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.

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.

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.

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.