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探索免疫检查点抑制剂与血栓形成之间新出现的关联。

Exploring the Emerging Association Between Immune Checkpoint Inhibitors and Thrombosis.

作者信息

Fawaz Hassan, Numan Hasan, El Charif Mohamad Hadi, Charbel Nicole, El Khoury Sacha, Rizkallah Joe, El Masri Amal, Tfayli Arafat, Kreidieh Firas

机构信息

Division of Hematology and Oncology, Department of Internal Medicine, American University of Beirut, Beirut P.O. Box 11-0236, Lebanon.

Department of Diagnostic Radiology, American University of Beirut, Beirut P.O. Box 11-0236, Lebanon.

出版信息

J Clin Med. 2025 May 15;14(10):3451. doi: 10.3390/jcm14103451.


DOI:10.3390/jcm14103451
PMID:40429445
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12112099/
Abstract

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.

摘要

免疫检查点抑制剂(ICIs)彻底改变了癌症治疗方式,但它们与血栓形成的关联带来了重大临床挑战。癌症患者本身就存在静脉血栓栓塞和动脉血栓形成的风险升高,化疗等治疗方式会进一步加剧这种风险。新出现的证据表明,ICIs 通过多因素机制导致血栓形成事件,包括免疫失调、T 细胞活化、内皮功能障碍、组织因子表达升高和纤维蛋白溶解受损。肥胖、吸烟、既往血栓形成事件和联合 ICI 治疗等其他风险因素会进一步增加血栓形成易感性。文献报道的 ICI 相关血栓形成的发病率各不相同,一些研究表明其风险与化疗相当,而另一些研究则强调发病率更高,尤其是在初始治疗阶段。治疗方法与癌症相关血栓形成的标准方案一致,使用低分子量肝素或直接口服抗凝剂,不过最佳治疗持续时间和预防性抗凝的作用仍需进一步研究。本综述全面概述了 ICI 相关血栓形成的机制、发病率和临床管理策略,强调了积极进行风险评估以优化患者治疗效果的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c795/12112099/983ec27db882/jcm-14-03451-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c795/12112099/983ec27db882/jcm-14-03451-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c795/12112099/983ec27db882/jcm-14-03451-g001.jpg

相似文献

[1]
Exploring the Emerging Association Between Immune Checkpoint Inhibitors and Thrombosis.

J Clin Med. 2025-5-15

[2]
Thromboembolic events associated with immune checkpoint inhibitors in cancer patients: A Bayesian network meta-analysis.

Thromb Res. 2025-2

[3]
Thrombotic Complications Associated with Immune Checkpoint Inhibitors.

Cancers (Basel). 2021-9-14

[4]
The Khorana score and venous and arterial thrombosis in patients with cancer treated with immune checkpoint inhibitors: A Danish cohort study.

J Thromb Haemost. 2022-12

[5]
Thrombotic risk of platinum combination chemotherapy with and without immune checkpoint inhibitors for advanced non-small cell lung cancer: a nationwide inpatient database study.

Cancer Immunol Immunother. 2023-11

[6]
Risk factors for cancer-associated thrombosis in patients undergoing treatment with immune checkpoint inhibitors.

Invest New Drugs. 2020-8

[7]
Interaction between NSCLC Cells, CD8 T-Cells and Immune Checkpoint Inhibitors Potentiates Coagulation and Promotes Metabolic Remodeling-New Cues on CAT-VTE.

Cells. 2024-2-7

[8]
Venous thrombotic events in patients treated with immune checkpoint inhibitors for non-small cell lung cancer: A retrospective multicentric cohort study.

Thromb Res. 2021-9

[9]
Evaluation of direct oral anticoagulants for the treatment of cancer-associated thrombosis: an update.

J Thromb Thrombolysis. 2019-4

[10]
Incidence of thromboembolism in patients with melanoma on immune checkpoint inhibitor therapy and its adverse association with survival.

J Immunother Cancer. 2021-1

本文引用的文献

[1]
Influence of the Immune Checkpoint Inhibitors on the Hemostatic Potential of Blood Plasma.

Transfus Med Hemother. 2024-8-21

[2]
Tissue factor-dependent colitogenic CD4 T cell thrombogenicity is regulated by activated protein C signalling.

Nat Commun. 2025-2-16

[3]
Early Change in C-Reactive Protein and Venous Thromboembolism in Patients Treated With Immune Checkpoint Inhibitors.

JACC CardioOncol. 2024-11-12

[4]
Thromboembolic events associated with immune checkpoint inhibitors in cancer patients: A Bayesian network meta-analysis.

Thromb Res. 2025-2

[5]
The role of artificial intelligence in immune checkpoint inhibitor research: A bibliometric analysis.

Hum Vaccin Immunother. 2024-12-31

[6]
Targeted modulation of myeloid-derived suppressor cells in the tumor microenvironment: Implications for cancer therapy.

Biomed Pharmacother. 2024-11

[7]
Validation of risk assessment scores in predicting venous thromboembolism in patients with lung cancer receiving immune checkpoint inhibitors.

BMC Pulm Med. 2024-10-10

[8]
Thromboembolism during immune checkpoint inhibitor therapy: frequency and risk factors.

Discov Oncol. 2024-10-5

[9]
Predictive Biomarkers and Resistance Mechanisms of Checkpoint Inhibitors in Malignant Solid Tumors.

Int J Mol Sci. 2024-9-6

[10]
Prognostic Significance of Plasma Neutrophil Extracellular Trap Levels in Patients with Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors.

Biomedicines. 2024-8-12

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