Hisada Y, Geddings J E, Ay C, Mackman N
Division of Hematology and Oncology, Department of Medicine, Thrombosis and Hemostasis Program, UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
K.G. Jensen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway.
J Thromb Haemost. 2015 Aug;13(8):1372-82. doi: 10.1111/jth.13009. Epub 2015 Jun 26.
Cancer patients have a ~4 fold increased risk of venous thromboembolism (VTE) compared with the general population and this is associated with significant morbidity and mortality. This review summarizes our current knowledge of VTE and cancer, from mouse models to clinical studies. Notably, the risk of VTE varies depending on the type and stage of cancer. For instance, pancreatic and brain cancer patients have a higher risk of VTE than breast and prostate cancer patients. Moreover, patients with metastatic disease have a higher risk than those with localized tumors. Tumor-derived procoagulant factors and growth factors may directly and indirectly enhance VTE. For example, increased levels of circulating tumor-derived, tissue factor-positive microvesicles may trigger VTE. In a mouse model of ovarian cancer, tumor-derived IL-6 and hepatic thrombopoietin have been linked to increased platelet production and thrombosis. In addition, mouse models of mammary and lung cancer showed that tumor-derived granulocyte colony-stimulating factor causes neutrophilia and activation of neutrophils. Activated neutrophils can release neutrophil extracellular traps (NETs) that enhance thrombosis. Cell-free DNA in the blood derived from cancer cells, NETs and treatment with cytotoxic drugs can activate the clotting cascade. These studies suggest that there are multiple mechanisms for VTE in patients with different types of cancer. Preventing and treating VTE in cancer patients is challenging; the current recommendations are to use low-molecular-weight heparin. Understanding the underlying mechanisms may allow the development of new therapies to safely prevent VTE in cancer patients.
与普通人群相比，癌症患者发生静脉血栓栓塞（VTE）的风险增加约4倍，这与显著的发病率和死亡率相关。本综述总结了我们目前对VTE与癌症的认识，涵盖从小鼠模型到临床研究。值得注意的是，VTE的风险因癌症类型和分期而异。例如，胰腺癌和脑癌患者发生VTE的风险高于乳腺癌和前列腺癌患者。此外，转移性疾病患者的风险高于局限性肿瘤患者。肿瘤衍生的促凝因子和生长因子可能直接或间接增加VTE风险。例如，循环中肿瘤衍生的组织因子阳性微泡水平升高可能引发VTE。在卵巢癌小鼠模型中，肿瘤衍生的白细胞介素-6和肝脏血小板生成素与血小板生成增加和血栓形成有关。此外，乳腺癌和肺癌小鼠模型显示，肿瘤衍生的粒细胞集落刺激因子会导致中性粒细胞增多和中性粒细胞活化。活化的中性粒细胞可释放增强血栓形成的中性粒细胞胞外陷阱（NETs）。癌细胞来源的血液中的游离DNA、NETs以及细胞毒性药物治疗均可激活凝血级联反应。这些研究表明，不同类型癌症患者发生VTE存在多种机制。预防和治疗癌症患者的VTE具有挑战性；目前的建议是使用低分子量肝素。了解潜在机制可能有助于开发新的疗法，以安全地预防癌症患者的VTE。
