Orolingual Angioedema After Tissue Plasminogen Activator Administration in Patients Taking Angiotensin-Converting Enzyme Inhibitors

Abstract

Orolingual angioedema is a rare adverse effect (1%–5%) of tissue plasminogen activator (tPA) that can lead to significant morbidity in patients with acute ischemic stroke. It is thought that increased levels of bradykinin and histamine resulting from tPA administration can result in angioedema. Angiotensin-converting enzyme (ACE) inhibitors can also lead to increased levels of bradykinin and appear to be a risk factor for tPA-associated angioedema. A literature review was conducted to examine previous cases of orolingual angioedema associated with tPA administration in patients also taking ACE inhibitors to better understand the relationship between ACE inhibitors and tPA-induced angioedema. Over a 20-year period, 27 patients who experienced angioedema with tPA while on ACE inhibitor therapy were identified. In this patient population, the onset of angioedema symptoms appeared as soon as 15 min after the tPA bolus and as late as 2 hr after the tPA infusion. Most patients required a combination of supportive medications such as corticosteroids (81.5%), antihistamines (74%), and epinephrine (18.5%) for the management of angioedema. Severe presentations of orolingual angioedema resulted in intubation for airway protection (26%). Symptom resolution ranged from shortly after the administration of supportive medications to 72 hr after symptom onset. Orolingual angioedema after tPA administration has the potential to cause significant morbidity, indicating patients should be monitored closely for a few hours after administration for the development of airway compromise. ACE inhibitors should not be the preferred antihypertensive agents for patients who require blood pressure lowering prior to tPA administration.

Alteplase associated Orolingual angioedema: A case report and literature review

“…ACE inhibitors are the most recognized predisposing factors for OA. [ 7 ] One hypothesis is a bradykinin-mediated pathway in which RT-PA hydrolyzes plasminogen to plasmin, which in turn activates the kinin pathway and increases bradykinin production. [ 8 ] Bradykinin is a potent pro-inflammatory and pro-edematous peptide that increases vascular permeability and vasodilatation, leading to angioedema.…”

Angioedema Secondary to tPA Use in Acute Ischemic Stroke Patient with Hypertension: A Case Report

“…Angioedema after tPA infusion is a known complication and has an incidence of approximately 1-5%. 7 Additionally, it is suggested that angioedema will typically occur on the contralateral side of the ischemic hemisphere. 6 Several studies have proposed certain predisposing factors to the development of angioedema with the administration of tPA.…”