Asymmetric Angioneurotic Edema Associated With Thrombolysis for Acute Stroke

doi:10.1016/S0196-0644(97)70147-1

Annals of Emergency Medicine

Volume 30, Issue 2, August 1997, Pages 227-229

https://doi.org/10.1016/S0196-0644(97)70147-1 Get rights and content

Abstract

We present a case of acute asymmetric angioneurotic edema associated with the use of recombinant tissue plasminogen activator (rtPA) for acute ischemic stroke. rtPA was administered for an acute ischemic stroke in accordance with the recently reported National Institute of Neurological Disorders and Stroke protocol, after which marked asymmetric angioedema requiring upper-airway control developed. Although atypical and anaphylactoid reactions have been reported with the use of rtPA for acute myocardial infarction, to our knowledge this is the first case report of asymmetric angioedema associated with the use of rtPA for acute ischemic stroke. [Pancioli A, Brott T, Donaldson V, Miller R: Asymmetric angioneurotic edema associated with thrombolysis for acute stroke. Ann Emerg Med August 1997;30:227-229.]

Section snippets

INTRODUCTION

The use of recombinant tissue plasminogen activator (rtPA) for acute stroke has generated considerable interest since the publication of the first positive results from a large trial and the subsequent approval of rtPA by the US Food and Drug Administration.¹ One rare side effect of tPA is angioneurotic edema. We report a case of acute asymmetric angioneurotic edema associated with the use of rtPA for acute stroke.

CASE REPORT

A 51-year-old woman presented with acute-onset left hemiparesis. Her medical history was remarkable for hypertension, for which she was taking enalapril maleate; and for schizophrenia, for which she was taking thiothixene hydrochloride and benztropine mesylate. The patient had no history of angioneurotic edema, cerebrovascular disease, seizure disorder, or diabetes; no family history of hereditary angioneurotic edema; and no known allergies.

On initial examination the patient was slightly

DISCUSSION

Angioneurotic edema is a potentially life-threatening problem that is commonly associated with the use of ACE inhibitors and has been reported with the use of thrombolytic agents.3, 4, 5, 6, 7, 8, 9 Plasmin, a serine protease with fibrinolytic properties, also acts on many other substrates, including the first component of complement, C1.10, 11 Plasmin can convert C1 to its active form, which then activates C4, C2 and the rest of the complement cascade, potentially triggering angioneurotic

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A Novel Approach to the Treatment of Orolingual Angioedema After Tissue Plasminogen Activator Administration
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Orolingual angioedema is a rare adverse effect of tissue plasminogen activator (tPA), with an incidence of 1% to 5%. There are currently no published reports describing resolution of tPA-induced orolingual angioedema with complement inhibitor therapy. A 72-year-old man receiving home angiotensin-converting enzyme inhibitor therapy presented to the emergency department with newly developed orolingual angioedema after treatment with tPA for acute ischemic stroke. Therapy was initiated with intravenous methylprednisolone 125 mg, famotidine 20 mg, and diphenhydramine 50 mg, without significant improvement. Because of increased concern for airway protection, plasma-derived C1 esterase inhibitor was administered. Concerns about progressive and airway-threatening orolingual angioedema subsided 2 hours after administration, and invasive airway maneuvers were avoided. Orolingual angioedema is an infrequent, severe adverse effect of tPA for treatment of acute ischemic stroke. Complement inhibitors may be an additional therapeutic option for patients presenting with orolingual angioedema with potential airway compromise that is refractory to standard anaphylactic therapies.
Persistent, severe post-thrombolysis angioedema: Simple management of a difficult problem
2015, American Journal of Otolaryngology - Head and Neck Medicine and Surgery
Citation Excerpt :
Bradykinin increases vascular permeability producing angioedema. A secondary action of t-PA is in initiation of the complement cascade [9]. The subsequent activation of C3 and C5 leads to mast cell degranulation and histamine release, further propagating the angioedema.
Post-thrombolysis orolingual angioedema in the setting of managing acute stroke is reported in the literature as most often being mild and self-limiting. We present a case of severe angioedema resulting in persistent macroglossia, representing a different end of the spectrum of disease than that referenced in the literature. Despite the severity of the tongue edema in our case, it did resolve with a relatively simple intervention. In addition to highlighting that post-thrombolysis angioedema can be potentially life threatening, this report reviews the pathophysiology of this condition and discusses management options for macroglossia in this setting.
Readministration of intravenous alteplase in acute ischemic stroke patients: Case series and systematic review
2015, American Journal of Emergency Medicine
Massive macroglossia secondary to angioedema: A review and presentation of a case
2015, Journal of Oral and Maxillofacial Surgery
Macroglossia is a rare condition, but can severely affect the oral and maxillofacial region. Angioedema is a condition resulting from multiple mechanisms, all of which can result in macroglossia. This report describes an unusual case of acquired macroglossia in an adult resulting from chronic edema secondary to angioedema in the setting of stroke. The patient had a morbidly enlarged tongue and presented with clinical signs and symptoms consistent with massive macroglossia. She required surgical intervention for acute management of her symptoms and definitive treatment of her macroglossia.
Orolingual angiodema associated with alteplase treatment of acute stroke: A reappraisal
2015, Journal of Stroke and Cerebrovascular Diseases
Citation Excerpt :
Bradykinin is metabolized mainly by 3 metallopeptidases: angiotensin converting enzyme, aminopeptidase P, and kininase I. In patients who take an ACEi and receive rt-PA, the combination of increased release of bradykinin mediated by alteplase and decreased breakdown of bradykinin due to ACEi may enhance the risk of angioedema.5,35 In a study, the risk of angioedema in stroke patients treated with rt-PA was strongly associated with ACEi use, with a relative risk of 13.6.3
Orolingual angioedema has been increasingly recognized as a potentially life-threatening complication associated with alteplase treatment of stroke. Concomitant treatment with an angiotension converting enzyme inhibitor (ACEi) and localization of infarction in the territory of middle cerebral artery seem to be associated with a higher risk of this complication.
We report the cases of orolingual angioedema among the patients undergoing alteplase treatment in our Stroke Unit. Additionally, we reviewed the literature to evaluate the pathophysiology, clinical characteristics, and treatment options.
In our Stroke Unit, among 236 patients given alteplase for acute stroke, 8 patients (3.4%) developed angioedema. The clinical picture varied from localized labial edema to extensive lingual edema with respiratory distress but in all cases it gradually resolved with symptomatic treatment. Seven patients had a hemispheric stroke (4 with lateralized angioedema, contralateral to the ischemic lesion), whereas the other 1 patient had a right superior cerebellar artery stroke (with lateralized angioedema, ipsilateral to the ischemic lesion). The National Institutes of Health Stroke Scale score at admission ranged from 6 to 24 (median 12.5). Five patients were taking an ACEi. Our results are similar to previously published data. In the literature, it appears that orolingual angioedema occurs in .2-5.1% of all stroke patients receiving Alteplase treatment.
Orolingual angioedema is a potential complication of which treating physicians in stroke units need to be aware, even in those cases without history of ACEi treatment and without infarction in the territory of the middle cerebral artery. All patients who receive alteplase treatment should be monitored carefully.
Orolingual angioedema associated with olmesartan use after recombinant tissue plasminogen activator treatment of acute stroke
2014, Annals of Allergy, Asthma and Immunology

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^☆: From the Departments of Emergency Medicine,^* Neurology,^‡ Pediatrics,^§ and Medicine,^∥ University of Cincinnati College of Medicine, Cincinnati, OH.

^☆☆: Address for reprints: Arthur Pancioli, MD, Department of Emergency Medicine, University of Cincinnati, PO Box 670769, Cincinnati, OH 45267-0769, 513-558-5281, Fax 513-558-5791, E-mail [email protected]

^★: Reprint no. 47/1/82184

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Asymmetric Angioneurotic Edema Associated With Thrombolysis for Acute Stroke☆,☆☆,★

Abstract

Section snippets

INTRODUCTION

CASE REPORT

DISCUSSION

Lancet

Tissue plasminogen activator for acute ischemic stroke

N Engl J Med

Measurements of acute cerebral infarction: A clinical Examination scale

Stroke

Drug-induced, life-threatening angioedema revisited

Laryngoscope

Case report: Angioedema during therapy with recombinant tissue plasminogen activator

Br J Haematol

Anaphylactoid reaction during an infusion of recombinant tissue-type plasminogen activator for acute myocardial infarction

Can J Cardiol