Resistance to thrombomodulin correlates with liver stiffness in chronic liver disease a prospective single-center cohort study. Issue 207 (November 2021)

• Record Type: Journal Article
• Authors: Brodard, Justine; Calzavarini, Sara; Quarroz, Claudia; Berzigotti, Annalisa; De Gottardi, Andrea; Angelillo-Scherrer, Anne
• Is Part Of: Thrombosis research. Issue 207(2021)
• Page Start: 40
• Page End: 49
• Publication Date: 2021-11
• Subjects: AIH autoimmune hepatitis -- ALD alcoholic liver disease -- ALP alkaline phosphatase -- APC activated protein C -- AST aspartate transaminase alanine transaminase -- CAT calibrated automated assay -- CLD chronic liver disease -- ETP endogenous thrombin potential -- HBV hepatitis B virus -- HCV hepatitis C virus -- HFE hereditary hemochromatosis -- INR international normalized ratio -- LSM liver stiffness measurement -- NAFL non-alcoholic fatty liver -- PBC primary biliary cholangitis -- PFP platelets frozen plasma -- PPP platelets poor plasma -- PT prothrombin time -- STG ST Genesia® Thrombin generation system -- STG-BLS ST Genesia® Thrombin generation system BleedScreen -- STG-TS ST Genesia® Thrombin generation system ThromboScreen -- TF tissue factor -- TG thrombin generation -- TM thrombomodulin; Chronic liver disease -- Blood coagulation -- Thrombin generation -- Thrombomodulin resistance -- Liver stiffness; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2021.09.007
• Languages: English
• ISSNs: 0049-3848

Abstract

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. Highlights: ST Genesia® is a new automated instrument that may be a suitable routine coagulation laboratory instrument for the measurement of thrombin generation parameters in patients with chronic liver disease. We showed that high liver stiffness measurements identify a procoagulant phenotype in these patients, including thombomodulin resistance. Liver stiffness showed correlation with both ST Genesia® and calibrated automated thrombogram assays. ST Genesia® assay may be better than calibrated automated thrombogram assay as more of its parameters correlate with liver stiffness in patients with chronic liver disease. Liver stiffness measurements ≥21 kPa identify a procoagulant phenotype in the studied cohort, including thombomodulin resistance.