ALTEPLASE-ASSOCIATED ANGIOEDEMA: NEW TREATMENT OPTIONS

Abstract

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Alteplase (recombinant tissue plasminogen activator or tPA) has revolutionized the management of acute ischemic stroke since its FDA approval in 1995. Intracerebral bleed is the most known and feared complication after tPA administration. tPA-associated orolingual angioedema (TAOA) is a less common but potentially fatal complication of tPA. We report a patient who developed hemi-orolingual angioedema after receiving tPA. CASE PRESENTATION: A 79-year-old female presented with sudden onset right-sided weakness with initial National Institutes of Health Stroke Scale score of 4. CT head was negative for intracranial bleed and a CT angiogram with perfusion of the head showed occlusion of P2 segment of the left posterior cerebral artery. She received tPA bolus followed by infusion and was transferred to the intensive care unit. She developed right hemi-orolingual angioedema without evidence of airway compromise one and half hours after tPA initiation. Administration of intravenous corticosteroids and antihistamines failed to improve angioedema. She was subsequently treated with 2 units of fresh frozen plasma (FFP) with complete resolution of swelling within 2 hours. DISCUSSION: Alteplase cleaves plasminogen to plasmin which degrades thrombus-bound fibrin. Plasmin also activates the kinin and complement pathways causing increased bradykinin and histamine release respectively. Bradykinin-mediated vasodilation appears to be the primary cause of TAOA. TAOA has an incidence of 0.2-5.1%. It usually develops hemi-lingually and tends to be contralateral to the ischemic side possibly due to autonomic dysfunction from insular cortex ischemia. However, this may not always be true since our patient had contralateral angioedema without insular cortex involvement. Initial management includes corticosteroids and antihistamines which are less effective for bradykinin-mediated angioedema. FFP contains kininase 2 which degrades bradykinin and hence is effectively used off label for angiotensin-converting enzyme inhibitor-induced angioedema. As TAOA also follows the bradykinin pathway, we treated our patient with FFP. To our knowledge, this is the first-ever case of TAOA treated with FFP. Other potential treatment options include C1 esterase inhibitor, icatibant (bradykinin receptor antagonist), and ecallantide (kallikrein inhibitor) which are being used for hereditary angioedema and need to be studied for TAOA. CONCLUSIONS: TAOA is a life-threatening complication that typically occurs in the first 4 hours after tPA administration. Physicians should be aware of this uncommon side effect for early recognition and treatment. Treatment targeting the bradykinin pathway like FFP might be more effective and needs further investigation. REFERENCE #1: Rathbun KM. Angioedema after thrombolysis with tissue plasminogen activator: an airway emergency. Oxf Med Case Reports. 2019;2019(1):omy112. Published 2019 Jan 24. doi:10.1093/omcr/omy11 REFERENCE #2: Hemi-orolingual angioedema and ACE inhibition after alteplase treatment of stroke. M. D. Hill, T. Lye, H. Moss, P. A. Barber, A. M. Demchuk, N. J. Newcommon, T. L. Green, C. Kenney, A. Cole–Haskayne, A. M. Buchan. Neurology May 2003, 60 (9) 1525-1527; DOI: 10.1212/01.WNL.0000058840.66596.1A DISCLOSURES: No relevant relationships by Robert Caldera, source=Web Response No relevant relationships by Kristin Fless, source=Web Response No relevant relationships by Bilal Khan, source=Web Response No relevant relationships by Nirav Mistry, source=Web Response No relevant relationships by Vagram Ovnanian, source=Web Response No relevant relationships by Fariborz Rezai, source=Web Response No relevant relationships by Aditi Saha, source=Web Response No relevant relationships by Sohaib Tariq, source=Web Response No relevant relationships by Lalithaa Thirunavukarasu Murugan, source=Web Response No relevant relationships by Paul Yodice, source=Web Response