Thrombotic and Haemorrhagic Disease Unit, Department of Medicine, University of Padova, Padova, Italy.
Division of Haematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Br J Cancer. 2019 Aug;121(5):359-371. doi: 10.1038/s41416-019-0510-x. Epub 2019 Jul 22.
It has long been recognised that pancreatic cancer induces a hypercoagulable state that may lead to clinically apparent thrombosis. Although the relationship between pancreatic cancer and hypercoagulability is well described, the underlying pathological mechanism(s) and the interplay between these pathways remain a matter of intensive study. This review summarises existing data on epidemiology and pathogenesis of thrombotic complications in pancreatic cancer with a particular emphasis on novel pathophysiological pathways. Pancreatic cancer is characterised by high tumoural expression of tissue factor, activation of leukocytes with the release of neutrophil extracellular traps, the dissemination of tumour-derived microvesicles that promote hypercoagulability and increased platelet activation. Furthermore, other coagulation pathways probably contribute to these processes, such as those that involve heparanase, podoplanin and hypofibrinolysis. In the era in which heparin and its derivatives-the currently recommended therapy for cancer-associated thrombosis-might be superseded by direct oral anticoagulants, novel data from mouse models of cancer-associated thrombosis suggest the possibility of future personalised therapeutic approaches. In this dynamic era for cancer-associated thrombosis, the discovery of novel prothrombotic and proinflammatory mechanisms will potentially uncover pharmacological targets to prevent and treat thrombosis without adversely affecting haemostasis.
长期以来，人们已经认识到胰腺癌会导致高凝状态，从而可能导致临床上明显的血栓形成。尽管胰腺癌与高凝状态之间的关系已得到很好的描述，但潜在的病理机制和这些途径之间的相互作用仍然是深入研究的课题。本文综述了目前关于胰腺癌血栓并发症的流行病学和发病机制的现有数据，特别强调了新的病理生理途径。胰腺癌的特点是肿瘤组织因子表达水平高，白细胞被激活并释放中性粒细胞细胞外陷阱，肿瘤衍生的微泡扩散，促进高凝状态和血小板激活增加。此外，其他凝血途径可能也参与了这些过程，例如涉及肝素酶、足细胞蛋白和纤溶不足的途径。在肝素及其衍生物（目前推荐用于癌症相关血栓形成的治疗药物）可能被直接口服抗凝剂取代的时代，来自癌症相关血栓形成的小鼠模型的新数据表明，未来可能会采用个性化的治疗方法。在癌症相关血栓形成的这一动态时代，新的促血栓形成和促炎机制的发现将有可能发现预防和治疗血栓形成的药理学靶点，而不会对止血产生不利影响。
