血栓性炎症与深静脉血栓形成后综合征相关研究进展

Research progress related to thromboinflammation and post-thrombotic syndrome following deep vein thrombosis

深静脉血栓形成后综合征(PTS)是继发于深静脉血栓形成(DVT)的远期并发症,主要临床表现为患肢沉重不适、胀痛、水肿、溃疡等。由于PTS静脉壁纤维化不可逆,且常伴有管腔闭塞导致难愈溃疡形成,治疗方法十分有限且效果不确切。以往观点认为血栓形成后,随病程进展其静脉阻塞扩张和血栓机化再通导致静脉瓣功能受损,产生的静脉高压是引起PTS的主要发病机制。近年来发现静脉瘀滞环境下以中性粒细胞为主的无菌性炎症性血栓形成被异常激活,可启动凝血级联反应产生瀑布效应加剧血栓形成。在静脉血栓溶解阶段,巨噬细胞可通过分泌各类炎症因子促进血栓内新生血管形成等加速血栓溶解,亦可以影响静脉管壁降低顺应性,引起管腔纤维化并重塑不良导致PTS发生。本文主要聚焦血栓性炎症在静脉血栓形成、溶解和静脉壁纤维化不同阶段的作用,并围绕炎性标志物和相关抗炎靶点药物作一综述。

Post-thrombotic syndrome(PTS)is a long-term complication secondary to deep vein thrombosis(DVT),characterized by symptoms such as heaviness,pain,swelling,and ulcers in the affected limb.Due to the irreversible fibrosis of the venous wall in PTS,along with luminal occlusion leading to intractable ulcer formation,the treatment options are limited and their effectiveness is uncertain.Previous perspectives suggested that venous obstruction and dilation,as well as thrombus recanalization and valvular dysfunction,resulting from the progression of thrombosis,are the main pathogenic mechanisms leading to PTS.In recent years,it has been discovered that aseptic inflammatory thrombosis,primarily driven by neutrophils,is abnormally activated in a venous stasis environment.This activation can initiate a cascade of coagulation reactions,leading to intensified thrombus formation,known as the waterfall effect.During the phase of thrombus resolution, macrophages can promote neovascularization within the thrombus bysecreting various inflammatory factors, thereby accelerating thrombus dissolution. However, they canalso affect the venous wall, reducing compliance, inducing luminal fibrosis, and promoting unfavorableremodeling, ultimately contributing to the development of PTS. This article primarily focuses on the roleof thromboinflammation in different stages of venous thrombosis formation, lysis, and venous wallfibrosis, and provides a comprehensive review regarding inflammatory markers and relevant antiinflammatorytarget medications.