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Thromb Haemost 2023; 123(12): 1140-1150
DOI: 10.1055/s-0043-1771187
Cellular Haemostasis and Platelets

Platelet Function Decreases with Increasing Severity of Liver Cirrhosis and Portal Hypertension—A Prospective Study

Ksenia Brusilovskaya 
1   Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
2   Vienna Hepatic Hemodynamic Experimental (HEPEX) Lab, Medical University of Vienna, Vienna, Austria
3   Christian-Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
,
Benedikt Silvester Hofer 
1   Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
2   Vienna Hepatic Hemodynamic Experimental (HEPEX) Lab, Medical University of Vienna, Vienna, Austria
3   Christian-Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
,
Benedikt Simbrunner 
1   Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
2   Vienna Hepatic Hemodynamic Experimental (HEPEX) Lab, Medical University of Vienna, Vienna, Austria
3   Christian-Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
4   Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
,
Beate Eichelberger
5   Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria
,
Silvia Lee
6   Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
David J. M. Bauer 
1   Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
4   Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
,
Mattias Mandorfer 
1   Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
4   Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
,
Philipp Schwabl 
1   Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
2   Vienna Hepatic Hemodynamic Experimental (HEPEX) Lab, Medical University of Vienna, Vienna, Austria
3   Christian-Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
4   Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
,
Simon Panzer
5   Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria
,
Thomas Reiberger 
1   Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
2   Vienna Hepatic Hemodynamic Experimental (HEPEX) Lab, Medical University of Vienna, Vienna, Austria
3   Christian-Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
4   Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
,
Thomas Gremmel 
6   Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
7   Department of Internal Medicine I, Cardiology and Intensive Care Medicine, Landesklinikum Mistelbach-Gänserndorf, Mistelbach, Austria
8   Institute of Cardiovascular Pharmacotherapy and Interventional Cardiology, Karl Landsteiner Society, St. Pölten, Austria
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Abstract

Background Cirrhotic patients display an increased risk for both bleeding and thrombosis. We investigated platelet activation across Child–Pugh stages (CPSs) and portal hypertension (PH) severity.

Material and Methods A total of 110 cirrhotic patients were prospectively included. CPS and hepatic venous pressure gradient (HVPG) were determined. Platelet surface expression of P-selectin and activated glycoprotein (GP) IIb/IIIa were measured by flow cytometry before/after stimulation with protease-activated receptor (PAR)-1 (thrombin receptor activating peptide, TRAP) and PAR-4 (AYPGKF) agonists, epinephrine, and lipopolysaccharide (LPS).

Results Platelet count was similar across CPS but lower with increasing PH severity. Expression of P-selectin and activated GPIIb/IIIa in response to TRAP and AYPGKF was significantly reduced in platelets of CPS-B/C versus CPS-A patients (all p < 0.05). Platelet P-selectin expression upon epinephrine and LPS stimulation was reduced in CPS-C patients, while activated GPIIb/IIIa in response to these agonists was lower in CPS-B/C (all p < 0.05). Regarding PH severity, P-selectin and activated GPIIb/IIIa in response to AYPGKF were lower in HVPG ≥20 mmHg patients (both p < 0.001 vs. HVPG < 10 mmHg). Similarly, activated GPIIb/IIIa was lower in HVPG ≥20 mmHg patients after TRAP stimulation (p < 0.01 vs. HVPG < 10 mmHg). The lower platelet surface expression of P-selectin and activated GPIIb/IIIa upon stimulation of thrombin receptors (PAR-1/PAR-4) in CPS-B/C and HVPG ≥20 mmHg patients was paralleled by reduced antithrombin-III levels in those patients (all p < 0.05). Overall, PAR-1- and PAR-4-mediated platelet activation correlated with antithrombin-III levels (p < 0.001).

Conclusion Platelet responsiveness decreases with increasing severity of liver cirrhosis and PH but is potentially counterbalanced by lower antithrombin-III levels.

Keywords

advanced chronic liver disease - portal hypertension - flow cytometry - platelet function - platelet activation

Authors' Contribution

Guarantor of the article: T.G. Data collection: K.B., B.S.H., B.S., B.E., D.J.M.B., P.S., M.M., T.R., T.G. Statistical analysis: K.B., B.S.H., T.R., T.G. Drafting of the manuscript: K.B., T.R., T.G. Study supervision: T.R., T.G. Revision for important intellectual content and approval of the final version of the manuscript: all authors.


Supplementary Material



Publication History

Received: 23 December 2022

Accepted: 14 June 2023

Article published online:
30 July 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
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