UMEM Educational Pearls

Category: Critical Care

Title: Thrombolytic-induced Angioedema:

Keywords: angioedema, stroke, CVA, t-PA, alteplase, thrombolysis (PubMed Search)

Posted: 12/20/2022 by Zach Rogers, MD
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Thrombolytic-induced angioedema is a known complication of alteplase or tenecteplase administration, occurring in 0.9-5.1% of patients who received thrombolytics due to ischemic stroke. Angioedema occurs due to activation of the kinin and complement pathway by plasminogen, leading to both bradykinin and histamine release.

Swelling most commonly occurs acutely while the t-PA is infusing, but can have a delayed presentation up to 24 hours post administration. It normally has an orolingual distribution, although in severe cases there can be laryngeal involvement as well. There is a 4-fold-increase occurrence in patients who take ACE inhibitor medications [1] with some studies noting a high prevalence in strokes involving the right insular brain region [2].

Once identified, the t-PA infusion should be immediately discontinued. As there may be histamine involvement in angioedema formation, patients are initially treated with steroids, H1, and H2 blockers with as needed epinephrine injections.

Given the orolingual predominance, airway obstruction must be ruled out and the patient closely monitored with emergent intubation performed if necessary.

As the kinin pathway (bradykinin) appears to play the largest role in angioedema formation, C1 esterase inhibitors and bradykinin inhibitors can be used in severe or refractory cases [3,4].

However, most cases are mild and resolve with t-PA discontinuation and the initial steroid and histamine blockade.



1.            Lin SY, Tang SC, Tsai LK, Yeh SJ, Hsiao YJ, Chen YW, et al. Orolingual angioedema after alteplase therapy of acute ischaemic stroke: incidence and risk of prior angiotensin-converting enzyme inhibitor use.Eur J Neurol. 2014; 21:1285–1291. doi: 10.1111/ene.12472

2.            Fröhlich K, Macha K, Gerner ST, Bobinger T, Schmidt M, Dörfler A, Hilz MJ, Schwab S, Seifert F, Kallmünzer B, Winder K. Angioedema in Stroke Patients With Thrombolysis. Stroke. 2019 Jul;50(7):1682-1687. doi: 10.1161/STROKEAHA.119.025260. Epub 2019 Jun 11. PMID: 31182002.

3.            Pahs L, Droege C, Kneale H, Pancioli A. A Novel Approach to the Treatment of Orolingual Angioedema After Tissue Plasminogen Activator Administration. Ann Emerg Med. 2016 Sep;68(3):345-8. doi: 10.1016/j.annemergmed.2016.02.019. Epub 2016 May 10. PMID: 27174372.

4.            Brown E, Campana C, Zimmerman J, Brooks S. Icatibant for the treatment of orolingual angioedema following the administration of tissue plasminogen activator. Am J Emerg Med. 2018; 36:1125.e1–1125.e2. doi: 10.1016/j.ajem.2018.03.018