Characterization of a prothrombotic phenotype using thrombin generation and thrombin activity in cirrhosis and portal hypertension.

Abstract

BACKGROUND:

Patients with advanced chronic liver disease (ACLD) may develop a prothrombotic phenotype that seems to be more pronounced with more severe liver dysfunction. An imbalance of endogenous pro- and anticoagulants is not fully captured by routine coagulation assays.

METHODS:

In a cohort of ACLD patients undergoing hepatic venous pressure gradient (HVPG) measurement, we assessed thrombin generation (TGA) using two commercially available assays (Technothrombin and Thrombinoscope) with and without addition of soluble thrombomodulin (TM), as well as thrombin activity, alongside a panel of coagulation parameters.

RESULTS:

The cohort encompassed 37 patients (median age 55.3 years, mean HVPG 16 ± 5 mm Hg). In the TM-modified Thrombinoscope TGA, the endogenous thrombin generation potential (ETP) was significantly increased in Child-Pugh-Score (CPS) B/C patients (N = 23, 62 %) compared to CPS A patients (N = 14, 38 %) (ETP: 546 nM∗min (443-696) vs. 404 nM∗min (289-573), p = 0.028). Using the Technothrombin TGA without TM, patients with CPS B/C had decreased ETP compared to CPS A patients (ETP: 2792 ± 1336 nM∗min vs. 5040 ± 816 nM∗min, p < 0.001) and with addition of TM (final concentration: 5 nM; ETP: 2545 ± 1327 nM∗min vs. 4824 ± 929 nM∗min, p < 0.001). Thrombin activity levels were 0.6pM in median (0.2-1.6pM) and above the level of detectability (0.10pM) in 94.6 % of patients but were not correlated to severity of cirrhosis (CPS A 0.7pM vs CPS B/C 0.4pM, p = 0.377) nor to parameters of TGA.

CONCLUSION:

Thrombin plasma levels are elevated in liver disease patients without apparent correlation to TGA or severity of cirrhosis. TGAs can be modified with TM to enable protein C-dependent anticoagulation, but result in differences with regard to severity of liver disease.

• Authors: Oliver Königsbrügge, Bernhard Scheiner, Benedikt Simbrunner, Georg Semmler, Peter Quehenberger, Ingrid Pabinger-Fasching, Michael Trauner, Mattias Mandorfer, Ton Lisman, Cihan Ay, Thomas Reiberger
• Journal: Thrombosis research (Thromb Res) Vol. 222 Pg. 124-130 (02 2023) ISSN: 1879-2472 [Electronic] United States
• PMID: 36646026 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Thrombin

Topics

• Humans
• Thrombin (metabolism)
• Liver Cirrhosis (complications)
• Blood Coagulation
• Hypertension, Portal
• Phenotype