Hamostaseologie 2025; 45(S 01): S89-S90
DOI: 10.1055/s-0044-1801682
Abstracts
Topics
T-10 Platelets – Disorders of platelet function and numbers

Plasma factors might interfere with platelet function in patients with decompensated liver cirrhosis

Authors

  • G Kaur

    1   University Heart Center Freiburg Bad Krozingen, University of Freiburg, Department of Cardiology and Angiology, Freiburg, Germany

  • J P Huber

    2   University Hospital Freiburg, Faculty of Medicine, University of Freiburg, Department of Medicine II, Freiburg, Germany

  • S Zhang

    3   University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Mannheim, Germany

  • D Stallmann

    1   University Heart Center Freiburg Bad Krozingen, University of Freiburg, Department of Cardiology and Angiology, Freiburg, Germany

  • C Juelch

    1   University Heart Center Freiburg Bad Krozingen, University of Freiburg, Department of Cardiology and Angiology, Freiburg, Germany

  • C B Olivier

    1   University Heart Center Freiburg Bad Krozingen, University of Freiburg, Department of Cardiology and Angiology, Freiburg, Germany

  • D Duerschmied

    3   University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Mannheim, Germany
    4   European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany

  • D Bettinger

    2   University Hospital Freiburg, Faculty of Medicine, University of Freiburg, Department of Medicine II, Freiburg, Germany

  • K Krauel

    3   University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Mannheim, Germany
    1   University Heart Center Freiburg Bad Krozingen, University of Freiburg, Department of Cardiology and Angiology, Freiburg, Germany
Further Information
Also available at
 
 

Introduction: In patients with decompensated liver cirrhosis (LC), platelet aggregation is reduced in both whole blood (WB) and platelet-rich plasma (PRP) [1]. This study aimed to analyze platelet function and plasma factors in a larger cohort of decompensated LC patients.

Method: Platelet aggregation was assessed in response to thrombin receptor activating peptide 6 (TRAP-6), adenosine diphosphate (ADP) and arachidonic acid (AA) using whole blood impedance aggregometry (WBIA, expressed as area under the curve) and light transmission aggregometry (LTA, expressed as maximal aggregation in%). Fibrinogen and von Willebrand factor (VWF) binding to platelets was measured in response to the direct protein kinase C activator phorbol 12-myristate 13-acetate in a WB assay using flow cytometry and determined as geometric mean fluorescence intensity. In a subset of LC patients, we also performed flow cytometric analyses with washed platelets (WP). As a proof-of-principle, WP from healthy subjects were preincubated with plasma from LC patients or healthy controls and platelet aggregation was assessed by LTA. Platelet factor 4 (PF4) and serotonin plasma levels in ng/mL were determined by enzyme-linked immunosorbent assay.

Results: We confirmed impaired platelet aggregation responses in LC patients (n=37) compared with healthy controls (n=16) by WBIA (TRAP 79.5±34.1 vs. 122.9±20.8, P<0.0001; ADP 49.5±25.1 vs. 84.4±18.7, P<0.0001; AA 59.3±29.2 vs. 94.4±15.2, P<0.0001) and LTA (TRAP 76.2±16.1 vs. 86.2±13.2, P<0.05; ADP 62.5±23.0 vs. 84.3±15.5, P<0.01; AA 50.8±27.5 vs. 80.4±14.1, P<0.0001). Notably, fibrinogen (498.3±230.0 vs. 888.8±335.9, P<0.0001) and VWF (115.7±50.2 vs. 248.0±48.1, P<0.0001) binding to platelets were lower in LC patients (n=34) than in healthy controls (n=15) using WB. Low responses could not be explained by the pre-activation of platelets with similar PF4 (174.8±106.8 vs. 155.8±103.2, P=0.4689) or even lower serotonin (15.1±11.9 vs. 26.2±10.9, P<0.0001) plasma levels in LC patients (n=37) vs. healthy controls (n=16). However, binding of fibrinogen (470.8±189.5 vs. 1080.0±336.8, P<0.01) and VWF (97.3±28.5 vs. 306.4±117.0, P<0.001) to platelets improved in WP from LC patients (WB vs. WP, n=10). Finally, reduced platelet aggregation could be induced in WP from healthy donors which were preincubated with LC patient plasma (TRAP 66.8±8.3 vs. 82.6±7.1, P<0.05; ADP 23.0±7.7 vs. 72.6±6.9, P<0.001; AA 29.2±26.0 vs. 79.8±8.3, P<0.05 vs. control plasma, n=5).

Conclusion: Plasma components related to decompensated LC might hinder platelet aggregation responses by disturbing fibrinogen and VWF binding. Further investigations are needed to identify the plasma factor(s) involved in this inhibitory process.


 

Conflict of Interest:

The authors declare no conflict of interest.

  • References

  • 1 Nassar A, Huber JP, Stallmann D, Sharipova D, Hamad MA, Schultheiss M, Thimme R, Duerschmied D, Scharf RE, Bettinger D, Krauel K.. Decreased Platelet Aggregation in Patients with Decompensated Liver Cirrhosis and TIPS Implantation. Biomedicines 2023; 11 (07) 2057
    CrossrefPubMedSearch in Google Scholar

Publication History

Article published online:
13 February 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

  • References

  • 1 Nassar A, Huber JP, Stallmann D, Sharipova D, Hamad MA, Schultheiss M, Thimme R, Duerschmied D, Scharf RE, Bettinger D, Krauel K.. Decreased Platelet Aggregation in Patients with Decompensated Liver Cirrhosis and TIPS Implantation. Biomedicines 2023; 11 (07) 2057
    CrossrefPubMedSearch in Google Scholar