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Targeting the Bradykinin Pathway: Tranexamic Acid for Angiotensin-Converting Enzyme Inhibitor–Induced Angioedema By Cecilia Schowe, PharmD, MS, and Nikki Batterman, PharmD
SAEM PULSE | MARCH-APRIL 2026
Background
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Angioedema presents to the emergency department (ED) with varying degrees of severity and accounts for an estimated 80,000 to 112,000 ED visits annually, with possible overlap with anaphylaxis. Angioedema is characterized by transient subcutaneous or submucosal swelling that may occur alone or in conjunction with anaphylaxis. It most commonly involves the face, neck, or throat and may be accompanied by urticaria or respiratory distress.
Pathophysiology of Angioedema Angioedema occurs via two primary pathophysiologic pathways: histamine mediated and bradykinin mediated. Histamine-mediated
angioedema is most commonly triggered by medications, food, or animal exposure and is characterized by rapid onset, symmetric swelling (often affecting the lips and periorbital area), and associated urticaria, flushing, or pruritus. Bradykinin-mediated angioedema is most commonly associated with angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers, or hereditary angioedema. Compared with histamine-mediated angioedema, symptom onset is slower and more gradual, typically occurring over several hours. Swelling is more focal and often asymmetric, primarily involving the tongue and lips. Additionally, bradykinin-mediated
angioedema lacks associated urticaria and pruritus. The precise mechanism underlying ACE-I–induced angioedema is not fully understood; however, it is thought to result from the accumulation of bradykinin. Angiotensin-converting enzyme is responsible for bradykinin degradation, and its inhibition leads to increased bradykinin levels. This increase subsequently promotes activation of plasmin, factor XII, and kallikrein, creating a positive feedback loop that further amplifies bradykinin production and ultimately results in tissue edema. The overall incidence of ACEI-induced angioedema is around 0.1% to 0.7%, with up to 40% of all