Intravenous Tenectaplase for Treatment of Cerebral Emboli Occurring during Catheter-Based Angiography

Thromboembolic complications occurring during diagnostic catheter-based angiography are infrequently encountered in clinical practice. There is limited literature pertaining to recommendations regarding the management of thromboembolic complications after diagnostic cerebral angiography. Several previous investigations have employed intra-arterial alteplase or urokinase for vessel recanalization, with suboptimal outcomes in regards to recanalization and disability (1Hähnel S. Schellinger P.D. Gutschalk A. et al.Local intra-arterial fibrinolysis of thromboemboli occurring during neuroendovascular procedures with recombinant tissue plasminogen activator.Stroke. 2003; 34: 1723-1728Crossref PubMed Scopus (39) Google Scholar). In this letter, the authors report a case in which intravenous (IV) tenecteplase (TNK) was used for treatment of intraprocedural cerebral emboli during catheter-based angiography. This study was exempt from institutional review board approval secondary to the single case nature of this report. A 51-year-old man with a history of obesity presented with recurrent transient left-sided numbness, tingling, and syncope. Computed tomography (CT) angiography demonstrated extreme tortuosity of the bilateral internal carotid arteries with possible stenosis. Aspirin and clopidogrel were recommended in addition to catheter-based angiography for characterization of tortuosity with possible stenosis. Angiography demonstrated severe bilateral internal carotid artery tortuosity without evidence of flow-limiting stenosis (Fig 1). Transluminal pressure recordings using a microcatheter proximal and distal to the tortuosity on the right side revealed a gradient of <5 mm Hg. Transluminal pressure gradient recordings were not possible on the left side owing to severity of the tortuosity. Transluminal pressure recordings were performed to assess the possible contribution of vessel tortuosity to the patient’s presenting symptoms. Neurologic examination before removal of the access sheath revealed new-onset aphasia and right hemiplegia, raising suspicion for thromboembolic complication secondary to arteriography (National Institutes of Health Stroke Scale score of 16). Repeat angiography demonstrated nonocclusive emboli in the distal branches of the left middle cerebral artery and left anterior cerebral artery, not previously identified on initial angiography (Fig 2). Owing to the presence of multiple emboli within the distal arteries, mechanical thrombectomy was not an option. Intra-arterial nicardipine (10 mg/4 mL at a concentration of 2.5 mg/mL) was administered. The sheath was left in place, and the patient underwent emergent CT angiography/CT perfusion imaging, which revealed no large vessel occlusion in the arteries but decreased regional cerebral blood flow and regional cerebral blood volume in a confluent distribution of the left middle cerebral artery (Fig 3). The patient was deemed a candidate for emergent IV thrombolytic therapy. The patient was administrated with IV TNK (0.25 mg/kg; TNKase; Genentech, San Francisco, California) as a bolus. The decision to administer IV TNK was based on a number of pharmacokinetic factors, including ability for rapid bolus administration without infusion, longer half-life and duration of action, rapid preparation time, and enhanced fibrin specificity and improved resistance to degradation compared with that of alteplase.Figure 3Computed tomography perfusion (cerebral blood flow) demonstrated a focal perfusion deficit in the left frontal region (arrow).View Large Image Figure ViewerDownload Hi-res image Download (PPT) The patient demonstrated partially regained speech and right-sided motor function 2 hours after administration of TNK, with complete symptom resolution of deficits after 12 hours (National Institutes of Health Stroke Scale score of 1). Post-TNK CT perfusion at 24 hours showed no regional cerebral blood flow perfusion abnormality (Fig 4) without evidence of emboli on a CT angiogram, and a magnetic resonance imaging diffusion weighted image revealed only a small area of restricted diffusion (Fig 5). Notably, there was no conclusive method to differentiate clot dissolution from effects of TNK versus intrinsic clot dissolution.Figure 5A follow-up 24-hour magnetic resonance imaging diffusion weighted image sequence demonstrated reduced ischemic changes (arrow).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Follow-up brain magnetic resonance imaging identified only a small region of subtle diffusion restriction within the cortex of the left inferior frontal lobe, with corresponding fluid-attenuated inversion recovery hyperintensity (Fig 4). The patient was continued on dual antiplatelet therapy and was ultimately discharged home without further issues. At the 30-day follow-up, the patient reported no further issues and had a modified Rankin scale (mRS) score of 0. Essential equipment used during endovascular procedures includes angiographic catheters, guide wires, and microcatheters. The risk of thromboembolic complications increases because of associated arterial injury and the thrombogenic characteristics of all essential equipment employed, creating a nidus for thrombosis (2Qureshi A.I. Luft A.R. Sharma M. Guterman L.R. Hopkins L.N. Prevention and treatment of thromboembolic and ischemic complications associated with endovascular procedures: part II—clinical aspects and recommendations.Neurosurgery. 2000; 46: 1360-1376Crossref PubMed Scopus (195) Google Scholar). Contrast agents promote clotting in catheters and syringes (2Qureshi A.I. Luft A.R. Sharma M. Guterman L.R. Hopkins L.N. Prevention and treatment of thromboembolic and ischemic complications associated with endovascular procedures: part II—clinical aspects and recommendations.Neurosurgery. 2000; 46: 1360-1376Crossref PubMed Scopus (195) Google Scholar). Treatment options include intra-arterial alteplase or urokinase, neither of which have demonstrated high rates of angiographic recanalization or clinical improvement (3Mazighi M. Serfaty J.M. Labreuche J. et al.Comparison of intravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and confirmed arterial occlusion (RECANALISE study): a prospective cohort study.Lancet Neurol. 2009; 8: 802-809Abstract Full Text Full Text PDF PubMed Scopus (250) Google Scholar). Hähnel et al (1Hähnel S. Schellinger P.D. Gutschalk A. et al.Local intra-arterial fibrinolysis of thromboemboli occurring during neuroendovascular procedures with recombinant tissue plasminogen activator.Stroke. 2003; 34: 1723-1728Crossref PubMed Scopus (39) Google Scholar) have reported on 9 patients who experienced thromboembolic complications during neuroendovascular procedures and were treated with intra-arterial alteplase (maximum dose of 0.9 mg/kg). Successful angiographic recanalization was seen in 4 of the 9 patients, and all 9 patients presented infarction on follow-up imaging. Ischemic stroke was fatal in 2 patients, 4 patients had moderate disabilities with an mRS score of 1–3, and 3 patients were severely disabled with an mRS score of 4 at 3 months after intra-arterial alteplase treatment (1Hähnel S. Schellinger P.D. Gutschalk A. et al.Local intra-arterial fibrinolysis of thromboemboli occurring during neuroendovascular procedures with recombinant tissue plasminogen activator.Stroke. 2003; 34: 1723-1728Crossref PubMed Scopus (39) Google Scholar). The composition of the thrombus formed during endovascular procedures is possibly different from that of a spontaneously formed thrombus (4Qureshi A.I. Editorial comment—thromboembolic events during neuroendovascular procedures.Stroke. 2003; 34: 1728-1729Crossref PubMed Scopus (7) Google Scholar). Platelet activation and aggregation occur at the surface of endovascular devices and site of intimal injury within the arteries, and thrombus formation related to endovascular procedures may be platelet-rich and, therefore, more resistant to thrombolytic therapy, but could be amenable to platelet disaggregation treatments. IV TNK was superior to IV alteplase in a multicenter, prospective randomized study (5Campbell B.C.V. Mitchell P.J. Churilov L. et al.TNK InvestigatorsTenecteplase versus alteplase before thrombectomy for ischemic stroke.N Engl J Med. 2018; 378: 1573-1582Crossref PubMed Scopus (385) Google Scholar) that randomly assigned 202 patients with ischemic stroke who presented with large arterial occlusion and were eligible to undergo thrombectomy to receive IV TNK or IV alteplase within 4.5 hours after symptom onset. The primary outcome was reperfusion of >50% of the involved ischemic territory or absence of a retrievable thrombus, which occurred in 22% and 10% of the patients treated with IV TNK and IV alteplase, respectively. Moreover, the median mRS score was lower in patients treated with IV TNK than in those treated with IV alteplase. The case described in this letter presents the emergent use of IV TNK in a patient with intraprocedural emboli secondary to catheter-based angiography when mechanical thrombectomy was not an option.