{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T10:10:05Z","timestamp":1789726205466,"version":"4.0.1"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:p>Angioedema without concomitant urticaria is a well-known complication of treatment with the recombinant tissue-type plasminogen activator (r-tPA) alteplase and its genetically modified variant tenecteplase. It is potentially lethal when causing airway obstruction and can require intubation. The latest guideline for the early management of patients with acute ischemic stroke from the American Heart Association\/American Stroke Association advises to treat this complication initially by interfering with the histamine pathway. This article aims to clarify the pathophysiological mechanism of r-tPA-induced angioedema and provides several arguments that this condition is primarily bradykinin-mediated and hence should be treated initially by intervening with the bradykinin pathway. Second, other\u2014less frequently reported\u2014adverse symptoms after r-tPA therapy and their proposed pathophysiological mechanisms leading to specific treatment are described. This manuscript describes the need for an update of the section \u201c3.5 IV alteplase\u201d from the American Heart Association\/American Stroke Association guideline to treat this r-tPA-induced angioedema adequately and prevent potentially fatal outcomes.<\/jats:p>","DOI":"10.1161\/strokeaha.124.047060","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T09:00:43Z","timestamp":1719565243000},"page":"2193-2197","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Angioedema After Use of Recombinant Tissue-Type Plasminogen Activators in Stroke"],"prefix":"10.1161","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6650-2199","authenticated-orcid":true,"given":"Evelien M.","family":"Hutten","sequence":"first","affiliation":[{"name":"Department of Allergology (E.M.H., A.A.J.M.v.d.V., R.G.P.), University Medical Center Groningen, University of Groningen, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7032-9571","authenticated-orcid":true,"given":"Annick A.J.M.","family":"van de Ven","sequence":"additional","affiliation":[{"name":"Department of Allergology (E.M.H., A.A.J.M.v.d.V., R.G.P.), University Medical Center Groningen, University of Groningen, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1270-5684","authenticated-orcid":true,"given":"Rik","family":"Mencke","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology, Division of Pathology (R.M.), University Medical Center Groningen, University of Groningen, Netherlands."},{"name":"Department of Neurosurgery, Carl von Ossietzky University Oldenburg, Germany (R.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4856-019X","authenticated-orcid":true,"given":"Rick G.","family":"Pleijhuis","sequence":"additional","affiliation":[{"name":"Department of Allergology (E.M.H., A.A.J.M.v.d.V., R.G.P.), University Medical Center Groningen, University of Groningen, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01054-6"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.122.042335"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000058840.66596.1a"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.116.013334"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.122.042335"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0000000000000211"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00634-8"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2017.09.039"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajem.2018.03.018"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.122.040052"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2016-216133"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinane.2014.06.013"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/postgradmedj-2016-134501"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.2869"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12472"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1179\/1743132813Y.0000000302"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S0022-3565(24)39065-2","article-title":"Metabolism of bradykinin In vivo in humans: identification of BK1-5 as a stable plasma peptide metabolite.","volume":"294","author":"Murphey LJ","year":"2000","unstructured":"Murphey, LJ, Hachey, DL, Oates, JA, Morrow, JD, Brown, NJ. 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