{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:04:32Z","timestamp":1769731472729,"version":"3.49.0"},"reference-count":25,"publisher":"IMR Press","issue":"1","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union \u2013 NextGenerationEU. Recovery, Transformation, and Resilience Plan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rev. Neurol."],"abstract":"<jats:p>Background: There is considerable interest in the underlying mechanisms of cryptogenic stroke, with hypercoagulable states being widely studied. An elevated level of Factor VIII has been proposed as a potential prothrombotic marker associated with ischemic stroke. The aim of this study was to investigate the association between elevated Factor VIII levels and ischemic stroke and etiological subtype. Subjects and Methods: This retrospective observational study was conducted on subjects treated for ischemic stroke in the stroke unit of our institute between October 2018 and October 2023. Coagulative Factor VIII levels outside the acute phase (\u22653 months) were measured, with elevated levels defined as &gt;150%. Stroke etiologies (cryptogenic and non-cryptogenic: atherothrombotic, cardioembolic, lacunar, unusual, and coexistent causes), main cardiovascular risk factors, and prothrombotic biomarkers (protein C, protein S, antithrombin, anticardiolipin antibodies, anti-beta2-glycoprotein, lupus anticoagulant, and D-dimer) were recorded. Patients were categorized based on their level of coagulation Factor VIII (&gt;150% vs. \u2264150%). A comparative analysis was then conducted to assess differences associated with Factor VIII level. Results: A total of 68 patients were included, with a median age of 50.3 \u00b1 12.2 years and a predominance of males (66.2%). The most frequent etiology was cryptogenic stroke (54.4%), followed by atherothrombotic (13.2%) and unusual causes (11.8%). Elevated Factor VIII levels were observed in 41.2% of patients. No significant associations were found between elevated Factor VIII and cryptogenic stroke (p = 0.27), stroke subtype (p = 0.38), comorbidities, or other thrombophilia biomarkers. However, a weak correlation was observed between elevated Factor VIII and antithrombin levels outside the normal range (p = 0.039), and a significant association was found between Factor VIII levels and prior atrial fibrillation (AF, p = 0.04). Conclusions: Although a high coagulation Factor VIII level was frequently observed in patients with ischemic stroke, this was not associated with cryptogenic stroke in the present cohort. Further studies with a larger sample size are warranted to clarify whether elevated Factor VIII is independently associated with ischemic stroke subtype, and whether elevated levels are a secondary finding related to inflammatory or systemic factors.<\/jats:p>","DOI":"10.31083\/rn44168","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T12:16:11Z","timestamp":1769688971000},"source":"Crossref","is-referenced-by-count":0,"title":["Influence of Coagulation Factor VIII on Ischemic Stroke"],"prefix":"10.31083","volume":"81","author":[{"given":"Mar\u00eda Del Mar","family":"Mart\u00ednez-Salmer\u00f3n","sequence":"first","affiliation":[{"name":"Department of Neurology, Torrec\u00e1rdenas University Hospital, 04009 Almer\u00eda, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1162-4209","authenticated-orcid":true,"given":"Laura","family":"Amaya-Pascasio","sequence":"additional","affiliation":[{"name":"Department of Neurology, Torrec\u00e1rdenas University Hospital, 04009 Almer\u00eda, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1945-4435","authenticated-orcid":true,"given":"Patricia","family":"Mart\u00ednez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Neurology, Torrec\u00e1rdenas University Hospital, 04009 Almer\u00eda, Spain"},{"name":"Faculty of Health Science, Health Research Center (CEINSA), University of Almer\u00eda, 04120 Almer\u00eda, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1530-8791","authenticated-orcid":true,"given":"Antonio","family":"Arjona-Padillo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Torrec\u00e1rdenas University Hospital, 04009 Almer\u00eda, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Prendes CF, Rantner B, Hamwi T, Stana J, Feigin VL, Stavroulakis K, et al. Burden of Stroke in Europe: An Analysis of the Global Burden of Disease Study Findings From 2010 to 2019. Stroke. 2024; 55: 432\u2013442.","DOI":"10.1161\/STROKEAHA.122.042022"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Ohya Y, Matsuo R, Sato N, Irie F, Nakamura K, Wakisaka Y, et al. Causes of ischemic stroke in young adults versus non-young adults: A multicenter hospital-based observational study. PloS One. 2022; 17: e0268481.","DOI":"10.1371\/journal.pone.0268481"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Hart RG, Diener HC, Coutts SB, Easton JD, Granger CB, O\u2019Donnell MJ, et al. Embolic strokes of undetermined source: the case for a new clinical construct. The Lancet. Neurology. 2014; 13: 429\u2013438.","DOI":"10.1016\/S1474-4422(13)70310-7"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Kamphuisen PW, Eikenboom JC, Bertina RM. Elevated factor VIII levels and the risk of thrombosis. Arteriosclerosis, Thrombosis, and Vascular Biology. 2001; 21: 731\u2013738.","DOI":"10.1161\/01.atv.21.5.731"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Chang TR, Albright KC, Boehme AK, Dorsey A, Sartor EA, Kruse-Jarres R, et al. Factor VIII in the setting of acute ischemic stroke among patients with suspected hypercoagulable state. Clinical and Applied Thrombosis\/hemostasis: Official Journal of the International Academy of Clinical and Applied Thrombosis\/Hemostasis. 2014; 20: 124\u2013128.","DOI":"10.1177\/1076029613488936"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Rohmann JL, Huo S, Sperber PS, Piper SK, Rosendaal FR, Heuschmann PU, et al. Coagulation factor XII, XI, and VIII activity levels and secondary events after first ischemic stroke. Journal of Thrombosis and Haemostasis: JTH. 2020; 18: 3316\u20133324.","DOI":"10.1111\/jth.15092"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Harshfield EL, Sims MC, Traylor M, Ouwehand WH, Markus HS. The role of haematological traits in risk of ischaemic stroke and its subtypes. Brain: a Journal of Neurology. 2020; 143: 210\u2013221.","DOI":"10.1093\/brain\/awz362"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Siegler JE, Samai A, Albright KC, Boehme AK, Martin-Schild S. Factoring in Factor VIII With Acute Ischemic Stroke. Clinical and Applied Thrombosis\/hemostasis: Official Journal of the International Academy of Clinical and Applied Thrombosis\/Hemostasis. 2015; 21: 597\u2013602.","DOI":"10.1177\/1076029615571630"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Karttunen V, Alfthan G, Hiltunen L, Rasi V, Kervinen K, Kes\u00e4niemi YA, et al. Risk factors for cryptogenic ischaemic stroke. European Journal of Neurology. 2002; 9: 625\u2013632.","DOI":"10.1046\/j.1468-1331.2002.00464.x"},{"key":"ref10","unstructured":"D\u00edez Tejedor E, Fuentes B; Comit\u00e9 ad hoc del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Espa\u00f1ola de Neurolog\u00eda. Gu\u00eda para el diagn\u00f3stico y tratamiento del ictus. 1st edn. Sociedad Espa\u00f1ola de Neurolog\u00eda: Barcelona. 2006. (In Spanish)"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Catto AJ, Carter AM, Barrett JH, Bamford J, Rice PJ, Grant PJ. von Willebrand factor and factor VIII: C in acute cerebrovascular disease. Relationship to stroke subtype and mortality. Thrombosis and Haemostasis. 1997; 77: 1104\u20131108.","DOI":"10.1055\/s-0038-1656120"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Rumley A, Lowe GD, Sweetnam PM, Yarnell JW, Ford RP. Factor VIII, von Willebrand factor and the risk of major ischaemic heart disease in the Caerphilly Heart Study. British Journal of Haematology. 1999; 105: 110\u2013116.","DOI":"10.1046\/j.1365-2141.1999.01317.x"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"van der Meer FJ, Koster T, Vandenbroucke JP, Bri\u00ebt E, Rosendaal FR. The Leiden Thrombophilia Study (LETS). Thrombosis and Haemostasis. 1997; 78: 631\u2013635.","DOI":"10.1055\/s-0038-1657602"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Alam A, Doshi H, Patel DN, Patel K, James D, Almendral J. Myocardial infarction and factor VIII elevation in a 36-year-old man. Proceedings (Baylor University. Medical Center). 2021; 35: 93\u201395.","DOI":"10.1080\/08998280.2021.1973285"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Sabry Safan A, Hamid OA, Al-Mashdali A, AlSaud A, Al-Shokri S, Hamad A. Rare case of simultaneous cerebral artery and venous sinus thrombosis in the setting of elevated factor VIII and combined oral contraceptive pills. Clinical Case Reports. 2022; 10: e05560.","DOI":"10.1002\/ccr3.5560"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Deskins SJ, Mamone M, Luketich S, Jennings A, Downey S, Gelman J, et al. Acute Ischemic Stroke in an Eight-Year-Old Male With Elevated Factor VIII Activity and SARS-CoV-2 Antibodies. Cureus. 2022; 14: e24982.","DOI":"10.7759\/cureus.24982"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Gouse BM, Boehme AK, Monlezun DJ, Siegler JE, George AJ, Brag K, et al. New Thrombotic Events in Ischemic Stroke Patients with Elevated Factor VIII. Thrombosis. 2014; 2014: 302861.","DOI":"10.1155\/2014\/302861"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Kato Y, Takahashi S. Atrial Cardiopathy and Cryptogenic Stroke. Frontiers in Neurology. 2022; 13: 839398.","DOI":"10.3389\/fneur.2022.839398"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Nahab F, Sharashidze V, Liu M, Rathakrishnan P, El Jamal S, Duncan A, et al. Markers of coagulation and hemostatic activation aid in identifying causes of cryptogenic stroke. Neurology. 2020; 94: e1892\u2013e1899.","DOI":"10.1212\/WNL.0000000000009365"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Kamin Mukaz D, Gergi M, Koh I, Zakai NA, Judd SE, Sholzberg M, et al. Thrombo-inflammatory biomarkers and D-dimer in a biracial cohort study. Research and Practice in Thrombosis and Haemostasis. 2021; 5: e12632.","DOI":"10.1002\/rth2.12632"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Falcione S, Kamtchum-Tatuene J, Sykes G, Jickling GC. RNA expression studies in stroke: what can they tell us about stroke mechanism? Current Opinion in Neurology. 2020; 33: 24\u201329.","DOI":"10.1097\/WCO.0000000000000786"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Fern\u00e1ndez-P\u00e9rez I, Vallverd\u00fa-Prats M, Rey-\u00c1lvarez L, Giralt Steinhauer E, Ois A, Cuadrado-Godia E, et al. Circulating miRNAs Associated With 3-Month Outcome in Patients With Acute Ischemic Stroke. Neurology. 2025; 104: e210085.","DOI":"10.1212\/WNL.0000000000210085"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Wang Y, Su X, Leung GHD, Ren B, Zhang Q, Xiong Z, et al. Circulating microRNAs as diagnostic biomarkers for ischemic stroke: evidence from comprehensive analysis and real-world validation. International Journal of Medical Sciences. 2023; 20: 1009\u20131023.","DOI":"10.7150\/ijms.83963"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Sirachainan N, Boonyatarp M, Kadegasem P, Sasanakul W, Visudtibhan A, Natesirinilkul R, et al. High Factor VIII and Von Willebrand Factor Levels Are Not Risk Factors of Cryptogenic Arterial Ischemic Stroke in Thai Children. Journal of Child Neurology. 2015; 30: 1057\u20131059.","DOI":"10.1177\/0883073814541475"},{"key":"ref25","unstructured":"Orstavik KH, Magnus P, Reisner H, Berg K, Graham JB, Nance W. Factor VIII and factor IX in a twin population. Evidence for a major effect of ABO locus on factor VIII level. American Journal of Human Genetics. 1985; 37: 89\u2013101."}],"container-title":["Revista de Neurolog\u00eda"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/RN\/81\/1\/10.31083\/RN44168","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T12:16:17Z","timestamp":1769688977000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/RN\/81\/1\/10.31083\/RN44168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,26]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026]]}},"alternative-id":["S0210-0010(25)00092-1"],"URL":"https:\/\/doi.org\/10.31083\/rn44168","relation":{},"ISSN":["0210-0010","1576-6578"],"issn-type":[{"value":"0210-0010","type":"print"},{"value":"1576-6578","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,26]]},"article-number":"44168"}}