Nadir Yona, Brenner Benjamin
Thrombosis and Hemostasis Unit, Department of Hematology, Rambam Health Care Campus, Haifa, Israel.
Rambam Maimonides Med J. 2018 Sep 2;9(4):1-7. doi: 10.5041/RMMJ.10349.
Cancer patients have a pro-thrombotic state attributed to the ability of cancer cells to activate the coagulation system and interact with hemostatic cells, thus tilting the balance between pro- and anticoagulants. Mechanisms underlying the coagulation system activation involve tumor cells, endothelial cells, platelets, and white blood cells. Anti-cancer therapies, including anti-angiogenic drugs, significantly increase the risk of thrombosis during treatment. Along with the role of coagulation proteins in the hemostatic system, these proteins also serve as growth factors to the tumor. Heparanase is a pro-angiogenic and pro-metastatic protein. Our previous studies have demonstrated that it enhances tissue factor (TF) activity and is present at high levels in tumor cells and patients' blood. Strategies to attenuate heparanase effects by heparin mimetics or peptides interrupting the TF-heparanase interaction are good candidates to attenuate tumor growth and thrombotic manifestations.
癌症患者存在促血栓形成状态，这归因于癌细胞激活凝血系统并与止血细胞相互作用的能力，从而打破了促凝剂和抗凝剂之间的平衡。凝血系统激活的潜在机制涉及肿瘤细胞、内皮细胞、血小板和白细胞。包括抗血管生成药物在内的抗癌疗法在治疗期间会显著增加血栓形成的风险。除了凝血蛋白在止血系统中的作用外，这些蛋白还可作为肿瘤的生长因子。乙酰肝素酶是一种促血管生成和促转移蛋白。我们之前的研究表明，它可增强组织因子（TF）活性，并且在肿瘤细胞和患者血液中含量很高。通过肝素模拟物或中断TF-乙酰肝素酶相互作用的肽来减弱乙酰肝素酶作用的策略，是减弱肿瘤生长和血栓形成表现的良好候选方法。
