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  3. Resistance to thrombomodulin correlates with liver stiffness in chronic liver disease a prospective single-center cohort study.

Resistance to thrombomodulin correlates with liver stiffness in chronic liver disease a prospective single-center cohort study.

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DOI
10.48350/159486
Publisher DOI
10.1016/j.thromres.2021.09.007
PubMed ID
34536665
Abstract
INTRODUCTION

Chronic liver disease (CLD) is characterized by changes in haemostasis, embracing both hypo- and hypercoagulability. Global hemostatic tests such as thrombin generation assays evaluate the hemostatic balance, to better assess bleeding and thrombotic risks. In addition, procoagulant state in patients with CLD has been demonstrated using modified thrombin generation assays with thrombomodulin, a cofactor for protein C activation. In this study, we prospectively determined thrombin generation and thrombomodulin resistance in patients with CLD staged with liver stiffness measurement (LSM), using both the fully automated analyzer ST Genesia® Thrombin Generation System (STG) and the calibrated automated thrombogram assay (CAT).

MATERIALS AND METHODS

Demographic, clinical and laboratory characteristics, and blood samples were collected from 65 patients with CLD. Liver stiffness was measured by transient elastography, and thrombin generation and thrombomodulin resistance, by STG and CAT.

RESULTS

Patients were separated based on LSM of <21 and ≥21 kilopascals (kPa). The propagation rate of thrombin generation was higher in patients with LSM ≥21 kPa and the thrombin generation rate increased as LSM increased. In addition, thrombomodulin resistance assessed by STG and CAT was higher in patients with LSM ≥21 kPa. However, ETP inhibition by activated protein C was comparable in patients with LSM <21 and ≥21 kPa. Finally, LSM correlated with most thrombin generation parameters.

CONCLUSION

The STG automated system may have value in the assessment of patients with chronic liver disease in the routine coagulation laboratory. LSM ≥21 kPa identify a procoagulant phenotype in these patients, including thrombomodulin resistance.
Date Issued
2021-11
Publication Type
Article
Subject(s)
600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services
Subjects
Blood coagulation Chronic liver disease Liver stiffness Thrombin generation Thrombomodulin resistance
Language(s)
en
Author(s)
Brodard, Justine  
Universitätsklinik für Hämatologie und Hämatologisches Zentrallabor  
Department for BioMedical Research, Forschungsgruppe Hämatologie (Erwachsene)  
Calzavarini, Sara  
Department for BioMedical Research, Forschungsgruppe Hämatologie (Erwachsene)  
Universitätsklinik für Hämatologie und Hämatologisches Zentrallabor  
Quarroz, Claudia  
Department for BioMedical Research, Forschungsgruppe Hämatologie (Erwachsene)  
Department for BioMedical Research (DBMR)  
Berzigotti, Annalisa  orcid-logo
Universitätsklinik für Viszerale Chirurgie und Medizin, Hepatologie  
De Gottardi, Andrea  
Department for BioMedical Research, Hepatologie Forschung  
Universitätsklinik für Viszerale Chirurgie und Medizin, Hepatologie  
Angelillo, Anne  
Universitätsklinik für Hämatologie und Hämatologisches Zentrallabor  
Department for BioMedical Research, Forschungsgruppe Hämatologie (Erwachsene)  
Additional Credits
Universitätsklinik für Viszerale Chirurgie und Medizin, Hepatologie  
Department for BioMedical Research, Hepatologie Forschung  
Universitätsklinik für Hämatologie und Hämatologisches Zentrallabor  
Department for BioMedical Research, Forschungsgruppe Hämatologie (Erwachsene)  
Department for BioMedical Research (DBMR)  
Journal
Thrombosis research
Publisher
Elsevier
ISSN
0049-3848
Access(Rights)
open.access
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