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: Tranexamic acid (TXA) reduces mortality in patients with massive hemorrhage by inhibiting fibrinolysis. However, it is associated with an increased risk of thrombosis. The activation of neutrophil extracellular traps (NETs) has been implicated in the formation of thrombosis. This study investigated the effects of tranexamic acid on circulating and localized NETs, neutrophils, platelets, and the vascular endothelium in a mouse model of thrombosis. : A ferric chloride-induced thrombosis mouse model was used and divided into five groups: a Control group that received intraperitoneal phosphate-buffered saline (PBS), and four experimental groups that received intraperitoneal tranexamic acid at doses of 5 mg/kg, 10 mg/kg, 20 mg/kg, and 30 mg/kg, respectively. To evaluate the expression of circulating and localized NETs, neutrophils, platelets, vascular endothelial cells, fibrinogen, and D-dimer, the following markers were analyzed: myeloperoxidase (MPO), neutrophil marker, cluster of differentiation (CD)31, CD34, fibrinogen α-chain, and D-dimer. These markers were assessed using flow cytometry, immunohistofluorescence staining, and Western blot analysis. The primary endpoint was the differential expression of anti-MPO antibody among the groups. : In total, data from 20 thrombosis mouse models were analyzed. For each group, four samples were assessed by flow cytometry, and three samples by immunohistofluorescence staining and Western blot analysis, respectively. In the flow cytometric analysis, circulating anti-MPO antibody expression was significantly higher in the TXA 20 and TXA 30 groups compared to the Control group ( = 0.001 and = 0.001, respectively). Immunohistofluorescence staining revealed that D-dimer expression in the thrombotic femoral artery was significantly lower in the TXA 5, TXA 10, and TXA 20 groups compared to the Control group ( = 0.005; = 0.018; = 0.004, respectively), but significantly higher in the TXA 30 group than in the Control group ( = 0.044). Similarly, the expression of anti-fibrinogen antibody was significantly lower in the TXA 5, TXA 10, and TXA 20 groups compared to the Control group ( = 0.038; = 0.003; = 0.041, respectively). Western blot analysis showed no significant differences in the expression of anti-Ly6B.2, anti-fibrinogen, and anti-CD31 antibodies among the groups. : The present study suggests that high-dose tranexamic acid (30 mg/kg) administration may increase circulating NETs and localized D-dimer levels, indicating a higher potential for thrombosis in a thrombosis mouse model. These findings imply that the prothrombotic effects of tranexamic acid may be dose-dependent and could vary based on underlying disease conditions. Therefore, the careful dosage adjustment of tranexamic acid may be necessary, particularly in patients at risk of thrombosis.

氨甲环酸（TXA）通过抑制纤维蛋白溶解降低大出血患者的死亡率。然而，它与血栓形成风险增加有关。中性粒细胞胞外陷阱（NETs）的激活与血栓形成有关。本研究在血栓形成小鼠模型中研究了氨甲环酸对循环和局部NETs、中性粒细胞、血小板及血管内皮的影响。

使用氯化铁诱导的血栓形成小鼠模型，并将其分为五组：接受腹腔注射磷酸盐缓冲盐水（PBS）的对照组，以及分别接受腹腔注射5mg/kg、10mg/kg、20mg/kg和30mg/kg氨甲环酸的四个实验组。为了评估循环和局部NETs、中性粒细胞、血小板、血管内皮细胞、纤维蛋白原和D-二聚体的表达，分析了以下标志物：髓过氧化物酶（MPO）、中性粒细胞标志物、分化簇（CD）31、CD34、纤维蛋白原α链和D-二聚体。使用流式细胞术、免疫组织荧光染色和蛋白质印迹分析评估这些标志物。主要终点是各组间抗MPO抗体的差异表达。

总共分析了20个血栓形成小鼠模型的数据。对于每组，分别通过流式细胞术评估4个样本，通过免疫组织荧光染色和蛋白质印迹分析评估3个样本。在流式细胞术分析中，与对照组相比，TXA 20组和TXA 30组中循环抗MPO抗体表达显著更高（分别为P = 0.001和P = 0.001）。免疫组织荧光染色显示，与对照组相比，TXA 5组、TXA 10组和TXA 20组中血栓形成的股动脉中D-二聚体表达显著更低（分别为P = 0.005；P = 0.018；P = 0.004），但TXA 30组中显著高于对照组（P = 0.044）。同样，与对照组相比，TXA 5组、TXA 10组和TXA 20组中抗纤维蛋白原抗体表达显著更低（分别为P = 0.038；P = 0.003；P = 0.041）。蛋白质印迹分析显示各组间抗Ly6B.2、抗纤维蛋白原和抗CD31抗体表达无显著差异。

本研究表明，高剂量氨甲环酸（30mg/kg）给药可能增加循环NETs和局部D-二聚体水平，表明在血栓形成小鼠模型中血栓形成潜力更高。这些发现意味着氨甲环酸的促血栓形成作用可能是剂量依赖性的，并且可能因潜在疾病状况而异。因此，可能有必要仔细调整氨甲环酸的剂量，特别是在有血栓形成风险的患者中。