1194

Abstract

Introduction: Alteplase (Activase®) is a recombinant tissue plasminogen activator (tPA) which has been shown to improve outcomes in acute ischemic stroke and has a low adverse effect profile. The complication of orolingual angioedema has been noted, but a cause and effect relationship has not been established. This life-threatening effect has been reported in 1.3-5% of stroke patients treated with tPA. Although cases of angioedema have been documented in patients not receiving angiotensin converting enzyme inhibitors (ACE-I), it appears patients receiving ACE-I may be at an increased risk of developing angioedema after tPA administration. This increased risk appears to be due to the generation of plasmin leading to an increase in bradykinin. Case report:A 66 year old, 112 kg, Hispanic male was brought in by ambulance with left sided weakness, facial droop, and slurred speech. The patient presented to the emergency department (ED) approximately 1.5 hours after the initial manifestation of symptoms. The patient's general appearance was lethargic, but alert and oriented x3 with coherent speech. Past medical history was significant only for hypertension; he did not smoke or drink. His home medications were as follows: lisinopril 40mg po daily, spironolactone 25mg po twice daily, aspirin 81mg po daily, amlodipine 10mg po daily. He reported no known allergies. The patient reported taking these medications chronically and consistently. Vital signs upon presentation to the ED were as follows: Temperature-97.6°F; Pulse-65 beats/min; Blood Pressure-119/72 mmHg; O2 Saturation-99%. Lab values were within normal limits except: Albumin-3.2 g/dL(0.2-1); Hemoglobin-11.6 g/dL(13-17); Hematocrit-34% (39-50). An initial CT of the head without contrast was obtained showing microvascular changes in the supratentorial white matter, not hemorrhage, nor midline shift. The patient's NIHSS score was calculated to be 20, and the patient fulfilled all criteria for alteplase administration. Alteplase was initiated per protocol as a 9mg IV bolus over 1 minute, then as 81mg IV infusion over 60 minutes. Approximately 1.5 hours after initiation, the patient notified ED staff of lip swelling. The patient was monitored and shortly thereafter the swelling appeared to worsen. Due to the risk of laryngeal edema, the decision was made to intubate and initiate treatment with methylprednisolone 125mg IVx1 and diphenhydramine 50mg IVx1. The patient was transferred to the medical intensive care unit for further follow up. The patient received standing diphenhydramine 25mg IV every 6 hours and dexamethasone 4mg IV every 6 hours. Within 48 hours after initial presentation the patient's angioedema resolved, leading to extubation and discontinuation of dexamethasone and diphenhydramine. The Naranjo algorithm score was calculated and yielded a score of 7 or a probable cause. Upon further workup, an MRI of the head showed a right thalamic infarct without hemorrhage or mass, however, an echocardiogram with bubble study discovered an inter-atrial shunt (PFO). Other evaluations of note were: lipid panel, Protein S activity, Factor V Leiden, and a Lupus Anticoagulant panel, all of which returned unremarkable. The cause of the infarct was determined to be due to a paradoxical embolus stemming from the PFO. The patient did not suffer any negative neurologic sequelae. Discussion: Angioedema is a rare effect of tPA administration, however, ACE-I therapy is known to be associated with angioedema. It is suggested that the mechanism for ACE-I induced angioedema is related to bradykinin accumulation. More specifically, ACE-I's inhibit the kinase enzyme responsible for the metabolism of bradykinin. The mechanism for tPA induced angioedema appears to be due to the generation of plasmin, a protease that cleaves bradykinin from a high molecular weight kininogen. The concomitant use of ACE-I appears to make patients susceptible to angioedema due to baseline higher accumulations of bradykinin.