ISSN: 1524-4628 Copyright © 2006 American Heart Association. All rights reserved. Print ISSN: 0039-2499. OnlineStroke is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX 72514

DOI: 10.1161/01.STR.0000230286.95513.c2 published online Jun 22, 2006; Stroke

Kathleen M. Wiese, Arun Talkad, Maureen Mathews and David Wang With Cardioembolic Stroke

Intravenous Recombinant Tissue Plasminogen Activator in a Pregnant Woman

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Intravenous Recombinant Tissue Plasminogen Activator in aPregnant Woman With Cardioembolic Stroke

Kathleen M. Wiese, DO; Arun Talkad, MD; Maureen Mathews, APN; David Wang, DO

Background and Purpose—Historically, the use of tissue plasminogen activator (tPA) thrombolysis in pregnancy has beenregarded as relatively contraindicated. Underlying this stance has been the concern over the risk of bleeding complications inboth mother and child.

Summary of Case—We report the successful use of intravenous recombinant tPA (rtPA) thrombolysis in a pregnantwoman with acute cardioembolic stroke.

Conclusions—The patient improved clinically, did not develop complications after receiving rtPA, and at 37 weeks’gestation, delivered a healthy infant, demonstrating that rtPA thrombolysis may be used safely in pregnant women.(Stroke. 2006;37:000-000.)

Key Words: thrombolysis � tissue plasminogen activator

Although not addressed specifically in the latest guidelinesfor tissue plasminogen activator (tPA) thrombolysis in

acute ischemic stroke,1 the use of tPA in pregnant patientshistorically has been regarded as relatively contraindicated.The fundamental risks underlying opposition to thrombolytictherapy in pregnancy include placental abruption, retropla-cental hemorrhage, abortion, peripartum uterine bleeding, andpostpartum hemorrhage. For these reasons, no large con-trolled trials of thrombolytic agents in pregnant patients havebeen undertaken. To date, only case reports and case serieshave been published, citing myriad indications for thrombolysisand thrombolytic agents. Of these reports, there have been 3citing the use of thrombolytics specifically in the setting of acutearterial ischemic stroke.2–4 Two cases reported thrombolytic usein women with first-trimester pregnancies, noted improve-ment in the patients’ stroke symptoms after intervention, andreported the birth of healthy infants at term. However, bothcases were complicated by the development of intracerebralhemorrhages after lysis. A third case reported the successfuluse of intra-arterial recombinant tPA (rtPA) in a womanpregnant for 37 weeks, demonstrating that rtPA may be usedthroughout pregnancy. In this case, a healthy infant wasdelivered only 3 days after treatment.4

Herein we report the successful use of intravenous rtPAthrombolysis, uncomplicated by hemorrhage development, ina woman who was 13 weeks pregnant with acute cardioem-bolic ischemic stroke secondary to presumed prosthetic mitralvalve thrombosis.

Case ReportThe patient was a 33-year-old, right-handed white womanwho presented to an outlying community hospital �25 to 30

minutes after developing acute onset of right-sided hemipa-resis and expressive aphasia. At that facility, she was found tohave normal vital signs, and laboratory studies revealed normalperipheral cell counts, electrolytes, and coagulation values. Anoncontrast head computed tomography scan was remarkableonly for a hyperdense left middle cerebral artery sign.

Recording of the patient’s medical history revealed that 3years previously, she had undergone mitral valve replacementsurgery for a history of mitral valve prolapse. Subsequentlythe patient had been placed on long-term Coumadin therapy,which was later switched to subcutaneous heparin when shewas found to be pregnant. At presentation, the patient was G5P3

and 13 weeks’ pregnant. She was noted to have delivered ahealthy baby only 6 months before via induced vaginal deliveryafter a pregnancy then complicated by gestational diabetesmellitus.

After obtaining informed consent from the patient’s do-mestic partner, intravenous rtPA was administered per stan-dard protocol (0.9 mg/kg over 60 minutes as a 10% bolus and90% infusion). Subsequently the patient was transferred viaLifeFlight to the OSF Stroke Center for potential receipt ofintra-arterial tPA and for tertiary-level neurological care. Onher arrival, the patient was found to have a right-sided hemipa-resis and fluctuating expressive aphasia with a maximum Na-tional Institutes of Health Stroke Scale (NIHSS) score of 13.Because 6 hours had elapsed since the onset of symptoms, thedecision was made to forego intra-arterial thrombolysis.

The following morning, a noncontrast computed tomogra-phy scan revealed hypodensities in the left caudate, putamen,globus pallidus, anterior limb of the internal capsule, andadjacent white matter, with effacement of the left frontal

Received March 10, 2006; final revision received May 10, 2006; accepted May 23, 2006.From the Department of Neurology (K.M.W., A.T.), University of Illinois at Peoria; and the OSF Stroke Center and Network (M.M., D.W.), Illinois

Neurological Institute, OSF St. Francis Medical Center, Peoria, Ill.Correspondence to Kathleen M. Wiese, DO, University of Illinois at Peoria, OSF St. Francis Medical Center, Department of Neurology, 530 NE Glen

Oak Ave, Peoria, IL 61637. E-mail kathleenwiese@yahoo.com© 2006 American Heart Association, Inc.

Stroke is available at http://www.strokeaha.org DOI: 10.1161/01.STR.0000230286.95513.c2

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horn. No evidence of hemorrhage was seen. Carotid Dopplerfindings were normal, and a transthoracic echocardiogramwas remarkable only for a mechanical mitral valve prosthesisand moderate tricuspid regurgitation.

Clinically, the patient improved to an NIHSS of 11 and wasplaced on prophylactic therapeutic enoxaparin 80 mg subcu-taneously twice daily. She was then transferred to an outlyingrehabilitation facility, restarted on warfarin therapy, andultimately improved to an NIHSS of 4. Six months after herstroke and after an uncomplicated pregnancy, the patientdelivered a 37-week, healthy male infant via repeat cesareansection.

DiscussionAlthough pregnancy has historically been widely regarded asa relative contraindication to thrombolytic therapy, �200pregnant patients have been reported to have received suchtherapy and overall with low maternal mortality (1%), lowfetal loss (6%), and a low incidence of preterm delivery(6%).5 Furthermore, in a series of 172 pregnant patients whohad received thrombolytics, infants were reported to be normalon their initial examinations.6

To date, most reported cases have involved the use ofstreptokinase for thrombolysis, with fewer using urokinase.Fewer cases yet have involved the use of rtPA and othernewer, more fibrin-specific and less antigenic thrombolyticagents. Even so, the safety data in favor of these agents arefairly compelling and have led other authors to view the useof tPA in pregnancy as at least tenable and likely safe.2–4 Onthe basis of this case, we affirm such may be the case andspeculate that the use of relatively newer agents, like rtPA,may add an additional margin of safety by virtue of their fibrinspecificity and, at least versus streptokinase, less antigenicprofile.

As Ahearn et al reported,5 at least as of 2002, there were 6published reports of pregnant women who had received rtPAfor various indications, including thrombosed prostheticvalves, myocardial infarction, and pulmonary embolism.None of these cases was associated with adverse maternaloutcomes, and although a single case of fetal death wasreported, it was unrelated to the use of rtPA. Additionally,

Elford et al3 reported on the use of intra-arterial rtPA in a rightmiddle cerebral artery distribution thromboembolic stroke re-lated to ovarian hyperstimulation syndrome. Although the pa-tient developed a hematoma after lysis, she did graduallyimprove neurologically and delivered a healthy, term infant.

Therefore, based on the evidence to date, the use of thrombo-lytics may be feasible in pregnant patients. Given that a signif-icant proportion of all maternal deaths are attributable to ische-mic arterial stroke and furthermore, that an estimated 42% to63% of pregnancy-associated stroke survivors have residualneurological deficits thereafter,7 the benefits of rtPA thrombo-lysis may outweigh the risks when given to pregnant womenwhen indicated, even as early as the first trimester and as late asthe late third trimester.4 Further exploration of the benefits ofrtPA thrombolysis in this setting is warranted.

DisclosuresD.W. reports prior receipt of modest research grant funds from ESPPharma. These funds were not used in generating this article. Theauthor reports receipt of significant speakers’ bureau funds/honorariafrom Bristol-Meyers-Squibb, Sanofi, Pfizer, and Boehringer-Ingelheim pharmaceuticals. Monies obtained in such service havenot been applied to generation of this article. The other authors haveno conflicts of interest to report.

References1. Adams HP, Brott TG, Furlan AJ, Gomez CR, Grotta J, Helgason CM,

Kwiatkowski T, Lyden PD, Marler JR, Torner J, Feinberg W, Mayberg M,Thies W. Guidelines for thrombolysis therapy for acute stroke: a sup-plement to the guidelines for the management of patients with acuteischemic stroke. Circulation. 1996;94:1167–1174.

2. Dapprich M, Boessenecker W. Fibrinolysis with alteplase in a pregnantwoman with stroke. Cerebrovasc Dis. 2002;13:290.

3. Elford K, Leader A, Wee R, Stys PK. Stroke in ovarian hyperstimulationsyndrome in early pregnancy treated with intra-arterial rt-PA. Neurology.2002;59:1270–1272.

4. Johnson D, Kramer D, Cohen E, Rochon M, Rosner M, Weinberger J.Thrombolytic therapy for acute stroke in late pregnancy with intra-arterialrecombinant tissue plasminogen activator. Stroke. 2005;36:e53–e55.

5. Ahearn GS, Hadjiliadis D, Govert JA, Tapson VF. Massive pulmonaryembolism during pregnancy successfully treated with recombinant tissueplasminogen activator. Arch Intern Med. 2002;162:1221–1227.

6. Turrentine MA, Braems G, Ramirez MM. Use of thrombolytics for thetreatment of thromboembolic disease during pregnancy. Obstet GynecolSurv. 1995;50:534–541.

7. Turan TN, Stern BJ. Stroke in pregnancy. Neurol Clin. 2004;22:821–840.

2 Stroke August 2006

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