Patients with cirrhosis have a disbalance between coagulation and fibrinolysis resulting in a prothrombotic phenotype

Ruth Anne Laura Willems*, Alberto Zanetto, Elena Campello, Ilaria de Simone, Cristiana Bulato, Joke Konings, Matthijs Kramer, Samia Tufaha, Francesco Paolo Russo, Marco Senzolo, Patrizia Burra, Hugo Ten Cate, Judith de Vos-Geelen, Mark Roest, Paolo Simioni, Bas de Laat, Dana Huskens

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: Patients with cirrhosis develop multiple hemostatic alterations. Although fibrinolysis is also affected by liver disease, studies have produced conflicting results, highlighting the need for a reliable fibrinolysis assay. Assessing the kinetics of plasmin generation (PG) is a new method to study the fibrinolytic state of cirrhosis patients. OBJECTIVES: This study aimed to compare fibrinolysis between patients with cirrhosis and healthy subjects. METHODS: This single-center cohort study included cirrhosis patients from the Padova University Hospital. Fibrinolysis and hemostasis were assessed with PG, thrombin generation (TG), and clot lysis time (CLT). To quantify malalignment between TG and PG, ratios were calculated. RESULTS: In total, 101 patients with cirrhosis (Child-Pugh A/B/C: 36/24/41) were included and 20 healthy subjects. Compared with healthy subjects, patients showed a significantly lower endogenous plasmin potential (EPP) and plasmin peak. PG capacity decreased with liver disease severity. The lag-time to PG was prolonged in patients. No differences in endogenous thrombin potential (ETP) and lag-time were found when comparing TG profiles. Patients had a shorter CLT. Increased TG/PG ratios for the EPP and plasmin peak were found in patients, compared to controls. TG/PG ratios increased with liver disease severity. CONCLUSIONS: Patients with cirrhosis have a complex fibrinolytic profile, with a delayed and decreased capacity to generate plasmin and a more rapid clot lysis. A disbalance was found between coagulation and fibrinolysis, with a normal to increased TG capacity and a decreased PG capacity. These results support the theory that cirrhosis patients are in a prothrombotic state.
Original languageEnglish
JournalJournal of Thrombosis and Haemostasis
DOIs
Publication statusE-pub ahead of print - 6 Mar 2025

Keywords

  • Blood Coagulation
  • Cirrhosis
  • Fibrinolysis
  • Thrombosis

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