Yes, Intravenous Thrombolysis Should Be Administered in Pregnancy When Other Clinical and Imaging Factors Are Favorable
2013; Lippincott Williams & Wilkins; Volume: 44; Issue: 3 Linguagem: Inglês
10.1161/strokeaha.111.000134
ISSN1524-4628
Autores Tópico(s)Acute Ischemic Stroke Management
ResumoHomeStrokeVol. 44, No. 3Yes, Intravenous Thrombolysis Should Be Administered in Pregnancy When Other Clinical and Imaging Factors Are Favorable Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBYes, Intravenous Thrombolysis Should Be Administered in Pregnancy When Other Clinical and Imaging Factors Are Favorable Andrew M. Demchuk, MD, FRCPC Andrew M. DemchukAndrew M. Demchuk From the Calgary Stroke Program, Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Alberta, Canada. Originally published7 Feb 2013https://doi.org/10.1161/STROKEAHA.111.000134Stroke. 2013;44:864–865Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2013: Previous Version 1 Acute stroke treatment decision-making is a complex process that must be performed quickly. In each case, we must balance the potential benefits with the relevant risks of each therapy to our patients. In this case, the major challenge is determining whether systemic tPA (tissue plasminogen activator) or endovascular treatment is more appropriate in pregnancy.Pregnancy has historically been regarded as a contraindication to IV tPA treatment. Yet tPA is not known to be teratogenic and tPA is also too large a molecule to cross the placenta. To date, 8 cases have been published of IV tPA treatment in pregnancy with only 1 mother suffering a significant uterine bleeding complication and most achieving a good neurological recovery.1,2 Maternal hemorrhagic complications have been reported in 8% with systemic thrombolysis across the spectrum of clinical thromboembolic indications.3 Overall, the IV tPA risk seems reasonably low in pregnancy and not considered an absolute contraindication. This low risk during pregnancy must be balanced against the potential of a disabled outcome without treatment. Although pregnancy is a key determinant of this decision-making process, other clinical and radiological factors should also play a significant role in the art of acute stroke treatment decision-making.These clinical and radiological factors relevant in this particular case include age, stroke severity, MR-mismatch, and occlusion site. The risk of IV tPA-related symptomatic intracerebral hemorrhage is quite low in young individuals. In fact, in over 2700 subjects treated with IV tPA with <60 years, the symptomatic intracerebral hemorrhage rate was only 2.8%, roughly half the overall symptomatic intracerebral hemorrhage risk across all ages.4 Stroke severity of baseline National Institute of Health Stroke Scale of 12 is consistent with a moderate stroke, which is sufficiently disabling to warrant consideration of systemic tPA treatment. The imaging factor of a diffusion-weighted imaging (DWI)/perfusion-weighted imaging mismatch may also be favorable for systemic thrombolysis. Mismatch suggests some salvageable tissue at risk that would benefit from successful recanalization. DWI/perfusion-weighted imaging mismatch requires more description because its meaning depends on the specific perfusion parameters used to define perfusion-weighted imaging (ie, Tmax delay of 6 seconds versus other)5 and ischemic core (ie, DWI lesion versus apparent diffusion coefficient values <550×10−9 mm/s2). The most crucial information from the magnetic resonance imaging may be the baseline volume of the ischemic core measured by the DWI lesion. In the Echoplanar Imaging Thrombolytic Evaluation trial, baseline DWI lesions <18 mL had a remarkably low number needed to treat of only 1.8 for IV rtPA (3–6 hours from onset) compared with placebo (77% versus 18% placebo; odds ratio, 15.0; P<0.001).6 A very small baseline DWI lesion would certainly support a role for systemic thrombolysis in this patient.One underappreciated factor that must be considered when deciding between IV tPA and endovascular treatment is the location of the intracranial occlusion. An M2 middle cerebral artery occlusion is associated with at least moderate rates of early recanalization with systemic tPA.7 The main difficulty with endovascular treatment is the complete absence of any randomized clinical trial data supporting superiority of such treatment in such M2 middle cerebral artery occlusions compared with IV tPA. It remains very unclear whether endovascular treatment provides much of any advantage over IV tPA in such distal occlusions, especially given the delays typical of such an intervention after symptom onset and the additional risk required to navigate to and engage the thrombus in such locations with these large diameter devices. A reasonable assumption is that further distal the occlusion the less likely endovascular treatment will outperform standard IV tPA treatment. It is also possible that vascular wall changes common in pregnancy could increase risks of vascular wall injury with such devices.8 Theoretically, endovascular treatment with mechanical thrombectomy devices should limit any systemic bleeding risk if only a mechanical device is used and intraarterial tPA avoided. However, there remains no reported experience on use of these devices during pregnancy.So should we administer IV thrombolysis in pregnancy and more specifically, in this pregnant patient? I say yes because the risk is low and the likelihood of benefit from IV tPA significant, given the presence of a distal occlusion (M2 middle cerebral artery) and MR-mismatch. If the patient is treated at a primary stroke center, I would initiate systemic therapy, but I would also transport that patient quickly to a tertiary care center/comprehensive stroke center as a drip and ship. This would offer 2 advantages. First, in case of maternal or fetal complication, the patient/fetus would have the most advanced technology and expertize available for fetal and maternal care within the neonatal intensive care unit advanced obstetric unit. Second, the neuroendovascular suite with the numerous options of mechanical thrombectomy would at least provide rescue or bridging options if no neurological improvement or worsening is seen during transport. A similar strategy could be applied if the patient is first transported directly to the comprehensive stroke center. With obstetric back-up, IV tPA should be administered followed by bridging endovascular therapy in situations where no clinical improvement seen.DisclosuresDr Demchuk receives salary support from Alberta Innovates Health Solutions. He is also supported by a Stroke Foundation Chair in Stroke Research.The Case:A 37-year-old woman, gravida 2, para 0, 22 weeks pregnant, presents within 90 minutes of abrupt onset of global aphasia and right-sided hemiparesis (NIHSS score 12). MRA shows left M2 occlusion. MRI shows ipsilateral DWI/PWI mismatch.The Questions:Should she be considered for treatment with intravenous t-PA?If no, should the patient receive endovascular therapy: IA t-PA, mechanical thrombectomy, or both?The Controversy:Should thrombolysis be considered in pregnant women with acute stroke?FootnotesStroke welcomes eComments on Controversies in Stroke. This exciting feature allows for the rapid online appearance of appropriate comments related to content in the Controversies in Stroke section. All comments are reviewed by the editors, who will decide on their acceptability. For those interested in participating, please go to the Controversy that you wish to comment on and select the link to Submit a Comment (in the right hand column under Comments).The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. This article is Part 1 of a 3-part article. Parts 2 and 3 appear on pages 866 and 868, respectively.Correspondence to Andrew M. Demchuk, MD, FRCPC, Foothills Medical Center, 1403 29 St NW, Calgary, Alberta, Canada T2N 2T9. E-mail [email protected]References1. Yamaguchi Y, Kondo T, Ihara M, Kawamata J, Fukuyama H, Takahashi R. Intravenous recombinant tissue plasminogen activator in an 18-week pregnant woman with embolic stroke.Rinsho Shinkeigaku. 2010; 50:315–319.CrossrefMedlineGoogle Scholar2. Tassi R, Acampa M, Marotta G, Cioni S, Guideri F, Rossi S, et al. Systemic thrombolysis for stroke in pregnancy.Am J Emerg Med; August 6, 2012. DOI: 10.1016/j.ajem.2012.05.040. http://www.ajemjournal.com/article/S0735-6757(12)00269-0/fulltext.MedlineGoogle Scholar3. Cronin CA, Weisman CJ, Llinas RH. Stroke treatment: beyond the three-hour window and in the pregnant patient.Ann N Y Acad Sci. 2008; 1142:159–178.CrossrefMedlineGoogle Scholar4. Menon BK, Saver JL, Prabhakaran S, Reeves M, Liang L, Olson DM, et al. Risk score for intracranial hemorrhage in patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator.Stroke. 2012; 43:2293–2299.LinkGoogle Scholar5. Olivot JM, Mlynash M, Thijs VN, Kemp S, Lansberg MG, Wechsler L, et al. Optimal Tmax threshold for predicting penumbral tissue in acute stroke.Stroke. 2009; 40:469–475.LinkGoogle Scholar6. Parsons MW, Christensen S, McElduff P, Levi CR, Butcher KS, De Silva DA, et al; Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) Investigators. Pretreatment diffusion- and perfusion-MR lesion volumes have a crucial influence on clinical response to stroke thrombolysis.J Cereb Blood Flow Metab. 2010; 30:1214–1225.CrossrefMedlineGoogle Scholar7. Saqqur M, Uchino K, Demchuk AM, Molina CA, Garami Z, Calleja S, et al; CLOTBUST Investigators. Site of arterial occlusion identified by transcranial Doppler predicts the response to intravenous thrombolysis for stroke.Stroke. 2007; 38:948–954.LinkGoogle Scholar8. Akhter T, Larsson A, Larsson M, Wikstrom AK, Naessen T. Artery wall layer dimensions during normal pregnancy- a longitudinal study using non-invasive high-frequency ultrasound.Am J Physiol Heart Circ Physiol. 2013; 304:H229–234.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Bojda M, Cimprichová A, Vavríková B, Filipková A and Gdovinová Z (2021) Intravenous thrombolysis for stroke in pregnancy should be administered if the benefit outweighs the risk: A case report and recommended diagnostic workup, Women's Health, 10.1177/1745506521999495, 17, (174550652199949), Online publication date: 1-Jan-2021. Uy C, Gosselin-Lefebvre S, Book A and Field T (2020) Reperfusion Therapy for Acute Stroke in Pregnant and Post-Partum Women: A Canadian Survey, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 10.1017/cjn.2020.207, 48:3, (344-348), Online publication date: 1-May-2021. Buscher M and Edwards J (2020) Obstetric Emergency Critical Care Emergency Department Critical Care, 10.1007/978-3-030-28794-8_30, (503-532), . Singhal V (2020) Management in a Patient with Stroke Problem Based Learning Discussions in Neuroanesthesia and Neurocritical Care, 10.1007/978-981-15-0458-7_26, (359-372), . Watanabe T, Ichijo M and Kamata T (2019) Uneventful Pregnancy and Delivery after Thrombolysis Plus Thrombectomy for Acute Ischemic Stroke: Case Study and Literature Review, Journal of Stroke and Cerebrovascular Diseases, 10.1016/j.jstrokecerebrovasdis.2018.09.002, 28:1, (70-75), Online publication date: 1-Jan-2019. Singhal V and Wanchoo J (2019) Intravenous Thrombolysis Textbook of Neuroanesthesia and Neurocritical Care, 10.1007/978-981-13-3387-3_25, (359-370), . Kozberg M and Camargo E (2019) Management of Maternal Stroke and Mitigating Risk, Current Treatment Options in Cardiovascular Medicine, 10.1007/s11936-019-0770-z, 21:11, Online publication date: 1-Nov-2019. Ryman K, Pace W, Smith S and Fontaine G (2019) Alteplase Therapy for Acute Ischemic Stroke in Pregnancy: Two Case Reports and a Systematic Review of the Literature, Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 10.1002/phar.2278, 39:7, (767-774), Online publication date: 1-Jul-2019. Jiang Z and Hu Z (2018) Remote Intracerebral Hemorrhage Following Intravenous Thrombolysis in Pregnancy at 31 Weeks Gestation, The Neurologist, 10.1097/NRL.0000000000000165, 23:1, (19-22), Online publication date: 1-Jan-2018. Stokes N and Kikucki J (2018) Management of Cardiac Arrest in the Pregnant Patient, Current Treatment Options in Cardiovascular Medicine, 10.1007/s11936-018-0652-9, 20:7, Online publication date: 1-Jul-2018. Reining-Festa A, Földy D, Coulibaly-Wimmer M, Eischer L, Heger M and Fertl E (2016) Intravenous thrombolysis of stroke in early pregnancy: a case report and review of the literature, Journal of Neurology, 10.1007/s00415-016-8369-8, 264:2, (397-400), Online publication date: 1-Feb-2017. Majersik J (2017) Inherited and Uncommon Causes of Stroke, CONTINUUM: Lifelong Learning in Neurology, 10.1212/CON.0000000000000432, 23:1, (211-237), Online publication date: 1-Feb-2017. Sah R and Kausar S (2017) Medical problems in pregnancy, Clinical Medicine, 10.7861/clinmedicine.17-6-588b, 17:6, (588.3-589), Online publication date: 1-Dec-2017. Boyko M, Iancu D, Lesiuk H, Dowlatshahi D and Shamy M (2015) Decision Making and the Limits of Evidence, The Neurohospitalist, 10.1177/1941874415594120, 6:2, (70-75), Online publication date: 1-Apr-2016. Leffert L, Clancy C, Bateman B, Cox M, Schulte P, Smith E, Fonarow G, Kuklina E, George M and Schwamm L (2016) Treatment patterns and short-term outcomes in ischemic stroke in pregnancy or postpartum period, American Journal of Obstetrics and Gynecology, 10.1016/j.ajog.2015.12.016, 214:6, (723.e1-723.e11), Online publication date: 1-Jun-2016. Meves S and Hellwig K (2016) Zerebrovaskuläre Erkrankungen in der Schwangerschaft, gynäkologie + geburtshilfe, 10.1007/s15013-016-0850-z, 21:S1, (24-32), Online publication date: 1-Sep-2016. Meves S and Hellwig K (2016) Zerebrovaskuläre Erkrankungen in der Schwangerschaft, NeuroTransmitter, 10.1007/s15016-016-5396-8, 27:4, (32-41), Online publication date: 1-Apr-2016. Kate M, Parthasarathy R and Shuaib A (2016) Intravenous Thrombolysis and Anti-thrombotics Ischemic Stroke Therapeutics, 10.1007/978-3-319-17750-2_3, (13-25), . Leffert L, Clancy C, Bateman B, Bryant A and Kuklina E (2015) Hypertensive Disorders and Pregnancy-Related Stroke, Obstetrics & Gynecology, 10.1097/AOG.0000000000000590, 125:1, (124-131), Online publication date: 1-Jan-2015. Masingue M and Alamowitch S (2015) Nouvelles limites de la thrombolyse intraveineuse dans le traitement des infarctus cérébraux, La Presse Médicale, 10.1016/j.lpm.2014.07.027, 44:5, (515-525), Online publication date: 1-May-2015. Moatti Z, Gupta M, Yadava R and Thamban S (2014) A review of stroke and pregnancy: incidence, management and prevention, European Journal of Obstetrics & Gynecology and Reproductive Biology, 10.1016/j.ejogrb.2014.07.024, 181, (20-27), Online publication date: 1-Oct-2014. HIRANO T (2013) Acute Revascularization Therapy in Pregnant Patients, Neurologia medico-chirurgica, 10.2176/nmc.53.531, 53:8, (531-536), . Al-Mufti F, Schirmer C, Starke R, Chaudhary N, De Leacy R, Tjoumakaris S, Haranhalli N, Abecassis I, Amuluru K, Bulsara K and Hetts S (2021) Thrombectomy in special populations: report of the Society of NeuroInterventional Surgery Standards and Guidelines Committee, Journal of NeuroInterventional Surgery, 10.1136/neurintsurg-2021-017888, (neurintsurg-2021-017888) Steinberg A and Moreira T (2016) Neuroendocrinal, Neurodevelopmental, and Embryotoxic Effects of Recombinant Tissue Plasminogen Activator Treatment for Pregnant Women with Acute Ischemic Stroke, Frontiers in Neuroscience, 10.3389/fnins.2016.00051, 10 March 2013Vol 44, Issue 3 Advertisement Article InformationMetrics © 2013 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.111.000134PMID: 23391770 Manuscript receivedNovember 12, 2012Manuscript acceptedJanuary 3, 2013Originally publishedFebruary 7, 2013 Keywordsmiddle cerebral artery occlusionpregnancythrombolysisendovascular treatmentMRIPDF download Advertisement SubjectsComputerized Tomography (CT)Ischemic StrokeTreatment
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