{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:50:57Z","timestamp":1787028657335,"version":"build-2736575974"},"reference-count":123,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but their association with thrombosis presents significant clinical challenges. Patients with cancer already exhibit elevated risks for venous thromboembolism and arterial thrombosis, with treatment modalities like chemotherapy further exacerbating this risk. Emerging evidence suggests that ICIs contribute to thrombotic events through multifactorial mechanisms, including immune dysregulation, T cell activation, endothelial dysfunction, elevated tissue factor expression, and impaired fibrinolysis. Additional risk factors such as obesity, smoking, prior thrombotic events, and combination ICI therapy further increase thrombosis susceptibility. The literature reports varying incidence rates of ICI-associated thrombosis, with some studies indicating comparable risks to chemotherapy, while others highlight higher rates, particularly during the initial treatment phase. Management aligns with standard protocols for cancer-associated thrombosis, using low-molecular-weight heparin or direct oral anticoagulants, though optimal treatment duration and the role of prophylactic anticoagulation require further investigation. This review provides a comprehensive overview of the mechanisms, incidence rates, and clinical management strategies of ICI-associated thrombosis, emphasizing the importance of proactive risk assessment to optimize patient outcomes.<\/jats:p>","DOI":"10.3390\/jcm14103451","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T06:10:44Z","timestamp":1747289444000},"page":"3451","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Exploring the Emerging Association Between Immune Checkpoint Inhibitors and Thrombosis"],"prefix":"10.3390","volume":"14","author":[{"given":"Hassan","family":"Fawaz","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, American University of Beirut, Beirut P.O. 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Haemost."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1182\/blood.2020007338","article-title":"Venous thromboembolism in cancer patients: A population-based cohort study","volume":"137","author":"Mulder","year":"2021","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.jacc.2017.06.047","article-title":"Risk of Arterial Thromboembolism in Patients With Cancer","volume":"70","author":"Navi","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1002\/ajh.25494","article-title":"Bleeding incidence and risk factors among cancer patients treated with anticoagulation","volume":"94","author":"Angelini","year":"2019","journal-title":"Am. J. Hematol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1182\/blood.2024025362","article-title":"Bleeding events in patients with cancer: Incidence, risk factors, and impact on prognosis in a prospective cohort study","volume":"144","author":"Englisch","year":"2024","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1182\/blood-2024-206168","article-title":"Elimination of Modifiable Risk Factors for Anticoagulant-Related Bleeding in Patients with Cancer Reduces the Probability of Bleeding","volume":"144","author":"Sanfilippo","year":"2024","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1126\/science.aaa8172","article-title":"The future of immune checkpoint therapy","volume":"348","author":"Sharma","year":"2015","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Wang, T.-F., Khorana, A.A., and Carrier, M. (2021). Thrombotic Complications Associated with Immune Checkpoint Inhibitors. Cancers, 13.","DOI":"10.3390\/cancers13184606"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1136\/bmj.325.7369.887","article-title":"Venous thromboembolism: Pathophysiology, clinical features, and prevention","volume":"325","author":"Turpie","year":"2002","journal-title":"BMJ"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S276","DOI":"10.21037\/cdt.2017.09.01","article-title":"Deep vein thrombosis: Pathogenesis, diagnosis, and medical management","volume":"7","author":"Stone","year":"2017","journal-title":"Cardiovasc. Diagn. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1093\/annonc\/mdp068","article-title":"Cancer and thrombosis: Implications of published guidelines for clinical practice","volume":"20","author":"Khorana","year":"2009","journal-title":"Ann. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"101220","DOI":"10.1016\/j.blre.2024.101220","article-title":"Thrombotic events associated with immune checkpoint inhibitors and novel antithrombotic strategies to mitigate bleeding risk","volume":"67","author":"Chen","year":"2024","journal-title":"Blood Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1136\/thoraxjnl-2021-217260","article-title":"Infections due to dysregulated immunity: An emerging complication of cancer immunotherapy","volume":"77","author":"Morelli","year":"2022","journal-title":"Thorax"},{"key":"ref_15","first-page":"171","article-title":"Autoimmune diseases and venous thromboembolism: A review of the literature","volume":"2","author":"Li","year":"2012","journal-title":"Am. J. Cardiovasc. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1158\/2326-6066.CIR-18-0245","article-title":"Autoantibody Development under Treatment with Immune-Checkpoint Inhibitors","volume":"7","author":"Rozeman","year":"2019","journal-title":"Cancer Immunol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2528","DOI":"10.1200\/JCO.2022.40.16_suppl.2528","article-title":"Customized autoantibodies (autoAbs) profiling to predict and monitor immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICI)","volume":"40","author":"Genta","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S1396","DOI":"10.1016\/j.annonc.2023.09.156","article-title":"MO2-7 A multicenter prospective observational study of pre-existing autoantibodies in patients with small-cell lung cancer treated with ICI","volume":"34","author":"Hata","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cellimm.2016.09.009","article-title":"PD-1\/PD-L and autoimmunity: A growing relationship","volume":"310","author":"Zamani","year":"2016","journal-title":"Cell. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.rdc.2024.01.001","article-title":"Pre-existing Autoimmune Diseases and Immune Checkpoint Inhibitors for Cancer Treatment: Considerations About Initiation, Flares, Immune-Related Adverse Events, and Cancer Progression","volume":"50","author":"Sparks","year":"2024","journal-title":"Rheum. Dis. Clin. N. Am."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6341","DOI":"10.1007\/s00432-023-04582-9","article-title":"Immune-related adverse events after immune checkpoint inhibitor exposure in adult cancer patients with pre-existing autoimmune diseases","volume":"149","author":"Shatila","year":"2023","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"114148","DOI":"10.1016\/j.ejca.2024.114148","article-title":"A systematic review and meta-analysis of observational studies and uncontrolled trials reporting on the use of checkpoint blockers in patients with cancer and pre-existing autoimmune disease","volume":"207","author":"Kachira","year":"2024","journal-title":"Eur. J. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1002\/art.41068","article-title":"Safety and Efficacy of Immune Checkpoint Inhibitors in Patients With Cancer and Preexisting Autoimmune Disease: A Nationwide, Multicenter Cohort Study","volume":"71","author":"Tison","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sagrero-Fabela, N., Ch\u00e1vez-Mireles, R., Salazar-Camarena, D.C., and Palafox-S\u00e1nchez, C.A. (2024). Exploring the Role of PD-1 in the Autoimmune Response: Insights into Its Implication in Systemic Lupus Erythematosus. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202406.1533.v1"},{"key":"ref_25","first-page":"425","article-title":"A case of catastrophic antiphospholipid syndrome during nivolumab treatment for gastric cancer","volume":"8","author":"Miyakoshi","year":"2019","journal-title":"Ann. Jpn. Respir. Soc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2050313x20972225","DOI":"10.1177\/2050313X20972225","article-title":"Severe mesenteric ischemia with multiple organ failure in a patient previously treated with a humanized monoclonal antibody against programmed death receptor-1 (pembrolizumab), a case of pembrolizumab associated catastrophic antiphospholipid syndrome?","volume":"8","author":"Vos","year":"2020","journal-title":"SAGE Open Med. Case Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2974","DOI":"10.1172\/JCI31344","article-title":"Proatherogenic immune responses are regulated by the PD-1\/PD-L pathway in mice","volume":"117","author":"Gotsman","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1161\/ATVBAHA.111.224709","article-title":"Impairment of the programmed cell death-1 pathway increases atherosclerotic lesion development and inflammation","volume":"31","author":"Bu","year":"2011","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Cochain, C., Chaudhari, S.M., Koch, M., Wiendl, H., Eckstein, H.H., and Zernecke, A. (2014). Programmed cell death-1 deficiency exacerbates T cell activation and atherogenesis despite expansion of regulatory T cells in atherosclerosis-prone mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093280"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/j.1600-065X.2010.00923.x","article-title":"The PD-1 pathway in tolerance and autoimmunity","volume":"236","author":"Francisco","year":"2010","journal-title":"Immunol. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Grievink, H.W., Smit, V., Verwilligen, R.A.F., Bernab\u00e9 Kleijn, M.N.A., Smeets, D., Binder, C.J., Yagita, H., Moerland, M., Kuiper, J., and Bot, I. (2021). Stimulation of the PD-1 Pathway Decreases Atherosclerotic Lesion Development in Ldlr Deficient Mice. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.740531"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wilhelm, G., Mertowska, P., Mertowski, S., Przysucha, A., Stru\u017cyna, J., Grywalska, E., and Torres, K. (2023). The Crossroads of the Coagulation System and the Immune System: Interactions and Connections. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241612563"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1182\/blood-2023-184570","article-title":"Immune Checkpoint Blockade Promotes Thrombosis Via T-Cell and Neutrophil Activation, and Tumor-Cell Associated Tissue Factor (TF) in a Murine Model of Colorectal Cancer","volume":"142","author":"Shim","year":"2023","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Sato, R., Imamura, K., Sakata, S., Ikeda, T., Horio, Y., Iyama, S., Akaike, K., Hamada, S., Jodai, T., and Nakashima, K. (2019). Disorder of Coagulation-Fibrinolysis System: An Emerging Toxicity of Anti-PD-1\/PD-L1 Monoclonal Antibodies. J. Clin. Med., 8.","DOI":"10.3390\/jcm8060762"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1038\/s41467-025-57001-7","article-title":"Tissue factor-dependent colitogenic CD4+ T cell thrombogenicity is regulated by activated protein C signalling","volume":"16","author":"Leon","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Tormoen, G.W., Rugonyi, S., Gruber, A., and McCarty, O.J. (2011). The role of carrier number on the procoagulant activity of tissue factor in blood and plasma. Phys. Biol., 8.","DOI":"10.1088\/1478-3975\/8\/6\/066005"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"M\u00f6ller, M., Orth, V., Umansky, V., Hetjens, S., Braun, V., Rei\u00dffelder, C., Hardt, J., and Seyfried, S. (2024). Myeloid-derived suppressor cells in peripheral blood as predictive biomarkers in patients with solid tumors undergoing immune checkpoint therapy: Systematic review and meta-analysis. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1403771"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1007\/s12272-019-01165-6","article-title":"Role of myeloid-derived suppressor cells in immune checkpoint inhibitor therapy in cancer","volume":"42","author":"Park","year":"2019","journal-title":"Arch. Pharm. Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Olivares-Hern\u00e1ndez, A., Figuero-P\u00e9rez, L., Ter\u00e1n-Brage, E., L\u00f3pez-Guti\u00e9rrez, \u00c1., Velasco, \u00c1.T., Sarmiento, R.G., Cruz-Hern\u00e1ndez, J.J., and Miramontes-Gonz\u00e1lez, J.P. (2021). Resistance to Immune Checkpoint Inhibitors Secondary to Myeloid-Derived Suppressor Cells: A New Therapeutic Targeting of Haematological Malignancies. J. Clin. Med., 10.","DOI":"10.3390\/jcm10091919"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e170762","DOI":"10.1172\/JCI170762","article-title":"Enhancing immunotherapy response in melanoma: Myeloid-derived suppressor cells as a therapeutic target","volume":"133","author":"Lasser","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Qi, Y., Zhang, L., Liu, Y., Li, Y., Liu, Y., and Zhang, Z. (2024). Targeted modulation of myeloid-derived suppressor cells in the tumor microenvironment: Implications for cancer therapy. Biomed. Pharmacother., 180.","DOI":"10.1016\/j.biopha.2024.117590"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Rolling, C., Regenhardt, J., Lehr, C., Beckmann, L., Bokemeyer, C., and Langer, F. (March, January 27). Immune checkpoints are upregulated on activated platelets and monocytes. Proceedings of the GTH Congress 2024\u201468th Annual Meeting of the Society of Thrombosis and Haemostasis Research\u2014Building Bridges in Coagulation, Vienna, Austria.","DOI":"10.1055\/s-0044-1779098"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Hou, A., Hou, K., Huang, Q., Lei, Y., and Chen, W. (2020). Targeting Myeloid-Derived Suppressor Cell, a Promising Strategy to Overcome Resistance to Immune Checkpoint Inhibitors. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00783"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.medj.2021.02.002","article-title":"Increased Incidence of Venous Thromboembolism with Cancer Immunotherapy","volume":"2","author":"Roopkumar","year":"2021","journal-title":"Med"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1007\/s12094-022-02860-5","article-title":"Immune checkpoint inhibitors-associated thrombosis in patients with lung cancer and melanoma: A study of the Spanish society of medical oncology (SEOM) thrombosis and cancer group","volume":"24","author":"Garay","year":"2022","journal-title":"Clin. Transl. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Charpidou, A., Gerotziafas, G., Popat, S., Araujo, A., Scherpereel, A., Kopp, H.G., Bironzo, P., Massard, G., Jim\u00e9nez, D., and Falanga, A. (2024). Lung Cancer Related Thrombosis (LCART): Focus on Immune Checkpoint Blockade. Cancers, 16.","DOI":"10.3390\/cancers16020450"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/ejh.13734","article-title":"Assessing the risk of thromboembolism in cancer patients receiving immunotherapy","volume":"108","author":"Goel","year":"2022","journal-title":"Eur. J. Haematol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"S51","DOI":"10.1016\/j.thromres.2022.01.006","article-title":"Old is new again: Emergence of thromboembolic complications in cancer patients on immunotherapy","volume":"213","author":"McCrae","year":"2022","journal-title":"Thromb. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.healun.2019.02.009","article-title":"Prothrombotic activity of cytokine-activated endothelial cells and shear-activated platelets in the setting of ventricular assist device support","volume":"38","author":"Apostoli","year":"2019","journal-title":"J. Heart Lung Transpl."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Horaguchi, S., Nakahara, Y., Igarashi, Y., Kouro, T., Wei, F., Murotani, K., Udagawa, S., Higashijima, N., Matsuo, N., and Murakami, S. (2024). Prognostic Significance of Plasma Neutrophil Extracellular Trap Levels in Patients with Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors. Biomedicines, 12.","DOI":"10.3390\/biomedicines12081831"},{"key":"ref_51","first-page":"120","article-title":"Influence of the Immune Checkpoint Inhibitors on the Hemostatic Potential of Blood Plasma","volume":"52","author":"Patalakh","year":"2024","journal-title":"Transfus. Med. Hemother."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Ibrahim, A.A., Fujimura, T., Uno, T., Terada, T., Hirano, K.I., Hosokawa, H., Ohta, A., Miyata, T., Ando, K., and Yahata, T. (2024). Plasminogen activator inhibitor-1 promotes immune evasion in tumors by facilitating the expression of programmed cell death-ligand 1. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1365894"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s00395-024-01068-8","article-title":"Molecular fingerprints of cardiovascular toxicities of immune checkpoint inhibitors","volume":"120","author":"Gergely","year":"2024","journal-title":"Basic Res. Cardiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s11912-020-00925-8","article-title":"New Insights into Mechanisms of Immune Checkpoint Inhibitor-Induced Cardiovascular Toxicity","volume":"22","author":"Khunger","year":"2020","journal-title":"Curr. Oncol. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Rubio-Infante, N., Ram\u00edrez-Flores, Y.A., Castillo, E.C., Lozano, O., Garc\u00eda-Rivas, G., and Torre-Amione, G. (2022). A Systematic Review of the Mechanisms Involved in Immune Checkpoint Inhibitors Cardiotoxicity and Challenges to Improve Clinical Safety. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.851032"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e14610","DOI":"10.1200\/JCO.2024.42.16_suppl.e14610","article-title":"Risk factors for thrombotic events among patients taking immune checkpoint inhibitors: A systematic review and meta-analysis","volume":"42","author":"Song","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"S689","DOI":"10.1016\/j.annonc.2023.09.2288","article-title":"1154P Thromboembolic events in patients with melanoma receiving immune checkpoint inhibitors: Incidence and risk factors","volume":"34","author":"Hofman","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.1182\/blood-2023-187867","article-title":"Risks for Venous Thromboembolism with Immune Checkpoint Inhibitor Therapy","volume":"142","author":"Connors","year":"2023","journal-title":"Blood"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3032","DOI":"10.3390\/curroncol30030230","article-title":"Immune Checkpoint Inhibitors-Associated Thrombosis: Incidence, Risk Factors and Management","volume":"30","author":"Wang","year":"2023","journal-title":"Curr. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ejca.2021.09.010","article-title":"Immune checkpoint inhibitors for cancer and venous thromboembolic events","volume":"158","author":"Gong","year":"2021","journal-title":"Eur. J. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s12672-024-01416-z","article-title":"Thromboembolism during immune checkpoint inhibitor therapy: Frequency and risk factors","volume":"15","author":"Ide","year":"2024","journal-title":"Discov. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1055\/s-0043-1769609","article-title":"Risk Factors of Venous Thromboembolic Disease in Cancer Patients Treated with Immune Checkpoint Inhibitor","volume":"123","author":"Bordenave","year":"2023","journal-title":"Thromb. Haemost."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"18531","DOI":"10.1002\/cam4.6455","article-title":"Association of immune checkpoint inhibitors therapy with arterial thromboembolic events in cancer patients: A retrospective cohort study","volume":"12","author":"Zhu","year":"2023","journal-title":"Cancer Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1080\/17474086.2023.2276209","article-title":"Evaluating the effect of immune checkpoint inhibitors on venous thromboembolism in non-small cell lung cancer patients","volume":"16","author":"He","year":"2023","journal-title":"Expert Rev. Hematol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1016\/j.jsps.2022.06.010","article-title":"Immune checkpoint inhibitors and potential risk of thromboembolic events: Analysis of the WHO global database of individual case safety reports","volume":"30","author":"Alghamdi","year":"2022","journal-title":"Saudi Pharm. J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1002\/ajh.26954","article-title":"Venous thromboembolism risk in cancer patients receiving first-line immune checkpoint inhibitor versus chemotherapy","volume":"98","author":"Li","year":"2023","journal-title":"Am. J. Hematol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s12094-024-03570-w","article-title":"Immune checkpoint inhibitors-associated thrombosis in patients with head and neck cancer: A study of the Spanish society of medical oncology (SEOM) thrombosis and cancer group","volume":"27","author":"Adoamnei","year":"2024","journal-title":"Clin. Transl. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1161\/CIRCULATIONAHA.120.049981","article-title":"Association Between Immune Checkpoint Inhibitors with Cardiovascular Events and Atherosclerotic Plaque","volume":"142","author":"Drobni","year":"2020","journal-title":"Circulation"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1182\/bloodadvances.2020003442","article-title":"American Society of Hematology 2021 guidelines for management of venous thromboembolism: Prevention and treatment in patients with cancer","volume":"5","author":"Lyman","year":"2021","journal-title":"Blood Adv."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5434","DOI":"10.3390\/curroncol28060453","article-title":"Treatment Algorithm in Cancer-Associated Thrombosis: Updated Canadian Expert Consensus","volume":"28","author":"Carrier","year":"2021","journal-title":"Curr. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Lee, A.Y., Bauersachs, R., Janas, M.S., Jarner, M.F., Kamphuisen, P.W., Meyer, G., and Khorana, A.A. (2013). CATCH: A randomised clinical trial comparing long-term tinzaparin versus warfarin for treatment of acute venous thromboembolism in cancer patients. BMC Cancer, 13.","DOI":"10.1186\/1471-2407-13-284"},{"key":"ref_72","first-page":"CD006650","article-title":"Anticoagulation for the long-term treatment of venous thromboembolism in people with cancer","volume":"6","author":"Kahale","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(11)61753-4","article-title":"Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): A randomised controlled trial","volume":"379","author":"Enden","year":"2012","journal-title":"Lancet"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1056\/NEJMoa1711948","article-title":"Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism","volume":"378","author":"Raskob","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1200\/JCO.2018.78.8034","article-title":"Comparison of an Oral Factor Xa Inhibitor with Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D)","volume":"36","author":"Young","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1200\/JCO.23.00294","article-title":"Venous Thromboembolism Prophylaxis and Treatment in Patients with Cancer: ASCO Guideline Update","volume":"41","author":"Key","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1161\/CIRCULATIONAHA.114.008828","article-title":"Aspirin for the Prevention of Recurrent Venous Thromboembolism","volume":"130","author":"Simes","year":"2014","journal-title":"Circulation"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"f5133","DOI":"10.1136\/bmj.f5133","article-title":"Efficacy and safety outcomes of oral anticoagulants and antiplatelet drugs in the secondary prevention of venous thromboembolism: Systematic review and network meta-analysis","volume":"347","author":"Castellucci","year":"2013","journal-title":"BMJ Br. Med. J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1016\/j.jacc.2017.08.037","article-title":"Antiplatelet Agents for the Treatment and Prevention of Coronary Atherothrombosis","volume":"70","author":"Patrono","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"100619","DOI":"10.1016\/j.blre.2019.100619","article-title":"Management of bleeding and procedures in patients on antiplatelet therapy","volume":"39","author":"Swan","year":"2020","journal-title":"Blood Rev."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1080\/14740338.2019.1680637","article-title":"Bleeding after antiplatelet therapy for the treatment of acute coronary syndromes: A review of the evidence and evolving paradigms","volume":"18","author":"Buccheri","year":"2019","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.jacc.2014.03.049","article-title":"Aspirin Therapy in Primary Cardiovascular Disease Prevention: A Position Paper of the European Society of Cardiology Working Group on Thrombosis","volume":"64","author":"Halvorsen","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1056\/NEJMoa1804988","article-title":"Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus","volume":"379","author":"Bowman","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1161\/CIRCULATIONAHA.112.000799","article-title":"Integrin \u03b16\u03b21 Is the Main Receptor for Vascular Laminins and Plays a Role in Platelet Adhesion, Activation, and Arterial Thrombosis","volume":"128","author":"Schaff","year":"2013","journal-title":"Circulation"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1182\/blood-2012-08-449694","article-title":"Delayed targeting of CD39 to activated platelet GPIIb\/IIIa via a single-chain antibody: Breaking the link between antithrombotic potency and bleeding?","volume":"121","author":"Hohmann","year":"2013","journal-title":"Blood"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e072715","DOI":"10.1136\/bmj-2022-072715","article-title":"Prevention of venous thromboembolism in patients with cancer","volume":"381","author":"Guntupalli","year":"2023","journal-title":"BMJ"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ejim.2023.11.017","article-title":"Event rates and risk factors for venous thromboembolism and major bleeding in a population of hospitalized adult patients with acute medical illness receiving enoxaparin thromboprophylaxis","volume":"121","author":"Agnelli","year":"2024","journal-title":"Eur. J. Intern. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.amjmed.2013.09.015","article-title":"Lack of evidence to support thromboprophylaxis in hospitalized medical patients with cancer","volume":"127","author":"Carrier","year":"2014","journal-title":"Am. J. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.annonc.2022.12.014","article-title":"Venous thromboembolism in cancer patients: ESMO Clinical Practice Guideline","volume":"34","author":"Falanga","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3285","DOI":"10.1182\/blood-2017-03-742304","article-title":"How I treat recurrent venous thromboembolism in patients receiving anticoagulant therapy","volume":"129","author":"Schulman","year":"2017","journal-title":"Blood"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"10760296241232864","DOI":"10.1177\/10760296241232864","article-title":"The Contribution of Inherited Thrombophilia to Venous Thromboembolism in Cancer Patients","volume":"30","author":"Costa","year":"2024","journal-title":"Clin. Appl. Thromb.\/Hemost."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Dicks, A.B., Moussallem, E., Stanbro, M., Walls, J., Gandhi, S., and Gray, B.H. (2024). A Comprehensive Review of Risk Factors and Thrombophilia Evaluation in Venous Thromboembolism. J. Clin. Med., 13.","DOI":"10.3390\/jcm13020362"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1002\/ajh.27222","article-title":"Inherited thrombophilia gene mutations and risk of venous thromboembolism in patients with cancer: A systematic review and meta-analysis","volume":"99","author":"Roy","year":"2024","journal-title":"Am. J. Hematol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1182\/bloodadvances.2021006484","article-title":"Validation of the Khorana score for predicting venous thromboembolism in 40 218 patients with cancer initiating chemotherapy","volume":"6","author":"Overvad","year":"2022","journal-title":"Blood Adv."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1002\/ajh.25603","article-title":"Predicting venous thromboembolism in multiple myeloma: Development and validation of the IMPEDE VTE score","volume":"94","author":"Sanfilippo","year":"2019","journal-title":"Am. J. Hematol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1111\/bjh.18630","article-title":"External validation of the SAVED score for venous thromboembolism risk stratification in patients with multiple myeloma receiving immunomodulatory drugs","volume":"201","author":"Dima","year":"2023","journal-title":"Br. J. Haematol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Zhang, J., Xie, Y., Yang, L., Yang, M., Xu, R., and Liu, D. (2024). Validation of risk assessment scores in predicting venous thromboembolism in patients with lung cancer receiving immune checkpoint inhibitors. BMC Pulm. Med., 24.","DOI":"10.1186\/s12890-024-03323-z"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2926","DOI":"10.1200\/JCO.22.01542","article-title":"Derivation and Validation of a Clinical Risk Assessment Model for Cancer-Associated Thrombosis in Two Unique US Health Care Systems","volume":"41","author":"Li","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3214","DOI":"10.1182\/bloodadvances.2024013166","article-title":"Converting IMPROVE bleeding and VTE risk assessment models into a fast-and-frugal decision tree for optimal hospital VTE prophylaxis","volume":"8","author":"Djulbegovic","year":"2024","journal-title":"Blood Adv."},{"key":"ref_100","first-page":"1183","article-title":"IMPROVE bleeding score predicts major bleeding in advanced gastrointestinal cancer patients with venous thromboembolism","volume":"52","author":"Kusaba","year":"2022","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2881","DOI":"10.1200\/JCO.23.00100","article-title":"Fine Tuning Venous Thromboembolism Risk Prediction in Patients with Cancer","volume":"41","author":"Connors","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1111\/jth.15883","article-title":"The Khorana score and venous and arterial thrombosis in patients with cancer treated with immune checkpoint inhibitors: A Danish cohort study","volume":"20","author":"Overvad","year":"2022","journal-title":"J. Thromb. Haemost."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1161\/CIRCULATIONAHA.121.057847","article-title":"Association of Bleeding Severity with Mortality in Extended Thromboprophylaxis of Medically Ill Patients in the MAGELLAN and MARINER Trials","volume":"145","author":"Spyropoulos","year":"2022","journal-title":"Circulation"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1200\/JCO.19.01461","article-title":"Venous Thromboembolism Prophylaxis and Treatment in Patients with Cancer: ASCO Clinical Practice Guideline Update","volume":"38","author":"Key","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"278","DOI":"10.7326\/0003-4819-146-4-200702200-00007","article-title":"Meta-analysis: Anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients","volume":"146","author":"Dentali","year":"2007","journal-title":"Ann. Intern. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1182\/bloodadvances.2019000840","article-title":"DOACs vs LMWHs in hospitalized medical patients: A systematic review and meta-analysis that informed 2018 ASH guidelines","volume":"4","author":"Neumann","year":"2020","journal-title":"Blood Adv."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa1814468","article-title":"Apixaban to Prevent Venous Thromboembolism in Patients with Cancer","volume":"380","author":"Carrier","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1056\/NEJMoa1814630","article-title":"Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer","volume":"380","author":"Khorana","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"S106","DOI":"10.1016\/S0049-3848(20)30406-0","article-title":"Coagulation signaling and cancer immunotherapy","volume":"191","author":"Ruf","year":"2020","journal-title":"Thromb. Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"eaaw8405","DOI":"10.1126\/sciimmunol.aaw8405","article-title":"Myeloid cell\u2013synthesized coagulation factor X dampens antitumor immunity","volume":"4","author":"Graf","year":"2019","journal-title":"Sci. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1111\/j.1538-7836.2012.04874.x","article-title":"Extended thromboprophylaxis for medically ill patients with decreased mobility: Does it improve outcomes?","volume":"10","author":"Sharma","year":"2012","journal-title":"J. Thromb. Haemost."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.jaccao.2024.09.007","article-title":"Early Change in C-Reactive Protein and Venous Thromboembolism in Patients Treated With Immune Checkpoint Inhibitors","volume":"6","author":"Moik","year":"2024","journal-title":"JACC CardioOncol."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Wang, J., Ma, Y., Lin, H., Wang, J., and Cao, B. (2024). Predictive biomarkers for immune-related adverse events in cancer patients treated with immune-checkpoint inhibitors. BMC Immunol., 25.","DOI":"10.1186\/s12865-024-00599-y"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"eadj0785","DOI":"10.1126\/sciadv.adj0785","article-title":"Cell-cell communication network-based interpretable machine learning predicts cancer patient response to immune checkpoint inhibitors","volume":"10","author":"Lee","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2429893","DOI":"10.1080\/21645515.2024.2429893","article-title":"The role of artificial intelligence in immune checkpoint inhibitor research: A bibliometric analysis","volume":"20","author":"Zhao","year":"2024","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Bai, R., Lv, Z., Xu, D., and Cui, J. (2020). Predictive biomarkers for cancer immunotherapy with immune checkpoint inhibitors. Biomark. Res., 8.","DOI":"10.1186\/s40364-020-00209-0"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Pavelescu, L.A., Enache, R.M., Ro\u015fu, O.A., Profir, M., Cre\u0163oiu, S.M., and Gaspar, B.S. (2024). Predictive Biomarkers and Resistance Mechanisms of Checkpoint Inhibitors in Malignant Solid Tumors. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25179659"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e542","DOI":"10.1016\/S1470-2045(16)30406-5","article-title":"Predictive biomarkers for checkpoint inhibitor-based immunotherapy","volume":"17","author":"Gibney","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"109243","DOI":"10.1016\/j.thromres.2024.109243","article-title":"Thromboembolic events associated with immune checkpoint inhibitors in cancer patients: A Bayesian network meta-analysis","volume":"246","author":"Lin","year":"2025","journal-title":"Thromb. Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"10760296231206799","DOI":"10.1177\/10760296231206799","article-title":"Associations Between Immune-Related Venous Thromboembolism and Efficacy of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis","volume":"29","author":"Li","year":"2023","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_121","first-page":"e2300060","article-title":"Prediction of Venous Thromboembolism in Patients with Cancer Using Machine Learning Approaches: A Systematic Review and Meta-Analysis","volume":"7","year":"2023","journal-title":"JCO Clin. Cancer Inf."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Mantha, S., Chatterjee, S., Singh, R., Cadley, J., Poon, C., Chatterjee, A., Kelly, D., Sterpi, M., Soff, G., and Zwicker, J. (2023). Application of Machine Learning to the Prediction of Cancer-Associated Venous Thromboembolism. Res. Sq., in press.","DOI":"10.21203\/rs.3.rs-2870367\/v1"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Zhou, X., Ni, Y., Liang, X., Lin, Y., An, B., He, X., and Zhao, X. (2022). Mechanisms of tumor resistance to immune checkpoint blockade and combination strategies to overcome resistance. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.915094"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/10\/3451\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:33:01Z","timestamp":1760031181000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/10\/3451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,15]]},"references-count":123,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["jcm14103451"],"URL":"https:\/\/doi.org\/10.3390\/jcm14103451","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,15]]}}}