Year: 2025
Type: article
Study design: Observational Study
Abstract: Background & Aims: The role of protease nexin 1 (PN-1), a serine protease inhibitor that regulates both coagulation and fibrinolysis, is unknown in patients with cirrhosis. This study aimed to provide a comprehensive assessment of the role of PN-1 in cirrhosis. Methods: Plasma PN-1 concentration in 212 patients with advanced chronic liver disease and 30 healthy individuals was measured by ELISA. The role of PN-1 was investigated using thrombin generation assay, rotational thromboelastometry, and clot lysis assay in platelet-rich plasma and platelet-free plasma from 10 patients with stable decompensated cirrhosis and 10 healthy individuals. Results: = 0.0001), strongly increased with liver disease severity and portal hypertension, and was associated with 1-year mortality. In patients with stable decompensated cirrhosis, the synergy between platelet PN-1 and thrombomodulin to inhibit thrombin generation, observed in healthy individuals, was lost. Importantly, platelet PN-1 inhibition induced a much greater acceleration of fibrinolysis in patients with cirrhosis than in healthy individuals (1.6 and 2.8 times greater reduction in lysis onset time and lysis index 30, respectively, without tPA). Unlike platelet PN-1, plasma PN-1 plays a negligible role in coagulation and fibrinolysis. Conclusions: Platelet-derived PN-1 was found to markedly limit fibrinolysis in decompensated cirrhosis, although its impact on coagulation appeared minimal. Although elevated plasma PN-1 concentrations were observed in patients with advanced chronic liver disease, they did not contribute to hemostasis regulation. Overall, PN-1 should be added to the list of hemostasis factors that are dysregulated in cirrhosis. Impact and implications: The role of PN-1, a serpin that regulates both coagulation and fibrinolysis, is unknown in cirrhosis. PN-1 appears as an important regulator of fibrinolysis in patients with cirrhosis. The role of PN-1 (and platelets more broadly) should be taken into account when assessing fibrinolysis in patients with cirrhosis.
Source: JHEP Reports
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,110
Awards: DECOMPENSATED CIRRHOSIS: IDENTIFICATION OF NEW COMBINATORIAL THERAPIES BASED ON SYSTEMS APPROACHES, TimE frame ControL of Inflammation by canonical and non-canonical autophagy to Prevent fatty liver diSease progrEssion, JAK2V617F clonality profile: identification of cell types involved in myeloproliferative disorders-associated thrombosis, G4077682647, G434337789, G4656594441, G4667364679, G5186833093, Deciphering HEArt-liVEr commuNication in nonalcohoLic fattY liver disease, TArgeting protease nexin-1 To prevenT liver fibRosis progression And bleeding ComplicaTIOns in cIrrhosiS, G7090315418, G8471630636, Université de Paris
OpenAlex ID: W4413652324