https://doi.org/10.4081/btvb.2024.117
Cancer-associated ischemic stroke: current knowledge and future directions
Submitted: 16 January 2024
Accepted: 4 March 2024
Published: 16 May 2024
Accepted: 4 March 2024
Abstract Views: 1034
PDF: 271
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Because cancer is a strong prothrombotic, there is an increased risk of thromboembolism, which includes ischemic stroke, especially in the first six to twelve months following a cancer diagnosis. The risk of ischemic stroke differs according to the location and stage of cancer. Given that the risk increases prior to a cancer diagnosis, stroke may be the initial sign of occult cancer. Although data on the risk, treatment, and outcomes of cancer-associated stroke are more limited than those on cancer-associated venous thromboembolism, the condition is still recognized as a thrombotic complication of cancer. Up to 10% of ischemic stroke patients also have a concurrent cancer diagnosis, and these patients seem to have higher short-term mortality and morbidity rates. With more people expected to survive longer after cancer treatment and an increasing number of cancer survivors, the burden of stroke among cancer patients is predicted to rise. This narrative review aims to provide an overview of the pathophysiologic mechanisms, treatment options, and epidemiology of ischemic stroke, including cancer screening for those who have cryptogenic (unexplained) stroke.
ASCOanswers. Cancer Survivorship. Practical and Trusted Information to Manage Life After Cancer from the American Society of Clinical Oncology. Available from: https://www.cancer.net/sites/cancer.net/files/cancer_survivorship.pdf (accessed on 20th October, 2018).
American Cancer Society. Cancer treatment & survivorship facts & figures 2016-2017. American Cancer Society 2016.
Henley SJ, Singh SD, King J, et al. Invasive cancer incidence and survival--United States, 2011. MMWR Morb Mortal Wkly Rep 2015;64:237-42.
DOI: https://doi.org/10.15585/mmwr.mm6449a1
Canadian Cancer Statistics Advisory Committee. Canadian Cancer Statistics 2-18. Toronto, ON: Canadian Cancer Society 2018. Available from: cancer.ca/Canacian-Cancer-Statistics-2018-EN (accessed on 10th October, 2018).
The Cancer Atlas. Available from: https://canceratlas.cancer.org/
Navi BB, Reiner AS, Kamel H, et al. Risk of Arterial Thromboembolism in Patients With Cancer. J Am Coll Cardiol 2017;70:926-38.
DOI: https://doi.org/10.1016/j.jacc.2017.06.047
Khan F, Tritschler T, Kahn SR, Rodger MA. Venous thromboembolism. Lancet 2021;398:64-77.
DOI: https://doi.org/10.1016/S0140-6736(20)32658-1
Hart RG, Catanese L, Perera KS, et al. Embolic stroke of undetermined source: a systematic review and clinical update. Stroke 2017;48:867-72.
DOI: https://doi.org/10.1161/STROKEAHA.116.016414
Verschoof MA, Groot AE, de Bruijn S, et al. Clinical Outcome After Endovascular Treatment in Patients With Active Cancer and Ischemic Stroke: A MR CLEAN Registry Substudy. Neurology 2022;98:e993-e1001.
Cestari DM, Weine DM, Panageas KS, et al. Stroke in patients with cancer: incidence and etiology. Neurology 2004;62: 2025-30.
DOI: https://doi.org/10.1212/01.WNL.0000129912.56486.2B
Graus F, Rogers LR, Posner JB. Cerebrovascular complications in patients with cancer. Medicine (Baltimore) 1985;64:16-35.
DOI: https://doi.org/10.1097/00005792-198501000-00002
Navi BB, Reiner AS, Kamel H, et al. Arterial thromboembolic events preceding the diagnosis of cancer in older persons. Blood 2019;133:781-9.
DOI: https://doi.org/10.1182/blood-2018-06-860874
Siegal DM, Cerasuolo JO, Carrier M, et al. A Population Cohort Study to Evaluate the Risk of Ischemic Stroke Among Individuals with a New Diagnosis of Cancer Compared to Matched Cancer-Free Controls: Impact of Prior Stroke History. Blood 2021;138:175.
DOI: https://doi.org/10.1182/blood-2021-151797
Navi BB, Reiner AS, Kamel H, et al. Association between incident cancer and subsequent stroke. Ann Neurol 2015;77: 291-300.
DOI: https://doi.org/10.1002/ana.24325
Koene RJ, Prizment AE, Blaes A, Konety SH. Shared Risk Factors in Cardiovascular Disease and Cancer. Circulation 2016;133:1104-14.
DOI: https://doi.org/10.1161/CIRCULATIONAHA.115.020406
Cutting S, Wettengel M, Conners JJ, et al. Three-Month Outcomes Are Poor in Stroke Patients with Cancer Despite Acute Stroke Treatment. J Stroke Cerebrovasc Dis 2017;26:809-15.
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2016.10.021
Navi BB, Singer S, Merkler AE, et al. Recurrent thromboembolic events after ischemic stroke in patients with cancer. Neurology 2014;83:26-33.
DOI: https://doi.org/10.1212/WNL.0000000000000539
Grilz E, Konigsbrugge O, Posch F, et al. Frequency, risk factors, and impact on mortality of arterial thromboembolism in patients with cancer. Haematologica 2018;103:1549-56.
DOI: https://doi.org/10.3324/haematol.2018.192419
Navi BB, Singer S, Merkler AE, et al. Cryptogenic subtype predicts reduced survival among cancer patients with ischemic stroke. Stroke 2014;45:2292-7.
DOI: https://doi.org/10.1161/STROKEAHA.114.005784
Lun R, Siegal D, Ramsay T, Dowlatshahi D. Cancer and stroke: What do we know and where do we go? Thromb Res 2022;219:133-40.
DOI: https://doi.org/10.1016/j.thromres.2022.09.014
Khorana AA, Mackman N, Falanga A, et al. Cancer-associated venous thromboembolism. Nat Rev Dis Primers 2022;8:11.
DOI: https://doi.org/10.1038/s41572-022-00336-y
Caine GJ, Stonelake PS, Lip GY, Kehoe ST. The hypercoagulable state of malignancy: pathogenesis and current debate. Neoplasia 2002;4:465-73.
DOI: https://doi.org/10.1038/sj.neo.7900263
Patmore S, Dhami SPS, O’Sullivan JM. Von Willebrand factor and cancer; metastasis and coagulopathies. J Thromb Haemost 2020;18:2444-56.
DOI: https://doi.org/10.1111/jth.14976
Ay C, Simanek R, Vormittag R, et al. High plasma levels of soluble P-selectin are predictive of venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS). Blood 2008;112:2703-8.
DOI: https://doi.org/10.1182/blood-2008-02-142422
Bang OY, Chung JW, Lee MJ, et al. Cancer Cell-Derived Extracellular Vesicles Are Associated with Coagulopathy Causing Ischemic Stroke via Tissue Factor-Independent Way: The OASIS-CANCER Study. PLoS One 2016;11: e0159170.
DOI: https://doi.org/10.1371/journal.pone.0159170
Navi BB, Mathias R, Sherman CP, et al. Cancer-Related Ischemic Stroke Has a Distinct Blood mRNA Expression Profile. Stroke 2019;50:3259-64.
DOI: https://doi.org/10.1161/STROKEAHA.119.026143
Nipu MAI, Kundu S, Alam SS, et al. Anticardiolipin Antibodies in Patients with Cancer: A Case-Control Study. Cancers (Basel) 2023;15.
DOI: https://doi.org/10.3390/cancers15072087
Pugliese L, Bernardini I, Pacifico E, et al. Antiphospholipid antibodies in patients with cancer. Int J Immunopathol Pharmacol 2006;19:879-88.
DOI: https://doi.org/10.1177/039463200601900417
Kungwankiattichai S, Nakkinkun Y, Owattanapanich W, Ruchutrakool T. High Incidence of Antiphospholipid Antibodies in Newly Diagnosed Patients With Lymphoma and a Proposed aPL Predictive Score. Clin Appl Thromb Hemost 2020;26:1076029620928392.
DOI: https://doi.org/10.1177/1076029620928392
Kansuttiviwat C, Niprapan P, Tantiworawit A, et al. Impact of antiphospholipid antibodies on thrombotic events in ambulatory cancer patients. PLoS One 2023;18:e0279450.
DOI: https://doi.org/10.1371/journal.pone.0279450
Schwarzbach CJ, Schaefer A, Ebert A, et al. Stroke and cancer: the importance of cancer-associated hypercoagulation as a possible stroke etiology. Stroke 2012;43:3029-34.
DOI: https://doi.org/10.1161/STROKEAHA.112.658625
Kim SG, Hong JM, Kim HY, et al. Ischemic stroke in cancer patients with and without conventional mechanisms: a multicenter study in Korea. Stroke 2010;41:798-801.
DOI: https://doi.org/10.1161/STROKEAHA.109.571356
Venepally NR, Arsanjani R, Agasthi P, et al. A New Insight Into Nonbacterial Thrombotic Endocarditis: A Systematic Review of Cases. Anatol J Cardiol 2022;26:743-9.
DOI: https://doi.org/10.5152/AnatolJCardiol.2022.1282
Itzhaki Ben Zadok O, Spectre G, Leader A. Cancer-associated non-bacterial thrombotic endocarditis. Thromb Res 2022;213:S127-S32.
DOI: https://doi.org/10.1016/j.thromres.2021.11.024
Deppisch LM, Fayemi AO. Non-bacterial thrombotic endocarditis: clinicopathologic correlations. Am Heart J 1976;92:723-9.
DOI: https://doi.org/10.1016/S0002-8703(76)80008-7
Hagen PT, Scholz DG, Edwards WD. Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts. Mayo Clin Proc 1984;59:17-20.
DOI: https://doi.org/10.1016/S0025-6196(12)60336-X
Iguchi Y, Kimura K, Kobayashi K, et al. Ischaemic stroke with malignancy may often be caused by paradoxical embolism. J Neurol Neurosurg Psychiatr 2006;77:1336-9.
DOI: https://doi.org/10.1136/jnnp.2006.092940
Hart RG, Diener HC, Coutts SB, et al. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol 2014;13:429-38.
DOI: https://doi.org/10.1016/S1474-4422(13)70310-7
Sacco RL, Ellenberg JH, Mohr JP, et al. Infarcts of undetermined cause: the NINCDS Stroke Data Bank. Ann Neurol 1989;25:382-90.
DOI: https://doi.org/10.1002/ana.410250410
Li L, Yiin GS, Geraghty OC, et al. Incidence, outcome, risk factors, and long-term prognosis of cryptogenic transient ischaemic attack and ischaemic stroke: a population-based study. Lancet Neurol 2015;14:903-13.
DOI: https://doi.org/10.1016/S1474-4422(15)00132-5
Ji R, Schwamm LH, Pervez MA, Singhal AB. Ischemic stroke and transient ischemic attack in young adults: risk factors, diagnostic yield, neuroimaging, and thrombolysis. JAMA Neurol 2013;70:51-7.
DOI: https://doi.org/10.1001/jamaneurol.2013.575
Wolf ME, Grittner U, Bottcher T, et al. Phenotypic ASCO Characterisation of Young Patients with Ischemic Stroke in the Prospective Multicentre Observational sifap1 Study. Cerebrovasc Dis 2015;40:129-35.
DOI: https://doi.org/10.1159/000434760
Rioux B, Touma L, Nehme A, et al. Frequency and predictors of occult cancer in ischemic stroke: A systematic review and meta-analysis. Int J Stroke 2021;16:12-9.
DOI: https://doi.org/10.1177/1747493020971104
Saver JL. Cryptogenic Stroke. N Engl J Med 2016;375:e26.
DOI: https://doi.org/10.1056/NEJMc1609156
May JE, Moll S. How I treat unexplained arterial thrombosis. Blood 2020;136:1487-98.
DOI: https://doi.org/10.1182/blood.2019000820
Gladstone DJ, Lindsay MP, Douketis J, et al. Canadian Stroke Best Practice Recommendations: Secondary Prevention of Stroke Update 2020. Can J Neurol Sci 2022;49:315-37.
DOI: https://doi.org/10.1017/cjn.2021.127
Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association. Stroke 2021;52:e364-e467.
DOI: https://doi.org/10.1161/STR.0000000000000375
Verhoeven JI, Fan B, Broeders MJM, et al. Association of Stroke at Young Age With New Cancer in the Years After Stroke Among Patients in the Netherlands. JAMA Netw Open 2023;6:e235002.
DOI: https://doi.org/10.1001/jamanetworkopen.2023.5002
Seystahl K, Gramatzki D, Wanner M, et al. A risk model for prediction of diagnosis of cancer after ischemic stroke. Sci Rep 2023;13:111.
DOI: https://doi.org/10.1038/s41598-022-26790-y
Robin P, Le Roux PY, Planquette B, et al. Limited screening with versus without (18)F-fluorodeoxyglucose PET/CT for occult malignancy in unprovoked venous thromboembolism: an open-label randomised controlled trial. Lancet Oncol 2016;17:193-9.
DOI: https://doi.org/10.1016/S1470-2045(15)00480-5
Owusu-Guha J, Guha A, Miller PE, et al. Contemporary utilization patterns and outcomes of thrombolytic administration for ischemic stroke among patients with cancer. Int J Stroke 2021;16:150-62.
DOI: https://doi.org/10.1177/1747493019895709
Ganesh A, Kashani N, Ospel JM, et al. Endovascular Therapy or Alteplase in Patients with Comorbidities: Insights from UNMASK EVT. Can J Neurol Sci 2021;48:77-86.
DOI: https://doi.org/10.1017/cjn.2020.158
Falanga A, Leader A, Ambaglio C, et al. EHA Guidelines on Management of Antithrombotic Treatments in Thrombocytopenic Patients With Cancer. Hemasphere 2022;6:e750.
DOI: https://doi.org/10.1097/HS9.0000000000000750
Hart RG, Sharma M, Mundl H, et al. Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source. N Engl J Med 2018;378:2191-201.
DOI: https://doi.org/10.1056/NEJMoa1802686
Diener HC, Sacco RL, Easton JD, et al. Dabigatran for Prevention of Stroke after Embolic Stroke of Undetermined Source. N Engl J Med 2019;380:1906-17.
DOI: https://doi.org/10.1056/NEJMoa1813959
Martinez-Majander N, Ntaios G, Liu YY, et al. Rivaroxaban versus aspirin for secondary prevention of ischaemic stroke in patients with cancer: a subgroup analysis of the NAVIGATE ESUS randomized trial. Eur J Neurol 2020;27:841-8.
DOI: https://doi.org/10.1111/ene.14172
Lee MJ, Chung JW, Ahn MJ, et al. Hypercoagulability and Mortality of Patients with Stroke and Active Cancer: The OASIS-CANCER Study. J Stroke 2017;19:77-87.
DOI: https://doi.org/10.5853/jos.2016.00570
Navi BB, Marshall RS, Bobrow D, et al. Enoxaparin vs Aspirin in Patients With Cancer and Ischemic Stroke: The TEACH Pilot Randomized Clinical Trial. JAMA Neurol 2018;75:379-81.
DOI: https://doi.org/10.1001/jamaneurol.2017.4211
Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med 2017;377:1319-30.
DOI: https://doi.org/10.1056/NEJMoa1709118
Anand SS, Hiatt W, Dyal L, et al. Low-dose rivaroxaban and aspirin among patients with peripheral artery disease: a meta-analysis of the COMPASS and VOYAGER trials. Eur J Prev Cardiol 2022;29:e181-e9.
DOI: https://doi.org/10.1093/eurjpc/zwab128
Khorana AA, Kuderer NM, Culakova E, et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008;111:4902-7.
DOI: https://doi.org/10.1182/blood-2007-10-116327
Carrier M, Abou-Nassar K, Mallick R, et al. Apixaban to Prevent Venous Thromboembolism in Patients with Cancer. N Engl J Med 2019;380:711-9.
DOI: https://doi.org/10.1056/NEJMoa1814468
Khorana AA, Soff GA, Kakkar AK, et al. Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer. N Engl J Med 2019;380:720-8.
DOI: https://doi.org/10.1056/NEJMoa1814630
How to Cite
Lun, R., & Siegal, D. M. (2024). Cancer-associated ischemic stroke: current knowledge and future directions. Bleeding, Thrombosis and Vascular Biology, 3(s1). https://doi.org/10.4081/btvb.2024.117
Copyright (c) 2024 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- Gary E. Raskob, Risk of recurrent venous thromboembolism in cancer patients after discontinuation of anticoagulant therapy , Bleeding, Thrombosis and Vascular Biology: Vol. 3 No. s1 (2024): 12th ICTHIC
- Benedetta Izzi, Simona Costanzo, Alessandro Gialluisi, Amalia De Curtis, Sara Magnacca, Teresa Panzera, Augusto Di Castelnuovo, Maria Benedetta Donati, Chiara Cerletti, Marc F. Hoylaerts, Giovanni de Gaetano, Licia Iacoviello, *on behalf of the Moli-sani Study Investigators, Platelet distribution width is associated with cardiovascular mortality in an adult general population , Bleeding, Thrombosis and Vascular Biology: Vol. 2 No. 3 (2023)
- Agnes Y.Y. Lee, Venous thromboembolism treatment in patients with cancer: reflections on an evolving landscape , Bleeding, Thrombosis and Vascular Biology: Vol. 3 No. s1 (2024): 12th ICTHIC
- Roberta Parisi, Simona Costanzo, Romy de Laat-Kremers, Augusto Di Castelnuovo, Amalia De Curtis, Teresa Panzera, Mariarosaria Persichillo, Chiara Cerletti, Giovanni de Gaetano, Maria Benedetta Donati, Licia Iacoviello, Bas de Laat , for the Moli-sani Study Investigators, Plasma fibrinogen levels and all-cause and cause-specific mortality in an Italian adult population: results from the Moli-sani study , Bleeding, Thrombosis and Vascular Biology: Vol. 2 No. 1 (2023)
- Marwa Eltemamy, Robert Namushi, Narayanamoorthi Saravanan, Importance of assessment of carotid plaques in the managementof acute ischemic stroke: floating intracarotid plaque , Bleeding, Thrombosis and Vascular Biology: Vol. 2 No. 3 (2023)
- Ang Li, Emily Zhou, Trends and updates on the epidemiology of cancer-associated thrombosis: a systematic review , Bleeding, Thrombosis and Vascular Biology: Vol. 3 No. s1 (2024): 12th ICTHIC
- Marcello Di Nisio, Matteo Candeloro, Nicola Potere, Ettore Porreca, Jeffrey I. Weitz, Factor XI inhibitors: a new option for the prevention and treatment of cancer-associated thrombosis , Bleeding, Thrombosis and Vascular Biology: Vol. 3 No. s1 (2024): 12th ICTHIC
- Francesco Marongiu, Elvira Grandone, Silvia Marongiu, Antonella Mameli, Doris Barcellona, Stroke in women: anticoagulation in a complicated puzzle , Bleeding, Thrombosis and Vascular Biology: Vol. 3 No. 2 (2024)
- Rosina Albisinni, Tommaso Marrazzo, Arta Karruli, Sabrina Manduca, Giuseppe Nobile, Nicola Galdieri, Marisa De Feo, Successful treatment of aortic arch mural thrombosis with low-dose, ultra-slow-flow thrombolysis: a case report and literature review , Bleeding, Thrombosis and Vascular Biology: Vol. 1 No. 3 (2022)
- Mehrie H. Patel, Alok A. Khorana, New drugs, old problems: immune checkpoint inhibitors and cancer-associated thrombosis , Bleeding, Thrombosis and Vascular Biology: Vol. 3 No. s1 (2024): 12th ICTHIC
You may also start an advanced similarity search for this article.
