Hamostaseologie 2025; 45(S 01): S21
DOI: 10.1055/s-0044-1801571
Abstracts
Topics
T-04 Coagulation and fibrinolysis

Parameters impacting fibrinolysis in patients with liver cirrhosis

Authors

  • L A Gautier

    1   Lausanne University Hospital (CHUV) and University of Lausanne, Division of Hematology and Central Hematology Laboratory, Lausanne, Switzerland

  • I De Simone

    2   Synapse Research Institute, Maastricht, Netherlands

  • A Aliotta

    1   Lausanne University Hospital (CHUV) and University of Lausanne, Division of Hematology and Central Hematology Laboratory, Lausanne, Switzerland

  • L Veuthey

    1   Lausanne University Hospital (CHUV) and University of Lausanne, Division of Hematology and Central Hematology Laboratory, Lausanne, Switzerland

  • D Huskens

    2   Synapse Research Institute, Maastricht, Netherlands

  • B de Laat

    2   Synapse Research Institute, Maastricht, Netherlands

  • C Pereira Portela

    1   Lausanne University Hospital (CHUV) and University of Lausanne, Division of Hematology and Central Hematology Laboratory, Lausanne, Switzerland

  • M G Zermatten

    1   Lausanne University Hospital (CHUV) and University of Lausanne, Division of Hematology and Central Hematology Laboratory, Lausanne, Switzerland

  • M Fraga

    3   Lausanne University Hospital (CHUV) and University of Lausanne, Division of Gastroenterology and Hepatology, Lausanne, Switzerland

  • D Bertaggia Calderara

    1   Lausanne University Hospital (CHUV) and University of Lausanne, Division of Hematology and Central Hematology Laboratory, Lausanne, Switzerland

  • L Alberio

    1   Lausanne University Hospital (CHUV) and University of Lausanne, Division of Hematology and Central Hematology Laboratory, Lausanne, Switzerland
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Introduction: Liver cirrhosis (LC) has a prevalence>1%, with an increase of over 80% in the last 30 years. LC is responsible for ca. 2% of deaths worldwide [1], notably due to thrombo-haemorrhagic complications. The mechanisms regulating fibrinolysis and its impact on LC complications remain to be investigated.

The aim of this study was to investigate fibrinolysis in plasma from patients with LC using (i) global fibrinolytic assay (GFA), (ii) calibrated plasmin generation (PG) assay, (iii) measurement of liver-produced proteins related to fibrinolysis, and to correlate the results with clinical events.

Method: Plasma samples were obtained from 150 patients with Child-A, -B and -C LC. Fibrinolysis was assessed by a GFA (Lysis Timer, Hyphen Biomed, Neuville-sur-Oise, France), which measures the time required to lyse a plasma clot induced by thrombin in the presence of calcium, silica, and tissue-type plasminogen activator (tPA). PG (Fluoroskan Ascent, Thrombinoscope, Maastricht, Netherlands) was induced by adding tPA to a plasma sample in which coagulation was triggered and assessed by a specific plasmin fluorogenic substrate. Measured PG parameters were lag time, velocity index (VI), time to peak, peak height (PH), and endogenous plasmin potential (EPP). In addition, fibrinogen (fbg), factor XIII (FXIII), plasminogen (plg), α2-antiplasmin (α2-AP), and thrombin-activatable fibrinolysis inhibitor (TAFI) were measured.

Results: The following results were observed:

GFA lysis time, plasma concentrations of liver-produced proteins involved in the fibrinolysis (fbg, FXIII, plg, α2-AP, TAFI) and PG were all significantly reduced as a function of increasing LC clinical severity (p<0.001).

GFA lysis time and FXIII concentration were significantly reduced in alcohol-induced LC compared to other aetiologies (p<0.05).

Patients with LC without portal hypertension (PHT) had a normal GFA lysis time, normal PG parameters (especially EPP, plasmin PH, plasmin VI), and normal concentrations of fbg, FXIII, plg, α2-AP and TAFI. Of note, these parameters were significantly lower in patients with PHT than in those without PHT (p<0.05).

GFA lysis time was strongly directly correlated (p<0.0001) with α2-AP (R2=0.47) and fbg (R2 =0.41) levels.

Conclusion: The concentrations of α2-AP and fbg, the stage of LC, and the presence of PHT seem to be crucial for the lysis time assessed by the GFA Lysis Timer in patients with LC. However, the lysis time was not able to predict the occurrence of thrombo-haemorrhagic events, which are mainly related to PHT. The development of other plasma lysis models focusing on either clot resistance or plasma lytic capacity is necessary to test their correlation with thrombo-haemorrhagic events in patients with LC.


 

Conflict of Interest:

Synapse Research Institute is part of the Diagnostica Stago group.

  • References

  • 1 GBD 2017 Cirrhosis Collaborators. 2020 &apos;The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017&apos;. Lancet Gastroenterol Hepatol 2020; 5 (03) 245-266
    CrossrefPubMedSearch in Google Scholar

Publication History

Article published online:
13 February 2025

© 2025. Thieme. All rights reserved.

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  • References

  • 1 GBD 2017 Cirrhosis Collaborators. 2020 &apos;The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017&apos;. Lancet Gastroenterol Hepatol 2020; 5 (03) 245-266
    CrossrefPubMedSearch in Google Scholar