A prothrombotic state is a typical feature of type 2 diabetes mellitus (T2DM). Apart from increased platelet reactivity, endothelial dysfunction, hyperfibrinogenemia, and hypofibrinolysis are observed in T2DM. A variety of poorly elucidated mechanisms behind impaired fibrinolysis in this disease have been reported, indicating complex associations between platelet activation, fibrin formation and clot structure, and fibrinolysis inhibitors, in particular, elevated plasminogen antigen inhibitor-1 levels which are closely associated with obesity. Abnormal fibrin clot structure is of paramount importance for relative resistance to plasmin-mediated lysis in T2DM. Enhanced thrombin generation, a proinflammatory state, increased release of neutrophil extracellular traps, elevated complement C3, along with posttranslational modifications of fibrinogen and plasminogen have been regarded to contribute to altered clot structure and impaired fibrinolysis in T2DM. Antidiabetic agents such as metformin and insulin, as well as antithrombotic agents, including anticoagulants, have been reported to improve fibrin properties and accelerate fibrinolysis in T2DM. Notably, recent evidence shows that hypofibrinolysis, assessed in plasma-based assays, has a predictive value in terms of cardiovascular events and cardiovascular mortality in T2DM patients. This review presents the current data on the mechanisms underlying arterial and venous thrombotic complications in T2DM patients, with an emphasis on hypofibrinolysis and its impact on clinical outcomes. We also discuss potential modulators of fibrinolysis in the search for optimal therapy in diabetic patients.

中文翻译：

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2 型糖尿病中的低纤维蛋白溶解及其临床意义：从机制到药理调节

血栓前状态是 2 型糖尿病 (T2DM) 的典型特征。除了血小板反应性增加外，在 T2DM 中还观察到内皮功能障碍、高纤维蛋白原血症和低纤维蛋白溶解。已经报道了这种疾病中纤溶障碍受损背后的多种机制尚不清楚，这表明血小板活化、纤维蛋白形成和凝块结构与纤溶抑制剂之间存在复杂的关联，特别是与肥胖密切相关的纤溶酶原抗原抑制剂 1 水平升高。异常的纤维蛋白凝块结构对于 T2DM 中对纤溶酶介导的裂解的相对抗性至关重要。凝血酶生成增强、促炎状态、中性粒细胞胞外陷阱释放增加、补体 C3 升高、与纤维蛋白原和纤溶酶原的翻译后修饰一起，已被认为有助于改变 T2DM 中的凝块结构和纤维蛋白溶解受损。据报道，二甲双胍和胰岛素等抗糖尿病药物以及抗血栓药物（包括抗凝剂）可改善 T2DM 中的纤维蛋白特性并加速纤维蛋白溶解。值得注意的是，最近的证据表明，在基于血浆的测定中评估的纤溶亢进对于 T2DM 患者的心血管事件和心血管死亡率具有预测价值。本综述介绍了关于 T2DM 患者动脉和静脉血栓并发症机制的当前数据，重点是纤溶不足及其对临床结果的影响。