Falanga Anna, Schieppati Francesca, Russo Domenico
Department of Immunohematology & Transfusion Medicine and the Hemostasis and Thrombosis Center, Hospital Papa Giovanni XXIII, Bergamo, Italy.
Unit of Blood Diseases and Stem Cell Transplantation, University of Brescia, Brescia, Italy.
Semin Thromb Hemost. 2015 Oct;41(7):756-64. doi: 10.1055/s-0035-1564040. Epub 2015 Sep 26.
Thrombosis is a major cause of morbidity and mortality in cancer patients. Many clinical factors contribute to the high thrombotic risk of this condition, including the type of malignancy, its disease stage, anticancer therapies, and comorbidities. However, the cancer cell-specific prothrombotic properties together with the host cell inflammatory response are important players in the pathogenesis of the cancer-associated hypercoagulability. Tissue factor (TF) is the most important procoagulant protein expressed by cancer cells, and with other cancer tissue procoagulant properties highly contributes to the procoagulant phenotype of malignant cells. Recent discoveries indicate that oncogenes determine the procoagulant protein expression, including TF, in cancer tissues. In addition, in malignancy, TF is also overexpressed by host normal blood cells triggered by cancer-derived inflammatory stimuli. As a consequence, a subclinical activation of blood coagulation is typically present in cancer patients, as demonstrated by abnormalities of circulating thrombotic biomarkers. The relevance of measuring these biomarkers to determine the patient thrombotic risk level is under active investigation. The goal is to identify the high-risk subgroups to establish more accurate and targeted anticoagulation strategies to prevent thrombosis in cancer patients. Ultimately, the clarification of specific molecular mechanisms triggering blood coagulation in specific cancer types may also indicate alternative ways to inhibit clotting activation in these conditions.
血栓形成是癌症患者发病和死亡的主要原因。许多临床因素导致了这种疾病的高血栓形成风险，包括恶性肿瘤的类型、疾病阶段、抗癌治疗以及合并症。然而，癌细胞特异性的促血栓形成特性以及宿主细胞的炎症反应在癌症相关高凝状态的发病机制中起着重要作用。组织因子（TF）是癌细胞表达的最重要的促凝蛋白，与其他癌症组织促凝特性一起对恶性细胞的促凝表型有很大贡献。最近的发现表明，癌基因决定了癌症组织中促凝蛋白的表达，包括TF。此外，在恶性肿瘤中，TF也会被癌症衍生的炎症刺激触发的宿主正常血细胞过度表达。因此，癌症患者通常存在凝血的亚临床激活，循环血栓生物标志物的异常证明了这一点。测量这些生物标志物以确定患者血栓形成风险水平的相关性正在积极研究中。目标是识别高危亚组，以建立更准确、有针对性的抗凝策略，预防癌症患者的血栓形成。最终，阐明特定癌症类型中触发凝血的具体分子机制，也可能为在这些情况下抑制凝血激活指明替代方法。
