Thrombotic and Hemorrhagic Disease Unit, Department of Medicine, University of Padova, Padova, Italy.
Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.
Thromb Haemost. 2018 Feb;118(2):251-265. doi: 10.1160/TH17-08-0596. Epub 2018 Jan 29.
Cancer induces a systemic hypercoagulable state that elevates the baseline thrombotic risk of affected patients. This hypercoagulable state reflects a complex interplay between cancer cells and host cells and the coagulation system as part of the host response to cancer. Although the tissue factor (TF)/factor VIIa pathway is proposed to be the principal initiator of fibrin formation in cancer patients, clinical studies have not shown a consistent relationship between circulating TF levels (often measured as plasma microvesicle-associated TF) and the risk of thrombosis. A renewed interest in the role of the contact pathway in thrombosis has evolved over the past decade, raising the question of its role in the pathogenesis of thrombotic complications in cancer. Recent observations have documented the presence of activation of the contact system in gastrointestinal, lung, breast and prostate cancers. Although the assays used to measure contact activation differ, and despite the absence of standardization of methodologies, it is clear that both the intrinsic and extrinsic pathways may be activated in cancer. This review will focus on recent findings concerning the role of activation of the contact system in cancer-associated hypercoagulability and thrombosis. An improved understanding of the pathophysiology of these mechanisms may lead to personalized antithrombotic protocols with improved efficacy and safety compared with currently available therapies.
癌症会导致全身性高凝状态，使受影响患者的基线血栓形成风险升高。这种高凝状态反映了癌细胞和宿主细胞与凝血系统之间的复杂相互作用，是宿主对癌症反应的一部分。虽然组织因子 (TF)/因子 VIIa 途径被认为是癌症患者纤维蛋白形成的主要启动子，但临床研究并未显示循环 TF 水平（通常作为血浆微囊泡相关 TF 测量）与血栓形成风险之间存在一致关系。过去十年中，人们对接触途径在血栓形成中的作用重新产生了兴趣，这引发了其在癌症血栓并发症发病机制中的作用的问题。最近的观察结果记录了胃肠道、肺、乳腺和前列腺癌中接触系统的激活。尽管用于测量接触激活的测定方法不同，并且尽管缺乏方法学的标准化，但显然内在和外在途径都可能在癌症中被激活。这篇综述将重点介绍关于接触系统激活在癌症相关高凝状态和血栓形成中的作用的最新发现。对这些机制的病理生理学的更好理解可能会导致与目前可用的治疗方法相比，具有更好疗效和安全性的个体化抗血栓形成方案。
