of the body. Onset was 90 minutes before admission and symptoms were severe with a total National Institute of Health Stroke score of 10 points. Computed tomography (CT) of the brain showed neither intracranial From the *Department of Neurology, University of Bonn Medical Center, Bonn, Germany; and †Department of Neuroradiology, University of Bonn Medical Center, Bonn, Germany. Received April 11, 2016; accepted May 3, 2016. Address correspondence to Niklas Schäfer, MD, Department of Neurology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, D-53127 Bonn, Germany. E-mail: [email protected]. 1052-3057/$ - see front matter © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.05.006
Figure 1. (A) Computed tomography at admission 90 minutes after symptom onset. (B and C) Computed tomography perfusion imaging showing decreased blood flow in the dorsal territory of the right middle cerebral artery (“tissue at risk” = green overlay). (D-F) Diffusion-weighted imaging displaying the infarction pattern.
Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2016: pp ■■–■■
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ARTICLE IN PRESS N. SCHÄFER ET AL.
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dabigatran (150 mg p.o. bid), which had been prescribed for permanent atrial fibrillation for 3 years and had been administered 4 hours before admission. Laboratory results showed the effect of dabigatran with a thrombin time of 130 seconds. We decided to use idarucizumab as an individual therapeutic approach with consent from the patient. Five minutes after the administration of 5 g idarucizumab, we initiated systemic intravenous thrombolysis with alteplase (6 mg injection bolus followed by 54 mg over 60 minutes). The final cerebral infarction pattern was probably attenuated by the systemic thrombolysis therapy, as magnetic resonance imaging revealed a smaller loss of tissue in the territory of the right MCA as expected from the CT perfusion imaging (Fig 1, D-F). Infarction occurred in the territory of the arteria choroidea anterior but not in the territory of the occluded M3 branch. No signs of hemorrhage were observed. Although the hemiparesis largely persisted, intensive physical treatment helped to improve the motor deficits.
Conclusion Antagonizing dabigatran with idarucizumab was feasible and safe in our patient. Idarucizumab may open novel treatment options in the emergency setting for patients taking dabigatran. This applies in particular to patients with ischemic stroke on oral anticoagulation with dabigatran, if they are eligible for systemic thrombolysis in general. Experience in ischemic stroke patients, however, is still scanty and therapeutic decisions for interventions must be taken carefully and well-balanced.
References 1. Glund S, Stangier J, Schmohl M, et al. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial. Lancet 2015;386:680-690. 2. Pollack CV Jr, Reilly PA, Eikelboom J, et al. Idarucizumab for dabigatran reversal. N Engl J Med 2015;373:511-520.
Case Studies
Systemic Thrombolysis for Ischemic Stroke after Antagonizing Dabigatran with Idarucizumab—A Case Report Niklas Schäfer,
MD,*
Andreas Müller,
MD,†
and Ullrich Wüllner,
MD*
We here describe our experience of systemic thrombolysis therapy for severe ischemic stroke in a patient taking dabigatran for atrial fibrillation. After administration of the monoclonal antibody fragment idarucizumab, the anticoagulative effects of dabigatran were efficiently antagonized and application of alteplase was safe and feasible in our patient. This case report may illustrate a novel treatment option in the neurological emergency setting. Key Words: Idarucizumab—ischemic stroke—dabigatran—atrial fibrillation—systemic thrombolysis. © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Introduction The novel agent idarucizumab, a monoclonal antibody fragment, binds dabigatran within minutes and thereby offers an opportunity to efficiently reverse the anticoagulative effects of dabigatran.1,2 The interim results of the RE-VERSE AD clinical trial led to the approval of idarucizumab in the United States and in the European Union recently.
bleeding nor early signs of ischemic stroke (Fig 1, A). However, CT perfusion imaging showed “tissue at risk” (green overlay) in the dorsal territory of the right middle cerebral artery (MCA; Fig 1, B,C), and CT angiography revealed the corresponding occlusion of an M3 branch of the MCA. There were no exclusion criteria for systemic thrombolysis therapy but oral anticoagulation therapy with
Case Report We here describe our first experience with idarucizumab in emergency stroke treatment: A 67-year-old female was admitted to our hospital with a hemiparesis of the left side of the body. Onset was 90 minutes before admission and symptoms were severe with a total National Institute of Health Stroke score of 10 points. Computed tomography (CT) of the brain showed neither intracranial From the *Department of Neurology, University of Bonn Medical Center, Bonn, Germany; and †Department of Neuroradiology, University of Bonn Medical Center, Bonn, Germany. Received April 11, 2016; accepted May 3, 2016. Address correspondence to Niklas Schäfer, MD, Department of Neurology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, D-53127 Bonn, Germany. E-mail: [email protected]. 1052-3057/$ - see front matter © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.05.006
Figure 1. (A) Computed tomography at admission 90 minutes after symptom onset. (B and C) Computed tomography perfusion imaging showing decreased blood flow in the dorsal territory of the right middle cerebral artery (“tissue at risk” = green overlay). (D-F) Diffusion-weighted imaging displaying the infarction pattern.
Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2016: pp ■■–■■
1
ARTICLE IN PRESS N. SCHÄFER ET AL.
2
dabigatran (150 mg p.o. bid), which had been prescribed for permanent atrial fibrillation for 3 years and had been administered 4 hours before admission. Laboratory results showed the effect of dabigatran with a thrombin time of 130 seconds. We decided to use idarucizumab as an individual therapeutic approach with consent from the patient. Five minutes after the administration of 5 g idarucizumab, we initiated systemic intravenous thrombolysis with alteplase (6 mg injection bolus followed by 54 mg over 60 minutes). The final cerebral infarction pattern was probably attenuated by the systemic thrombolysis therapy, as magnetic resonance imaging revealed a smaller loss of tissue in the territory of the right MCA as expected from the CT perfusion imaging (Fig 1, D-F). Infarction occurred in the territory of the arteria choroidea anterior but not in the territory of the occluded M3 branch. No signs of hemorrhage were observed. Although the hemiparesis largely persisted, intensive physical treatment helped to improve the motor deficits.
Conclusion Antagonizing dabigatran with idarucizumab was feasible and safe in our patient. Idarucizumab may open novel treatment options in the emergency setting for patients taking dabigatran. This applies in particular to patients with ischemic stroke on oral anticoagulation with dabigatran, if they are eligible for systemic thrombolysis in general. Experience in ischemic stroke patients, however, is still scanty and therapeutic decisions for interventions must be taken carefully and well-balanced.
References 1. Glund S, Stangier J, Schmohl M, et al. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial. Lancet 2015;386:680-690. 2. Pollack CV Jr, Reilly PA, Eikelboom J, et al. Idarucizumab for dabigatran reversal. N Engl J Med 2015;373:511-520.