首页|Intraperitoneal Activation of Coagulation and Fibrinolysis in Patients with Cirrhosis and Ascites

Intraperitoneal Activation of Coagulation and Fibrinolysis in Patients with Cirrhosis and Ascites

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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.

cirrhosisascitescoagulationfibrinolysis

Johannes Thaler、Ton Lisman、Peter Quehenberger、Lena Hell、Philipp Schwabl、Bernhard Scheiner、Theresa Bucsics、Rienk Nieuwland、Cihan Ay、Michael Trauner、Ingrid Pabinger、Thomas Reiberger、Mattias Mandorfer

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Division of Haematology and Haemostaseology, Department of Internal Medicine I, Medical University

Department of Surgery, Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver

Department of Laboratory Medicine, Medical University of Vienna

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical

Laboratory of Experimental Clinical Chemistry, Vesicle Observation Centre, Academic Medical Center

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2022

Thrombosis and Haemostasis

Thrombosis and Haemostasis

SCI
ISSN:0340-6245
年,卷(期):2022.122(3)
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