Angioedema reported with tissue plasminogen activators: A need to communicate on bradykinin- and histamine-mediated mechanisms - 25/02/26

Doi : 10.1016/j.therap.2025.12.004

Anaïs Maurier ^a,⁎ , Frédérique Beau-Salinas ^a, Bérenger Largeau ^a, Sophie Gautier ^b, Elisabeth Polard ^c, Annie-Pierre Jonville-Bera ^a

^a Department of Pharmacosurveillance, Pharmacovigilance Regional Center of Centre Val-de-Loire, University Hospital of Tours, 37000 Tours, France

^b Pharmacology Department, Regional Centre of Pharmacovigilance of Nord Pas de Calais, University Hospital of Lille, 59000 Lille, France

^c Pharmacovigilance, Pharmacoepidemiology and Drug Information Center - Department of Clinical Pharmacology, University Hospital of Rennes, 35000 Rennes, France

^⁎ Corresponding author. Regional University Hospital Centre Tours, Department of Pharmacosurveillance, Pharmacovigilance Regional Center of Centre Val-de-Loire, 2, boulevard Tonnellé, 37044 Tours cedex, France. Regional University Hospital Centre Tours, Department of Pharmacosurveillance, Pharmacovigilance Regional Center of Centre Val-de-Loire 2, boulevard Tonnellé Tours cedex 37044 France

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Wednesday 25 February 2026

Abstract

Aim of the study

Angioedema (AE) is a potentially life-threatening adverse effect. The mechanism can be either bradykinin- (BK-AE) or histamine-mediated (Hi-AE), each requiring different management. AE are reported with recombinant tissue plasminogen activators (alteplase and tenecteplase), for which an immunoallergic or bradykinic mechanism is suggested. The aim of this study was to describe the characteristics of cases of AE (BK or Hi) reported with rt-PA to the French Regional Pharmacovigilance Centers in order to optimize their identification and management.

Methods

All cases of AE reported with alteplase or tenecteplase until 30 November, 2023 were analyzed and classified as Hi-AE or BK-AE using the clinical manifestations, the management and the allergological workup.

Results

We analyzed 151 cases of AE, with a median time to onset of 1 h (IQR = 1–2 h), all localized at the head. From them, 150 were with alteplase use for acute ischemic stroke (98%) or myocardial infarction (2%), and 1 with tenecteplase. Of them 107 (71%) could be clearly categorized and were classified as 98 (92%) cases of BK-AE and 9 (8%) cases of Hi-AE. When the use of icatibant or C1 esterase inhibitor is specified, it was the 1st-line treatment for 32/47 (68%) patients.

Conclusion

The majority of cases of AE reported with rt-PA, are BK-AE involving alteplase. This is consistent with the effects of rt-PA, which activates the kinin pathway by hydrolyzing plasminogen to plasmin, resulting in the formation of bradykinin. Clinicians need to be informed of this mechanism, in order to early prescribe the appropriate treatment, as we detect that it was not systematically used as 1st-line therapy for a lot of cases.

Le texte complet de cet article est disponible en PDF.

Keywords : Angioedema, Tissu plasminogen activator, Alteplase, Adverse effects