Reddel Caroline J, Tan Chuen Wen, Chen Vivien M
ANZAC Research Institute, University of Sydney, Concord 2139, Australia.
Department of Haematology, Singapore General Hospital, Singapore 169608, Singapore.
Cancers (Basel). 2019 Jan 16;11(1):100. doi: 10.3390/cancers11010100.
The high occurrence of cancer-associated thrombosis is associated with elevated thrombin generation. Tumour cells increase the potential for thrombin generation both directly, through the expression and release of procoagulant factors, and indirectly, through signals that activate other cell types (including platelets, leukocytes and erythrocytes). Furthermore, cancer treatments can worsen these effects. Coagulation factors, including tissue factor, and inhibitors of coagulation are altered and extracellular vesicles (EVs), which can promote and support thrombin generation, are released by tumour and other cells. Some phosphatidylserine-expressing platelet subsets and platelet-derived EVs provide the surface required for the assembly of coagulation factors essential for thrombin generation in vivo. This review will explore the causes of increased thrombin production in cancer, and the availability and utility of tests and biomarkers. Increased thrombin production not only increases blood coagulation, but also promotes tumour growth and metastasis and as a consequence, thrombin and its contributors present opportunities for treatment of cancer-associated thrombosis and cancer itself.
癌症相关血栓形成的高发生率与凝血酶生成增加有关。肿瘤细胞通过表达和释放促凝因子直接增加凝血酶生成的可能性，也通过激活其他细胞类型（包括血小板、白细胞和红细胞）的信号间接增加凝血酶生成的可能性。此外，癌症治疗会使这些影响恶化。包括组织因子在内的凝血因子以及凝血抑制剂会发生改变，肿瘤细胞和其他细胞会释放可促进和支持凝血酶生成的细胞外囊泡（EVs）。一些表达磷脂酰丝氨酸的血小板亚群和血小板衍生的EVs为体内凝血酶生成所必需的凝血因子组装提供了所需的表面。本综述将探讨癌症中凝血酶产生增加的原因，以及检测方法和生物标志物的可用性及实用性。凝血酶产生增加不仅会增强血液凝固，还会促进肿瘤生长和转移，因此，凝血酶及其相关因素为治疗癌症相关血栓形成和癌症本身提供了机会。
