{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T22:51:48Z","timestamp":1781823108825,"version":"3.54.5"},"reference-count":31,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background: Although thromboembolic complications are recognized in the treatment of acute lymphoblastic leukemia (ALL), ischemic strokes are rare but severe events. These life-threatening complications not only pose an immediate risk but can also result in long-term neurological deficits, significantly impacting a patient\u2019s quality of life. Identifying high-risk patients and implementing effective prophylaxis strategies are crucial for improving patient outcomes. In addition to strokes, these patients are also at risk of other embolic and thrombotic events, which can occur in up to 35% of patients. Despite this, there are still no clear guidelines for prophylactic management in pediatric patients treated for oncologic diseases. Results: Using the example of a 14-year-old male treated for ALL who suffered an ischemic stroke, we conducted a review of the literature on embolic and thrombotic events, neurological complications, methods of prevention, and ways to monitor and detect patients with an increased risk of such difficulties. We outlined our approach to the monitoring of prothrombotic factors, the interpretation of their levels, and the subsequent adjustment to prophylactic management based on these findings. As a result of this review, we reached two basic conclusions. First, thromboembolic episodes are not uncommon complications in pediatric patients and can cause long-lasting consequences, even after the cancer is cured. Secondly, despite such an urgent problem, clinicians are still struggling with the question of monitoring prothrombotic factors, the choice of drug, and the duration of prophylaxis. Their decisions depend on the experience of the treating center. Conclusions: The pediatric population being treated for malignant disease urgently requires the establishment of guidelines that standardize the management of thromboembolic events.<\/jats:p>","DOI":"10.3390\/jpm15060228","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T08:34:13Z","timestamp":1748853253000},"page":"228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Thromboembolic Risk and High Prothrombotic Factors in Childhood Acute Lymphoblastic Leukemia with Ischemic Stroke: A Literature Review of Personalized and Institutional Approaches to Prophylaxis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8641-4292","authenticated-orcid":false,"given":"Marta","family":"Malczewska","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology, Oncology, and Transplantology, University Hospital for Children, Antoniego G\u0119bali 6, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Dudkiewicz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, Oncology, and Transplantology, University Hospital for Children, Antoniego G\u0119bali 6, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7207-156X","authenticated-orcid":false,"given":"Joanna","family":"Zawitkowska","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, Oncology, and Transplantology, Medical University of Lublin, Antoniego G\u0119bali 6, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8760-0775","authenticated-orcid":false,"given":"Monika","family":"Lejman","sequence":"additional","affiliation":[{"name":"Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, Antoniego G\u0119bali 6, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.clml.2020.08.025","article-title":"Acute complications and survival analysis of childhood acute lymphoblastic leukemia: A 15-year experience","volume":"21","year":"2021","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1016\/S0140-6736(19)33018-1","article-title":"Acute lymphoblastic leukaemia","volume":"395","author":"Malard","year":"2020","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"49","DOI":"10.14744\/nci.2014.25744","article-title":"A thrombosis story and PRES","volume":"1","author":"Kartal","year":"2014","journal-title":"North. Clin. Istanb."},{"key":"ref_4","first-page":"93","article-title":"Impact of the mutation profile on thrombotic risk in cancer patients","volume":"222","author":"Lecumberri","year":"2022","journal-title":"Rev. Clin. Esp."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Rodriguez, V. (2022). Thrombosis complications in pediatric acute lymphoblastic leukemia: Risk factors, management, and prevention: Is there any role for pharmacologic prophylaxis?. Front. Pediatr., 10.","DOI":"10.3389\/fped.2022.828702"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"390","DOI":"10.29271\/jcpsp.2018.05.390","article-title":"Clinical spectrum and outcome of cerebral venous sinus thrombosis in children","volume":"28","author":"Javed","year":"2018","journal-title":"J. Coll. Physicians Surg. Pak."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e30425","DOI":"10.1002\/pbc.30425","article-title":"Central nervous system thrombosis in pediatric acute lymphoblastic leukemia in Turkey: A multicenter study","volume":"70","author":"Gelen","year":"2023","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1111\/jth.15699","article-title":"Venous thromboembolism in pediatric patients with acute lymphoblastic leukemia under chemotherapy treatment. Risk factors and usefulness of thromboprophylaxis. Results of LAL-SEHOP-PETHEMA-2013","volume":"20","author":"Gassiot","year":"2022","journal-title":"J. Thromb. Haemost."},{"key":"ref_9","unstructured":"Klukowska, A.H. (2025, March 10). Zmiany zakrzepowo-zatorowe u dzieci\u2013kazuistyka? Pediatria po Dyplomie 2023. Available online: https:\/\/podyplomie.pl\/pediatria\/39134%2Czmiany-zakrzepowo-zatorowe-u-dzieci-kazuistyka."},{"key":"ref_10","first-page":"53","article-title":"Genomic analysis of venous thrombosis in children with acute lymphoblastic leukemia from diverse ancestries","volume":"109","author":"Zheng","year":"2024","journal-title":"Haematologica"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Barzilai-Birenboim, S., Nirel, R., Arad-Cohen, N., Avrahami, G., Ben Harush, M., Barg, A.A., Bielorai, B., Elhasid, R., Gilad, G., and Toren, A. (2020). Venous thromboembolism and its risk factors in children with acute lymphoblastic leukemia in Israel: A population-based study. Cancers, 12.","DOI":"10.3390\/cancers12102759"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"129","DOI":"10.4137\/CMO.S18991","article-title":"Cancer-associated thrombosis: An overview","volume":"8","author":"Elyamany","year":"2014","journal-title":"Clin. Med. Insights Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1111\/jth.12075","article-title":"Coagulation and cancer: Biological and clinical aspects","volume":"11","author":"Marchetti","year":"2013","journal-title":"J. Thromb. Haemost."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Adramerina, A., and Economou, M. (2024). Thrombotic Complications in Pediatric Cancer. Children, 11.","DOI":"10.3390\/children11091096"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1097\/BPB.0000000000000053","article-title":"Risk factors for venous thromboembolism in hospitalized children and adolescents: A systemic review and pooled analysis","volume":"23","author":"Kim","year":"2014","journal-title":"J. Pediatr. Orthop. B"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1007\/s11739-019-02264-4","article-title":"Padua prediction score and IMPROVE score do predict in-hospital mortality in Internal Medicine patients","volume":"15","author":"Arpaia","year":"2020","journal-title":"Intern. Emerg. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1002\/ajh.26193","article-title":"Thrombosis is associated with worse survival in children with acute lymphoblastic leukemia: A report from CYP-C","volume":"96","author":"Kulkarni","year":"2021","journal-title":"Am. J. Hematol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1002\/rth2.12182","article-title":"Venous thromboembolism in a large cohort of children with acute lymphoblastic leukemia: Risk factors and effect on prognosis","volume":"3","author":"Klaassen","year":"2019","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"\u015aliwa-Tytko, P., Kaczmarska, A., Lejman, M., and Zawitkowska, J. (2022). Neurotoxicity associated with treatment of acute lymphoblastic leukemia chemotherapy and immunotherapy. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105515"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1097\/01.mph.0000157379.44167.b5","article-title":"Ischemic stroke in children treated for acute lymphoblastic leukemia: A retrospective study","volume":"27","author":"Santoro","year":"2005","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5277","DOI":"10.1200\/JCO.2006.07.2884","article-title":"Late-occurring stroke among long-term survivors of childhood leukemia and brain tumors: A report from the Childhood Cancer Survivor Study","volume":"24","author":"Bowers","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.pediatrneurol.2013.04.009","article-title":"Hemorrhagic and ischemic stroke in children with cancer","volume":"49","author":"Noje","year":"2013","journal-title":"Pediatr. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1111\/bjh.14231","article-title":"Cerebral sinovenous thrombosis in children and young adults with acute lymphoblastic leukaemia\u2014A cohort study from the United Kingdom","volume":"179","author":"Musgrave","year":"2017","journal-title":"Br. J. Haematol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Xie, L., Xu, Y., Zhou, G., Chen, F., Li, C., Ma, L., and Wen, F. (2024). Case Report: A successful outcome of nadroparin calcium therapy for cerebral venous sinus thrombosis in a child with acute lymphoblastic leukemia. Front. Pediatr., 12.","DOI":"10.3389\/fped.2024.1448445"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1177\/1076029615579098","article-title":"Biomarkers for prediction of central venous catheter-related thrombosis in patients with hematological malignancies","volume":"22","author":"Boersma","year":"2016","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1161\/ATVBAHA.109.190827","article-title":"High factor VIII levels independently predict venous thromboembolism in cancer patients: The cancer and thrombosis study","volume":"29","author":"Vormittag","year":"2009","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1159\/000496914","article-title":"Can biomarkers of coagulation, platelet activation, and inflammation predict venous thromboembolism in patients with haematological malignancies?","volume":"141","author":"Elmoamly","year":"2019","journal-title":"Acta Haematol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1182\/blood-2015-06-651539","article-title":"Improving evidence on anticoagulant therapies for venous thromboembolism in children: Key challenges and opportunities","volume":"126","author":"Goldenberg","year":"2015","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Klaassen, I.L.M., Lauw, M.N., van de Wetering, M.D., Biemond, B.J., Middeldorp, S., Abbink, F.C.H., Bierings, M., Te Loo, D.M.M.W., Pieters, R., and van der Sluis, I.M. (2017). TropicALL study: Thromboprophylaxis in children treated for acute lymphoblastic leukemia with low-molecular-weight heparin: A multicenter randomized controlled trial. BMC Pediatr., 17.","DOI":"10.1186\/s12887-017-0877-x"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.2217\/fon.15.114","article-title":"L-asparaginase and venous thromboembolism in acute lymphocytic leukemia","volume":"11","author":"Goyal","year":"2015","journal-title":"Future Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"756","DOI":"10.3324\/haematol.2018.194175","article-title":"THROMBOTECT\u2014A randomized study comparing low molecular weight heparin, antithrombin and unfractionated heparin for thromboprophylaxis during induction therapy of acute lymphoblastic leukemia in children and adolescents","volume":"104","author":"Greiner","year":"2019","journal-title":"Haematologica"}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/15\/6\/228\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:45:59Z","timestamp":1760031959000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/15\/6\/228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,2]]},"references-count":31,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["jpm15060228"],"URL":"https:\/\/doi.org\/10.3390\/jpm15060228","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,2]]}}}