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Intraperitoneal Activation of Coagulation and Fibrinolysis in Patients with Cirrhosis and Ascites
Thrombosis and Haemostasis ( IF 6.7 ) Pub Date : 2021-05-21 , DOI: 10.1055/a-1515-9529
Johannes Thaler 1 , Ton Lisman 2 , Peter Quehenberger 3 , Lena Hell 1 , Philipp Schwabl 4, 5 , Bernhard Scheiner 4, 5 , Theresa Bucsics 4, 5 , Rienk Nieuwland 6 , Cihan Ay 1 , Michael Trauner 4, 5 , Ingrid Pabinger 1 , Thomas Reiberger 4, 5 , Mattias Mandorfer 4, 5
Affiliation  

Development of ascites is the most common form of decompensation of cirrhosis. We aimed to investigate the coagulation system in ascitic fluid and plasma of patients with cirrhosis. We determined coagulation parameters and performed clotting and fibrinolysis experiments in ascitic fluid and plasma of thoroughly characterized patients with cirrhosis and ascites (n = 25) and in plasma of patients with cirrhosis but without ascites (n = 25), matched for severity of portal hypertension. We also investigated plasma D-dimer levels in an independent cohort of patients (n = 317) with clinically significant portal hypertension (HVPG ≥ 10 mmHg), grouped according to ascites severity. Ascitic fluid was procoagulant in a clotting assay. The procoagulant potential of ascitic fluid was abolished by depletion of extracellular vesicles from ascitic fluid by filtration or by addition of a tissue factor-neutralizing antibody. Compared with plasma, extracellular vesicle-associated tissue factor activity was high in ascitic fluid, while activities of other coagulation factors were low. The extracellular vesicle-depleted fraction of ascitic fluid induced fibrinolysis, which was prevented by aprotinin, indicating the presence of plasmin in ascitic fluid. Plasma peak thrombin generation and parameters reflecting fibrinolysis were independently associated with the presence of ascites. Finally, plasma D-dimer levels were independently linked to ascites severity in our second cohort comprising 317 patients. In conclusion, coagulation and fibrinolysis become activated in ascites of patients with cirrhosis. While tissue factor-exposing extracellular vesicles in ascitic fluid seem unable to pass the peritoneal membrane, fibrinolytic enzymes get activated in ascitic fluid and may re-enter the systemic circulation and induce systemic fibrinolysis.

中文翻译:

肝硬化腹水患者的腹腔内凝血和纤溶激活

腹水的发展是肝硬化失代偿的最常见形式。我们旨在研究肝硬化患者腹水和血浆中的凝血系统。我们确定了凝血参数,并在完全表征的肝硬化和腹水患者(n = 25)的腹水和血浆以及肝硬化但没有腹水的患者(n = 25)的血浆中进行了凝血和纤溶实验,与门静脉高压症的严重程度相匹配. 我们还调查了根据腹水严重程度分组的具有临床意义的门静脉高压症(HVPG ≥ 10 mmHg)的独立患者队列(n = 317)的血浆 D-二聚体水平。腹水在凝血试验中是促凝剂。通过过滤或添加组织因子中和抗体从腹水中去除细胞外囊泡,从而消除了腹水的促凝血潜力。与血浆相比,腹水中细胞外囊泡相关组织因子活性较高,而其他凝血因子活性较低。腹水的细胞外囊泡耗尽部分诱导纤溶,抑肽酶阻止了纤溶,表明腹水中存在纤溶酶。血浆凝血酶生成峰值和反映纤维蛋白溶解的参数与腹水的存在独立相关。最后,在我们包含 317 名患者的第二个队列中,血浆 D-二聚体水平与腹水严重程度独立相关。综上所述,肝硬化患者腹水中的凝血和纤维蛋白溶解被激活。虽然腹水中暴露组织因子的细胞外囊泡似乎无法通过腹膜,但纤维蛋白溶解酶在腹水中被激活并可能重新进入体循环并诱导全身纤维蛋白溶解。
更新日期:2021-07-05
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