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

Brodard, Justine; Calzavarini, Sara; Quarroz, Claudia; Berzigotti, Annalisa; De Gottardi, Andrea; Angelillo-Scherrer, Anne (2021). Resistance to thrombomodulin correlates with liver stiffness in chronic liver disease a prospective single-center cohort study. Thrombosis research, 207, pp. 40-49. Elsevier 10.1016/j.thromres.2021.09.007

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene)
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)

UniBE Contributor:

Brodard, Justine; Calzavarini, Sara; Quarroz, Claudia; Berzigotti, Annalisa; De Gottardi, Andrea and Angelillo, Anne

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

0049-3848

Publisher:

Elsevier

Language:

English

Submitter:

Pierrette Durand Lüthi

Date Deposited:

06 Oct 2021 14:22

Last Modified:

15 Nov 2021 00:14

Publisher DOI:

10.1016/j.thromres.2021.09.007

PubMed ID:

34536665

Uncontrolled Keywords:

Blood coagulation Chronic liver disease Liver stiffness Thrombin generation Thrombomodulin resistance

BORIS DOI:

10.48350/159486

URI:

https://boris.unibe.ch/id/eprint/159486

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