【输血医学基础】静脉血栓形成机制的最新报道汇集

内皮功能障碍和由此产生的炎症细胞粘附分子的上调，导致血管疾病的发展^1-3。炎症细胞分泌细胞因子/趋化因子和生长因子，诱导血管内皮损伤，促进血管平滑肌细胞增殖⁴。反之，激活的内皮细胞和血管平滑肌细胞分泌多种因子，这些因子激活血小板和凝血溶蛋白系统。这些因素也以自分泌/旁分泌的方式影响血管细胞本身^8-9。在血管活性因子的分泌过程中，Rho激酶系统的过度和持续激活在活性氧的产生中起着至关重要的作用。此外，过量的活性氧(氧化应激)导致内皮损伤¹³，可以增强粘附分子的表达，激活血小板和凝血系统^{8,14- 24}。

静脉血栓栓塞(VTE)包括深部静脉血栓形成和肺血栓栓塞^27-28。肺血栓栓塞是最强危机生命的静脉血栓栓塞，停止抗凝治疗后复发率较高。深静脉血栓形成常与肺血栓栓塞有关，住院患者发生静脉血栓栓塞的风险很高。主要的高风险因素有遗传基因的改变，肥胖、药物、怀孕、衰老、创伤和恶性肿瘤。有研究表明，在老鼠体内证实胰腺癌细胞来源的微泡可诱导血栓形成。甚至，还研究得出肿瘤来源微粒表达组织因子（TF）²⁸。另有研究表明微囊泡通过新的途径诱导血栓形成³¹。另外，绝经前女性服用激素避孕患静脉血栓栓塞的风险高。预测VTE复发的因素包括高龄、肥胖、男性、活动性癌症、近端深静脉血栓形成、停止抗凝治疗后D-二聚体水平升高²⁹，抗磷脂综合征，抗凝血酶、蛋白C或蛋白S缺乏，妊娠以及小于3个月的抗凝治疗。内皮损伤、瘀血和血液高凝是静脉血栓形成的重要原因²⁷。促炎细胞因子/趋化因子在内皮激活、损伤及粘附分子表达也可促进血栓形成^33-35。静脉血栓和动脉血栓的形成机制不同。特别是静脉血栓形成主要归因于静脉血液停滞³⁷。最新研究报道，Nosaka等人研究得出肿瘤坏死因子受体55(TNF-Rp55)缺失，延迟静脉血栓的消退。在小鼠静脉血栓模型中，他们阐明TNFα-TNF-Rp55轴，可通过增强纤维蛋白溶解和胶原溶解，在深静脉血栓形成中发挥抗血栓作用。传统抗凝治疗主要用于预防肺血栓栓塞，也可防止深静脉血栓栓子生长，却增加了出血的发生率^28,38。

然而，Nosaka等人的研究提示TNFα-TNF-Rp55轴可能是一个血栓溶解的新靶点³⁶。最近一期《动脉硬化、血栓和血管生物学》杂志报道，体外静脉血栓形成模型中证实了血小板以红细胞压积和糖蛋白VI依赖的方式驱动血栓传播。更有意义的是研究者们开发了一种体外微流控模型系统来深入研究血栓形成^39-40。

关键词：静脉血栓；静脉血栓栓塞(VTE)；血栓溶解；内皮功能障碍；炎症细胞粘附分子

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投稿人：年青

投稿时间：2021年12月4日

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ꁹ后一个：无