Lower extremity arterial embolism after intravenous thrombolysis for acute ischemic stroke

Lower extremity arterial embolism after intravenous thrombolysis for acute ischemic stroke | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Lower extremity arterial embolism after intravenous thrombolysis for acute ischemic stroke Chaowei Xu, Qian Li, Jian Chen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4500755/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Early embolic events may be a rare complication following intravenous thrombolysis for acute ischemic stroke (AIS). Case presentation: We present two cases of lower extremity arterial embolism occurring shortly after intravenous thrombolysis. Both patients experienced acute occlusion of large arteries and atrial fibrillation and were diagnosed with cardioembolic stroke. The first case was a 49-year-old woman who presented with left limb paralysis. Thrombolysis with alteplase was performed, and five days later, she experienced a lower extremity arterial embolism. The second patient was a 64-year-old man who presented with right limb paralysis. Thrombolysis was performed, and three days later, he experienced a lower extremity arterial embolism. Conclusion Early embolic events may occur following intravenous thrombolysis for AIS, especially in patients with cardioembolic stroke; we should pay attention to this potential complication. Acute ischemic stroke Intravenous thrombolysis Early embolic events Atrial fibrillation Lower extremity arterial embolism Figures Figure 1 Figure 2 Background Acute ischemic stroke (AIS) is a disabling and potentially life-threatening condition, and the prompt administration of intravenous recombinant tissue-type plasminogen activator to suitable patients remains the cornerstone of early AIS treatment [ 1 ]. When it comes to intravenous thrombolysis, clinicians always pay attention to potential side effects such as bleeding, reperfusion injury, and allergic reactions [ 2 ]. However, early embolic events are often underestimated despite their potential fatality. Here, we present two cases of lower extremity arterial thrombosis occurring shortly after intravenous thrombolysis for AIS. Case presentation Case 1 A 49-year-old woman was admitted to the emergency department due to left limb paralysis lasting three hours. The patient had a history of hypertension and diabetes mellitus, with no history of heart disease. She denied the use of any medications. Physical examination showed drowsiness, dysphasia, bilateral eyeball gaze to the right, shallow left nasolabial fold, left tongue muscle weakness, left limb muscle strength was 0/5 on the MRC scale, left lateral hypalgesia, and a positive Babinski sign on the left side. Atrial fibrillation was detected upon auscultation of the heart. The National Institutes of Health Stroke Scale (NIHSS) scored 15 points. Laboratory tests were normal, including complete blood count, biochemistry, coagulation factors, and troponin. Cranial arterial computed tomography (CTA) revealed occlusion of the right middle cerebral artery (Fig. 1 A). The electrocardiogram indicated atrial fibrillation. Intravenous alteplase (49.5 mg; 0.9 mg/kg) was administered 230 minutes after symptom onset, resulting in rapid improvement with an NIHSS score of two post-thrombolytic therapy. Aspirin (200 mg/day) was initiated 24 hours after thrombolysis. Cranial magnetic resonance arteriography was performed on the third day, which showed recanalization of the right middle cerebral artery (Fig. 1 B). She was diagnosed with a cardioembolic stroke. On day five following admission, the patient experienced sudden onset pain in his right lower limb, pallor of the skin, decreased cutaneous temperature, and absence of a pulse in the right dorsal pedis artery. Lower extremity CTA revealed iliac artery thrombosis (Fig. 1 C). Transthoracic echocardiography was performed, and no thrombus was found in the heart. Lower extremity arterial thrombectomy under local anesthesia successfully removed a dark red thrombus measuring approximately 0.5 cm, restoring normal blood flow in the affected limb. Finally, the patient’s condition improved, and he was discharged with long-term anticoagulation therapy with warfarin. Cranial CTA revealed occlusion of the right middle cerebral artery (A). Cranial magnetic resonance arteriography revealed recanalization of the right middle cerebral artery (B). Lower extremity CTA revealed iliac artery thrombosis (C). Case 2 A 64-year-old man presented to the emergency department with right limb paralysis lasting one hour. He had no history of hypertension, diabetes mellitus, or heart disease. He denied taking any medications. Physical examination revealed clear consciousness, mixed aphasia, dysphasia, bilateral eyeball gaze to the left, shallow right nasolabial fold, right tongue muscle weakness, right limb muscle strength was 1/5 on the MRC scale, right lateral hypalgesia, and a positive Babinski sign on the right side. Atrial fibrillation was detected upon auscultation of the heart. The NIHSS score was 17 points. Laboratory tests were normal, including complete blood count, biochemistry, coagulation factors, and troponin. Cranial CTA revealed occlusion of the left middle cerebral artery (Fig. 2 A). The electrocardiogram indicated atrial fibrillation. Intravenous alteplase (54 mg; 0.9 mg/kg) was administered 160 minutes after symptom onset, resulting in rapid improvement with an NIHSS score of two points post-thrombolytic therapy. Aspirin (200 mg/day) was initiated 24 hours after thrombolysis. He was diagnosed with a cardioembolic stroke. On day three following admission, the patient had a sudden onset of signs and symptoms of a right lower extremity arterial embolism similar to that of the first patient. Lower extremity CTA revealed iliac artery thrombosis (Fig. 2 B). Transthoracic echocardiography was performed, and no thrombus was found in the heart. Lower extremity arterial thrombectomy under local anesthesia successfully removed a dark red thrombus measuring approximately 0.5 cm, restoring normal blood flow in the affected limb. The patient’s condition improved, and he was discharged with long-term anticoagulation therapy with warfarin. One month later, an outpatient cranial MR was completed, which showed the recanalization of the patient’s left middle cerebral artery (Fig. 2 C). Cranial CTA revealed occlusion of the left middle cerebral artery (A). Lower extremity CTA revealed iliac artery thrombosis (B). Cranial MR showed recanalization of the left middle cerebral artery (C). Discussion and conclusion AIS is the most common type of stroke, accounting for approximately 70% of all strokes; intravenous thrombolysis and mechanical thrombectomy are the most critical measures to restore blood flow [ 3 ]. In thrombolytic therapy, clinicians usually pay attention to bleeding, reperfusion injury, and drug allergy. We often fail to focus on early embolic events, which can also be fatal. In the report, both patients had acute occlusion of large arteries and atrial fibrillation; neurological symptoms improved rapidly after intravenous thrombolytic therapy, and imaging examination showed arterial recanalization. They were diagnosed with cardioembolic stroke. Unfortunately, the patients developed a lower extremity arterial embolism in a short period. There have been some reports of re-embolism after intravenous thrombolysis in patients with AIS involving contralateral cerebral, coronary, pulmonary, and renal arteries [ 4 – 6 ]. The cases reported in the literature were similar to those presented by us, with satisfactory results of intravenous thrombolysis and rapid improvement in neurological function. However, early embolic events occurred shortly after that. Awadh et al.speculated that early embolic events in patients receiving intravenous thrombolysis were related to the presence of atrial fibrillation, with the disintegration of pre-existing thrombosis in the atrium [ 7 ]. Derex et al. reported that 2.7% of thrombolytic patients had cardiac thrombosis and no early embolism recurrence [ 8 ]. Echocardiography could not be completed before intravenous thrombolysis due to time limitations. There was no guideline-recommended echocardiography to exclude cardiac thrombosis before intravenous thrombolysis. Here, neither of our patients completed echocardiography before thrombolytic therapy. It was uncertain whether embolism recurrence was attributed to the disintegration and migration of an existing thrombus. Doepp et al. speculated that the occurrence of early embolic events after thrombolytic therapy may be caused by secondary hypercoagulability [ 9 ]. Drugs, including venous and arterial thrombotic events, may play an important role in thrombosis [ 10 ]. The mechanisms include drug-induced endothelial injury, resulting in platelet adhesion and thrombosis; drug-decreased secretion of procoagulant and anticoagulant of endothelial cells; drug alters the balance between different coagulation factors. Anticoagulation therapy can reduce thrombotic events in patients with cardioembolic stroke. Anticoagulation initiation is controversial, and the optimal timing and therapeutic agents have yet to be thoroughly studied. The European Heart Rhythm Society practice guidelines for NOAC in patients with atrial fibrillation have refined the timing of anticoagulation therapy after ischemic stroke and recommended the “1-3-6-12” rule [ 11 ]. Despite the non-statistically significant results of the ELAN trial, they provide numerical confirmation of the safety and potential clinical benefit of early resumption of anticoagulation. This evidence guides clinicians in deciding the early resumption of anticoagulation [ 12 ]. In conclusion, early embolic events may occur after intravenous thrombolysis for AIS, which can affect patient outcomes. We should pay attention to early embolic events after thrombolysis, especially in patients with cardioembolic stroke. Abbreviations AIS: Acute ischemic stroke NIHSS: National institutes of health stroke scale CTA: Computed tomography MR: Magnetic resonance NOAC: Novel oral anticoagulants Declarations Acknowledgments We acknowledge the vascular surgeons for their contributions to the cases. Author contributions CWX and QL drafted the manuscript; QL collected patient information; JC interpreted the data and edited the manuscript. All authors read and approved the final manuscript. Funding No funding was received to assist with the preparation of this manuscript. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate The studies involving humans were approved by the Ethics Committee of Jinhua Central Hospital. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article. Consent for publication Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. Competing interests The authors declare that they have no competing interests. References Wardlaw JM, Murray V, Berge E, del Zoppo GJ. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev. 2014;2014(7):CD000213. Balami JS, Sutherland BA, Buchan AM. Complications associated with recombinant tissue plasminogen activator therapy for acute ischaemic stroke. CNS Neurol Disord Drug Targets. 2013;12(2):155–69. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46–46110. Mehdiratta M, Murphy C, Al-Harthi A, Teal PA. Myocardial infarction following t-PA for acute stroke. Can J Neurol Sci. 2007;34(4):417–20. Delgado MG, Mauri G, Vega J. Massive pulmonary thromboembolism after intravenous stroke thrombolysis. BMJ Case Rep. 2012;2012:bcr1020115008. Tanaka K, Ohara T, Ishigami A, Ikeda Y, Matsushige T, Satow T, et al. Fatal multiple systemic emboli after intravenous thrombolysis for cardioembolic stroke. J Stroke Cerebrovasc Dis. 2014;23(2):395–7. Awadh M, MacDougall N, Santosh C, Teasdale E, Baird T, Muir KW. Early recurrent ischemic stroke complicating intravenous thrombolysis for stroke: incidence and association with atrial fibrillation. Stroke. 2010;41(9):1990–5. Derex L, Nighoghossian N, Perinetti M, Honnorat J, Trouillas P. Thrombolytic therapy in acute ischemic stroke patients with cardiac thrombus. Neurology. 2001;57(11):2122–5. Doepp F, Sanad W, Schreiber SJ, Baumann G, Borges AC. Left ventricular apical thrombus after systemic thrombolysis with recombinant tissue plasminogen activator in a patient with acute ischemic stroke. Cardiovasc Ultrasound. 2005;3:14. Ramot Y, Nyska A, Spectre G. Drug-induced thrombosis: an update. Drug Saf. 2013;36(8):585–603. Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J. 2018;39(16):1330–93. Fischer U, Koga M, Strbian D, Branca M, Abend S, Trelle S, et al. Early versus Later Anticoagulation for Stroke with Atrial Fibrillation. N Engl J Med. 2023;388(26):2411–21. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4500755","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":310050567,"identity":"d24405d8-ed81-4c73-80a7-0c27368c799b","order_by":0,"name":"Chaowei Xu","email":"","orcid":"","institution":"Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Chaowei","middleName":"","lastName":"Xu","suffix":""},{"id":310050568,"identity":"c6671a1b-46a8-4832-88a5-fd8248aa21b7","order_by":1,"name":"Qian Li","email":"","orcid":"","institution":"Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Qian","middleName":"","lastName":"Li","suffix":""},{"id":310050569,"identity":"ffdc02c8-79c7-4b2a-a97d-d350bc48068c","order_by":2,"name":"Jian Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAApUlEQVRIiWNgGAWjYBACxmYQ0WDDw8/fQJqWNBnJGQdIsqrhsI1BQwKRqpnbmZ89+LnjPI8BwwHGDx9ziHIYm7lh75nbPObMDcySM7cRpYXBTJqx7TaPZcMBNmZe4rSwfwNqOcdjcCCBaC08IFsOkKalTLK3LZlHcsbBZuL8Yth/fJvEzzY7e37+5oMfPhKlpQFhYQNOVShAnjhlo2AUjIJRMKIBAI6vMnL5VjA1AAAAAElFTkSuQmCC","orcid":"","institution":"Zhejiang University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Jian","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2024-05-30 06:25:43","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4500755/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4500755/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":58385650,"identity":"cd55ca39-5467-4b3b-aeff-157115ea8436","added_by":"auto","created_at":"2024-06-14 18:41:11","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":91603,"visible":true,"origin":"","legend":"\u003cp\u003eCranial CTA revealed occlusion of the right middle cerebral artery (A). Cranial magnetic resonance arteriography revealed recanalization of the right middle cerebral artery (B). Lower extremity CTA revealed iliac artery thrombosis (C).\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4500755/v1/9c73e4355d779ce9a6fba5da.jpg"},{"id":58385649,"identity":"4935d27e-9542-4049-8d6d-87740469f5bb","added_by":"auto","created_at":"2024-06-14 18:41:11","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":69895,"visible":true,"origin":"","legend":"\u003cp\u003eCranial CTA revealed occlusion of the left middle cerebral artery (A). Lower extremity CTA revealed iliac artery thrombosis (B). Cranial MR showed recanalization of the left middle cerebral artery (C).\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4500755/v1/1ff99c94fbef7ccea81e6066.jpg"},{"id":58606047,"identity":"fbd8d25b-d7dd-4509-9bcb-312e1133f0f5","added_by":"auto","created_at":"2024-06-18 20:06:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":404288,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4500755/v1/ab3e246a-425e-464c-b97b-3ee5a696f68e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Lower extremity arterial embolism after intravenous thrombolysis for acute ischemic stroke","fulltext":[{"header":"Background","content":"\u003cp\u003eAcute ischemic stroke (AIS) is a disabling and potentially life-threatening condition, and the prompt administration of intravenous recombinant tissue-type plasminogen activator to suitable patients remains the cornerstone of early AIS treatment [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. When it comes to intravenous thrombolysis, clinicians always pay attention to potential side effects such as bleeding, reperfusion injury, and allergic reactions [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, early embolic events are often underestimated despite their potential fatality. Here, we present two cases of lower extremity arterial thrombosis occurring shortly after intravenous thrombolysis for AIS.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eCase 1\u003c/h2\u003e \u003cp\u003eA 49-year-old woman was admitted to the emergency department due to left limb paralysis lasting three hours. The patient had a history of hypertension and diabetes mellitus, with no history of heart disease. She denied the use of any medications. Physical examination showed drowsiness, dysphasia, bilateral eyeball gaze to the right, shallow left nasolabial fold, left tongue muscle weakness, left limb muscle strength was 0/5 on the MRC scale, left lateral hypalgesia, and a positive Babinski sign on the left side. Atrial fibrillation was detected upon auscultation of the heart. The National Institutes of Health Stroke Scale (NIHSS) scored 15 points. Laboratory tests were normal, including complete blood count, biochemistry, coagulation factors, and troponin. Cranial arterial computed tomography (CTA) revealed occlusion of the right middle cerebral artery (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). The electrocardiogram indicated atrial fibrillation. Intravenous alteplase (49.5 mg; 0.9 mg/kg) was administered 230 minutes after symptom onset, resulting in rapid improvement with an NIHSS score of two post-thrombolytic therapy. Aspirin (200 mg/day) was initiated 24 hours after thrombolysis. Cranial magnetic resonance arteriography was performed on the third day, which showed recanalization of the right middle cerebral artery (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). She was diagnosed with a cardioembolic stroke.\u003c/p\u003e \u003cp\u003eOn day five following admission, the patient experienced sudden onset pain in his right lower limb, pallor of the skin, decreased cutaneous temperature, and absence of a pulse in the right dorsal pedis artery. Lower extremity CTA revealed iliac artery thrombosis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). Transthoracic echocardiography was performed, and no thrombus was found in the heart. Lower extremity arterial thrombectomy under local anesthesia successfully removed a dark red thrombus measuring approximately 0.5 cm, restoring normal blood flow in the affected limb. Finally, the patient\u0026rsquo;s condition improved, and he was discharged with long-term anticoagulation therapy with warfarin.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eCranial CTA revealed occlusion of the right middle cerebral artery (A). Cranial magnetic resonance arteriography revealed recanalization of the right middle cerebral artery (B). Lower extremity CTA revealed iliac artery thrombosis (C).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCase 2\u003c/h3\u003e\n\u003cp\u003eA 64-year-old man presented to the emergency department with right limb paralysis lasting one hour. He had no history of hypertension, diabetes mellitus, or heart disease. He denied taking any medications. Physical examination revealed clear consciousness, mixed aphasia, dysphasia, bilateral eyeball gaze to the left, shallow right nasolabial fold, right tongue muscle weakness, right limb muscle strength was 1/5 on the MRC scale, right lateral hypalgesia, and a positive Babinski sign on the right side. Atrial fibrillation was detected upon auscultation of the heart. The NIHSS score was 17 points. Laboratory tests were normal, including complete blood count, biochemistry, coagulation factors, and troponin. Cranial CTA revealed occlusion of the left middle cerebral artery (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). The electrocardiogram indicated atrial fibrillation. Intravenous alteplase (54 mg; 0.9 mg/kg) was administered 160 minutes after symptom onset, resulting in rapid improvement with an NIHSS score of two points post-thrombolytic therapy. Aspirin (200 mg/day) was initiated 24 hours after thrombolysis. He was diagnosed with a cardioembolic stroke.\u003c/p\u003e \u003cp\u003eOn day three following admission, the patient had a sudden onset of signs and symptoms of a right lower extremity arterial embolism similar to that of the first patient. Lower extremity CTA revealed iliac artery thrombosis (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). Transthoracic echocardiography was performed, and no thrombus was found in the heart. Lower extremity arterial thrombectomy under local anesthesia successfully removed a dark red thrombus measuring approximately 0.5 cm, restoring normal blood flow in the affected limb. The patient\u0026rsquo;s condition improved, and he was discharged with long-term anticoagulation therapy with warfarin. One month later, an outpatient cranial MR was completed, which showed the recanalization of the patient\u0026rsquo;s left middle cerebral artery (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eCranial CTA revealed occlusion of the left middle cerebral artery (A). Lower extremity CTA revealed iliac artery thrombosis (B). Cranial MR showed recanalization of the left middle cerebral artery (C).\u003c/p\u003e"},{"header":"Discussion and conclusion","content":"\u003cp\u003eAIS is the most common type of stroke, accounting for approximately 70% of all strokes; intravenous thrombolysis and mechanical thrombectomy are the most critical measures to restore blood flow [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In thrombolytic therapy, clinicians usually pay attention to bleeding, reperfusion injury, and drug allergy. We often fail to focus on early embolic events, which can also be fatal.\u003c/p\u003e \u003cp\u003eIn the report, both patients had acute occlusion of large arteries and atrial fibrillation; neurological symptoms improved rapidly after intravenous thrombolytic therapy, and imaging examination showed arterial recanalization. They were diagnosed with cardioembolic stroke. Unfortunately, the patients developed a lower extremity arterial embolism in a short period. There have been some reports of re-embolism after intravenous thrombolysis in patients with AIS involving contralateral cerebral, coronary, pulmonary, and renal arteries [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The cases reported in the literature were similar to those presented by us, with satisfactory results of intravenous thrombolysis and rapid improvement in neurological function. However, early embolic events occurred shortly after that.\u003c/p\u003e \u003cp\u003eAwadh et al.speculated that early embolic events in patients receiving intravenous thrombolysis were related to the presence of atrial fibrillation, with the disintegration of pre-existing thrombosis in the atrium [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Derex et al. reported that 2.7% of thrombolytic patients had cardiac thrombosis and no early embolism recurrence [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Echocardiography could not be completed before intravenous thrombolysis due to time limitations. There was no guideline-recommended echocardiography to exclude cardiac thrombosis before intravenous thrombolysis. Here, neither of our patients completed echocardiography before thrombolytic therapy. It was uncertain whether embolism recurrence was attributed to the disintegration and migration of an existing thrombus.\u003c/p\u003e \u003cp\u003eDoepp et al. speculated that the occurrence of early embolic events after thrombolytic therapy may be caused by secondary hypercoagulability [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Drugs, including venous and arterial thrombotic events, may play an important role in thrombosis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The mechanisms include drug-induced endothelial injury, resulting in platelet adhesion and thrombosis; drug-decreased secretion of procoagulant and anticoagulant of endothelial cells; drug alters the balance between different coagulation factors.\u003c/p\u003e \u003cp\u003eAnticoagulation therapy can reduce thrombotic events in patients with cardioembolic stroke. Anticoagulation initiation is controversial, and the optimal timing and therapeutic agents have yet to be thoroughly studied. The European Heart Rhythm Society practice guidelines for NOAC in patients with atrial fibrillation have refined the timing of anticoagulation therapy after ischemic stroke and recommended the \u0026ldquo;1-3-6-12\u0026rdquo; rule [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Despite the non-statistically significant results of the ELAN trial, they provide numerical confirmation of the safety and potential clinical benefit of early resumption of anticoagulation. This evidence guides clinicians in deciding the early resumption of anticoagulation [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn conclusion, early embolic events may occur after intravenous thrombolysis for AIS, which can affect patient outcomes. We should pay attention to early embolic events after thrombolysis, especially in patients with cardioembolic stroke.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAIS: Acute ischemic stroke\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNIHSS: National institutes of health stroke scale\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCTA: Computed tomography\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMR: Magnetic resonance\u003c/p\u003e\n\u003cp\u003eNOAC: Novel oral anticoagulants\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe acknowledge the vascular surgeons for their contributions to the cases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCWX and QL drafted the manuscript; QL collected patient information; JC interpreted the data and edited the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received to assist with the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe studies involving humans were approved by the Ethics Committee of Jinhua Central Hospital. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this Case report and any accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWardlaw JM, Murray V, Berge E, del Zoppo GJ. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev. 2014;2014(7):CD000213.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBalami JS, Sutherland BA, Buchan AM. Complications associated with recombinant tissue plasminogen activator therapy for acute ischaemic stroke. CNS Neurol Disord Drug Targets. 2013;12(2):155\u0026ndash;69.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePowers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46\u0026ndash;46110.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMehdiratta M, Murphy C, Al-Harthi A, Teal PA. Myocardial infarction following t-PA for acute stroke. Can J Neurol Sci. 2007;34(4):417\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDelgado MG, Mauri G, Vega J. Massive pulmonary thromboembolism after intravenous stroke thrombolysis. BMJ Case Rep. 2012;2012:bcr1020115008.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTanaka K, Ohara T, Ishigami A, Ikeda Y, Matsushige T, Satow T, et al. Fatal multiple systemic emboli after intravenous thrombolysis for cardioembolic stroke. J Stroke Cerebrovasc Dis. 2014;23(2):395\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAwadh M, MacDougall N, Santosh C, Teasdale E, Baird T, Muir KW. Early recurrent ischemic stroke complicating intravenous thrombolysis for stroke: incidence and association with atrial fibrillation. Stroke. 2010;41(9):1990\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDerex L, Nighoghossian N, Perinetti M, Honnorat J, Trouillas P. Thrombolytic therapy in acute ischemic stroke patients with cardiac thrombus. Neurology. 2001;57(11):2122\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDoepp F, Sanad W, Schreiber SJ, Baumann G, Borges AC. Left ventricular apical thrombus after systemic thrombolysis with recombinant tissue plasminogen activator in a patient with acute ischemic stroke. Cardiovasc Ultrasound. 2005;3:14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRamot Y, Nyska A, Spectre G. Drug-induced thrombosis: an update. Drug Saf. 2013;36(8):585\u0026ndash;603.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSteffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J. 2018;39(16):1330\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFischer U, Koga M, Strbian D, Branca M, Abend S, Trelle S, et al. Early versus Later Anticoagulation for Stroke with Atrial Fibrillation. N Engl J Med. 2023;388(26):2411\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Acute ischemic stroke, Intravenous thrombolysis, Early embolic events, Atrial fibrillation, Lower extremity arterial embolism","lastPublishedDoi":"10.21203/rs.3.rs-4500755/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4500755/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eEarly embolic events may be a rare complication following intravenous thrombolysis for acute ischemic stroke (AIS).\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e \u003cp\u003eWe present two cases of lower extremity arterial embolism occurring shortly after intravenous thrombolysis. Both patients experienced acute occlusion of large arteries and atrial fibrillation and were diagnosed with cardioembolic stroke. The first case was a 49-year-old woman who presented with left limb paralysis. Thrombolysis with alteplase was performed, and five days later, she experienced a lower extremity arterial embolism. The second patient was a 64-year-old man who presented with right limb paralysis. Thrombolysis was performed, and three days later, he experienced a lower extremity arterial embolism.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eEarly embolic events may occur following intravenous thrombolysis for AIS, especially in patients with cardioembolic stroke; we should pay attention to this potential complication.\u003c/p\u003e","manuscriptTitle":"Lower extremity arterial embolism after intravenous thrombolysis for acute ischemic stroke","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-14 18:41:06","doi":"10.21203/rs.3.rs-4500755/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d03fa5b1-d4b5-4564-b506-decf6a38f482","owner":[],"postedDate":"June 14th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-18T20:06:16+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-14 18:41:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4500755","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4500755","identity":"rs-4500755","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}