G Model
ARTICLE IN PRESS
CLINEU-3675; No. of Pages 2
Clinical Neurology and Neurosurgery xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Letter to the Editor Intravenous thrombolysis with recombinant tissue plasminogen activator for acute ischemic stroke in a patient treated with rivaroxaban Keywords: Acute stroke Stroke therapy Thrombolytic therapy
Dear Editor, Intravenous recombinant tissue plasminogen activator (IV rtPA) is the only approved therapy for acute ischemic stroke [1]. International guidelines stipulate that anticoagulant use is a (relative) contraindication for treatment with IV rtPA. Rivaroxaban is an oral direct factor Xa inhibitor that is increasingly being used in routine clinical practice for primary prevention and treatment of venous thromboembolism, stroke prevention in nonvalvular atrial fibrillation and only in Europe as secondary prevention in acute coronary syndromes [2]. It is therefore expected that clinicians will be increasingly confronted with the question how to treat acute ischemic stroke in these patients [3]. Data on the bleeding risk in patients treated with IV rtPA while taking rivaroxaban are lacking. Various commercial assays have been developed to measure the drug concentration, but as these are not yet widely available bedside [4], the prothrombin time (PT) is suggested as a limited alternative to assess the presence of anticoagulant effect, especially in urgent situations [5].
We report the case of an 80 year old male right-handed patient presenting with a global aphasia, conjugated eye deviation and head rotation to the left, complete right hemianopsia, severe right hemicorporal sensory loss and paralysis (National Institutes of Health Stroke Scale score, NIHSS, 19). The patient was taking rivaroxaban 20 mg once daily since several weeks for paroxysmal atrial fibrillation and recent pulmonary emboli. The last drug intake was 24 h before presentation. The non-contrast computed tomography (CT) scan showed the presence of a left insular ribbon sign (Fig. 1A) and a ‘dot sign’ in the M2 segment of the left middle cerebral artery; the latter could be confirmed by reconstruction images of the perfusion acquisition (Fig. 1B). Perfusion-CT demonstrated an important hypoperfusion of the territory of the left middle cerebral artery, mainly consisting of a large area of ischemic penumbra (prolonged Tmax) and a relatively small ischemic core (decreased CBV) (Fig. 1C). The platelet count was 364 × 109 /L (normal: 158–450 × 109 /L), PT was 44% (normal: >70%), the International Normalized Ratio was 1.8 (normal: 0.8–1.3), fibrinogen was 359 mg/dL (normal: 180–400 mg/dL) and the activated partial thromboplastin time was 29.4 s (normal: 22.2–34.4 s). Renal function was within normal limits. Treatment with intravenous thrombolysis was initiated 135 min after stroke onset after informed consent was obtained by proxy. Except for mild and self-limiting hematuria, no complications occurred. The patient gradually improved after administration of IV rtPA (NIHSS at 24 h after symptom onset: 8), with persisting motor aphasia. Control CT scan of the brain showed an infarction confined to the left subinsular region with hemorrhagic transformation compatible with the ischemic core lesion on perfusion
Fig. 1. (A) Non contrast CT scan revealing a left sided insular ribbon sign (closed arrow). (B) 35 mm MIP reconstruction of CT perfusion data showing a lower and irregular enhancement of the left MCA with thrombosis defects (open arrow). (C) CT perfusion calculated map, based on the Tmax and CBV, showing the small core lesion (red) in the subinsular region and the important penumbra (blue) in the region of the left MCA. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.) http://dx.doi.org/10.1016/j.clineuro.2013.12.029 0303-8467/© 2014 Elsevier B.V. All rights reserved.
Please cite this article in press as: van Hooff R-J, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute ischemic stroke in a patient treated with rivaroxaban. Clin Neurol Neurosurg (2014), http://dx.doi.org/10.1016/j.clineuro.2013.12.029
G Model CLINEU-3675; No. of Pages 2
ARTICLE IN PRESS Letter to the Editor / Clinical Neurology and Neurosurgery xxx (2014) xxx–xxx
2
images. Transcranial ultrasound 2 days after stroke demonstrated reperfusion of the left middle cerebral artery. This case underlines the need for further studies on the safety of intravenous thrombolysis in patients taking rivaroxaban. Prospective registration of similar cases in an (international) database is of highly added value. Conflicts of interest The authors state that there are no conflicts of interest. References [1] Adams Jr HP, del Zoppo G, Alberts MJ, Bhatt DL, Brass L, Furlan A, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke 2007;38:1655–711. [2] Cove CL, Hylek EM. An updated review of target-specific oral anticoagulants used in stroke prevention in atrial fibrillation, venous thromboembolic disease, and acute coronary syndromes. J Am Heart Assoc 2013;2:e000136. [3] Dempfle CE, Hennerici MG. Fibrinolyitc treatment of acute ischemic stroke for patients on new oral anticoagulant drugs. Cerebrovasc Dis 2011;32(6): 616–9. [4] Steiner T, Böhm M, Dichgans M, Diener HC, Ell C, Endres M, et al. Recommendations for the emergency management of complications associated with the new direct oral anticoagulants (DOACs), apixaban, dabigatran and rivaroxaban. Clin Res Cardiol 2013 Jun;102(6):399–412. [5] Samama MM, Contant G, Spiro TE, Perzborn E, Le Flem L, Guinet C, et al. Laboratory assessment of rivaroxaban: a review. Thromb J 2013;11:11.
Ann De Smedt Department of Neurology, Universitair Ziekenhuis Brussel, Brussels, Belgium Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Brussels, Belgium Laetitia Yperzeele Department of Neurology, Universitair Ziekenhuis Brussel, Brussels, Belgium Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Brussels, Belgium Kristin Jochmans Department of Haematology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium Jacques De Keyser a,b Department of Neurology, Universitair Ziekenhuis Brussel, Brussels, Belgium Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Brussels, Belgium b Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
a
Raf Brouns Department of Neurology, Universitair Ziekenhuis Brussel, Brussels, Belgium Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Brussels, Belgium ∗ Corresponding
Robbert-Jan van Hooff ∗ Department of Neurology, Universitair Ziekenhuis Brussel, Brussels, Belgium Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Brussels, Belgium
author at: Department of Neurology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Brussel, Belgium. Tel.: +32 2 4776410; fax: +32 2 4776800. E-mail address: [email protected] (R.-J. van Hooff)
Koenraad Nieboer Department of Radiology, Universitair Ziekenhuis Brussel, Brussels, Belgium
23 November 2013 Available online xxx
Please cite this article in press as: van Hooff R-J, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute ischemic stroke in a patient treated with rivaroxaban. Clin Neurol Neurosurg (2014), http://dx.doi.org/10.1016/j.clineuro.2013.12.029
ARTICLE IN PRESS
CLINEU-3675; No. of Pages 2
Clinical Neurology and Neurosurgery xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Letter to the Editor Intravenous thrombolysis with recombinant tissue plasminogen activator for acute ischemic stroke in a patient treated with rivaroxaban Keywords: Acute stroke Stroke therapy Thrombolytic therapy
Dear Editor, Intravenous recombinant tissue plasminogen activator (IV rtPA) is the only approved therapy for acute ischemic stroke [1]. International guidelines stipulate that anticoagulant use is a (relative) contraindication for treatment with IV rtPA. Rivaroxaban is an oral direct factor Xa inhibitor that is increasingly being used in routine clinical practice for primary prevention and treatment of venous thromboembolism, stroke prevention in nonvalvular atrial fibrillation and only in Europe as secondary prevention in acute coronary syndromes [2]. It is therefore expected that clinicians will be increasingly confronted with the question how to treat acute ischemic stroke in these patients [3]. Data on the bleeding risk in patients treated with IV rtPA while taking rivaroxaban are lacking. Various commercial assays have been developed to measure the drug concentration, but as these are not yet widely available bedside [4], the prothrombin time (PT) is suggested as a limited alternative to assess the presence of anticoagulant effect, especially in urgent situations [5].
We report the case of an 80 year old male right-handed patient presenting with a global aphasia, conjugated eye deviation and head rotation to the left, complete right hemianopsia, severe right hemicorporal sensory loss and paralysis (National Institutes of Health Stroke Scale score, NIHSS, 19). The patient was taking rivaroxaban 20 mg once daily since several weeks for paroxysmal atrial fibrillation and recent pulmonary emboli. The last drug intake was 24 h before presentation. The non-contrast computed tomography (CT) scan showed the presence of a left insular ribbon sign (Fig. 1A) and a ‘dot sign’ in the M2 segment of the left middle cerebral artery; the latter could be confirmed by reconstruction images of the perfusion acquisition (Fig. 1B). Perfusion-CT demonstrated an important hypoperfusion of the territory of the left middle cerebral artery, mainly consisting of a large area of ischemic penumbra (prolonged Tmax) and a relatively small ischemic core (decreased CBV) (Fig. 1C). The platelet count was 364 × 109 /L (normal: 158–450 × 109 /L), PT was 44% (normal: >70%), the International Normalized Ratio was 1.8 (normal: 0.8–1.3), fibrinogen was 359 mg/dL (normal: 180–400 mg/dL) and the activated partial thromboplastin time was 29.4 s (normal: 22.2–34.4 s). Renal function was within normal limits. Treatment with intravenous thrombolysis was initiated 135 min after stroke onset after informed consent was obtained by proxy. Except for mild and self-limiting hematuria, no complications occurred. The patient gradually improved after administration of IV rtPA (NIHSS at 24 h after symptom onset: 8), with persisting motor aphasia. Control CT scan of the brain showed an infarction confined to the left subinsular region with hemorrhagic transformation compatible with the ischemic core lesion on perfusion
Fig. 1. (A) Non contrast CT scan revealing a left sided insular ribbon sign (closed arrow). (B) 35 mm MIP reconstruction of CT perfusion data showing a lower and irregular enhancement of the left MCA with thrombosis defects (open arrow). (C) CT perfusion calculated map, based on the Tmax and CBV, showing the small core lesion (red) in the subinsular region and the important penumbra (blue) in the region of the left MCA. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.) http://dx.doi.org/10.1016/j.clineuro.2013.12.029 0303-8467/© 2014 Elsevier B.V. All rights reserved.
Please cite this article in press as: van Hooff R-J, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute ischemic stroke in a patient treated with rivaroxaban. Clin Neurol Neurosurg (2014), http://dx.doi.org/10.1016/j.clineuro.2013.12.029
G Model CLINEU-3675; No. of Pages 2
ARTICLE IN PRESS Letter to the Editor / Clinical Neurology and Neurosurgery xxx (2014) xxx–xxx
2
images. Transcranial ultrasound 2 days after stroke demonstrated reperfusion of the left middle cerebral artery. This case underlines the need for further studies on the safety of intravenous thrombolysis in patients taking rivaroxaban. Prospective registration of similar cases in an (international) database is of highly added value. Conflicts of interest The authors state that there are no conflicts of interest. References [1] Adams Jr HP, del Zoppo G, Alberts MJ, Bhatt DL, Brass L, Furlan A, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke 2007;38:1655–711. [2] Cove CL, Hylek EM. An updated review of target-specific oral anticoagulants used in stroke prevention in atrial fibrillation, venous thromboembolic disease, and acute coronary syndromes. J Am Heart Assoc 2013;2:e000136. [3] Dempfle CE, Hennerici MG. Fibrinolyitc treatment of acute ischemic stroke for patients on new oral anticoagulant drugs. Cerebrovasc Dis 2011;32(6): 616–9. [4] Steiner T, Böhm M, Dichgans M, Diener HC, Ell C, Endres M, et al. Recommendations for the emergency management of complications associated with the new direct oral anticoagulants (DOACs), apixaban, dabigatran and rivaroxaban. Clin Res Cardiol 2013 Jun;102(6):399–412. [5] Samama MM, Contant G, Spiro TE, Perzborn E, Le Flem L, Guinet C, et al. Laboratory assessment of rivaroxaban: a review. Thromb J 2013;11:11.
Ann De Smedt Department of Neurology, Universitair Ziekenhuis Brussel, Brussels, Belgium Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Brussels, Belgium Laetitia Yperzeele Department of Neurology, Universitair Ziekenhuis Brussel, Brussels, Belgium Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Brussels, Belgium Kristin Jochmans Department of Haematology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium Jacques De Keyser a,b Department of Neurology, Universitair Ziekenhuis Brussel, Brussels, Belgium Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Brussels, Belgium b Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
a
Raf Brouns Department of Neurology, Universitair Ziekenhuis Brussel, Brussels, Belgium Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Brussels, Belgium ∗ Corresponding
Robbert-Jan van Hooff ∗ Department of Neurology, Universitair Ziekenhuis Brussel, Brussels, Belgium Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Brussels, Belgium
author at: Department of Neurology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Brussel, Belgium. Tel.: +32 2 4776410; fax: +32 2 4776800. E-mail address: [email protected] (R.-J. van Hooff)
Koenraad Nieboer Department of Radiology, Universitair Ziekenhuis Brussel, Brussels, Belgium
23 November 2013 Available online xxx
Please cite this article in press as: van Hooff R-J, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute ischemic stroke in a patient treated with rivaroxaban. Clin Neurol Neurosurg (2014), http://dx.doi.org/10.1016/j.clineuro.2013.12.029
