Biomarkers of liver dysfunction correlate with a prothrombotic and not with a prohaemorrhagic profile in patients with cirrhosis

Zermatten, Maxime G.; Fraga, Montserrat; Calderara, Debora Bertaggia; Aliotta, Alessandro; Moradpour, Darius; Alberio, Lorenzo

doi:10.1016/j.jhepr.2020.100120

Cited by 21 publications

(20 citation statements)

References 43 publications

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“…This parameter has a decreased tendency with increasing severity of cirrhosis depending on the Child–Pugh score. In this study, they demonstrate that patients with liver cirrhosis have an increasing prothrombotic profile correlating with worsening alteration of liver dysfunction biomarkers [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Thrombin Generation in Chronic Liver Diseases—A Pilot Study

Vecerzan

Olteanu²,

Maniu

et al. 2021

Healthcare

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The knowledge about coagulation disorders in patients with chronic liver disease changed in the last decade. The aim of this study was to analyze the parameters of thrombin generation in patients with chronic liver disease, as they are the most appropriate biomarkers to explore coagulation. (1) Background: The knowledge about coagulation disorders in patients with chronic liver disease changed in the last decade. The study of thrombin generation in patients with chronic liver disease provides a much more accurate assessment of the coagulation cascade; (2) Methods: This study is a prospective observational pilot study on hospitalized patients with chronic liver diseases that analyzed thrombin generation performed from their platelet-poor plasma versus that of control subjects. We analyzed a group of 59 patients with chronic liver disease and 62 control subjects; (3) Results: Thrombin generation was lower in hepatitis and cirrhosis patients compared to controls and decreases as the disease progressed. Lag time was higher in ethanolic etiology compared to the control group. Peak thrombin and endogenous thrombin potential were shorter in all etiologies when compared to the control group. The velocity index was significantly lower in HCV hepatopathies, ethanolic, and mixed etiology when compared with normal individuals; (4) Conclusions: Given the variability of thrombin generation in patients with chronic liver disease, its assay could serve to identify patients with high thrombotic and hemorrhagic risk and establish personalized conduct toward them.

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Section: Discussionmentioning

confidence: 99%

Thrombin Generation in Chronic Liver Diseases—A Pilot Study

Vecerzan

Olteanu²,

Maniu

et al. 2021

Healthcare

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“…The measurement is performed in the presence of defined concentrations of tissue factor (low, normal or high), allowing the modulation of the sensitivity of the test (e.g., high concentration of tissue factor will make the test less sensitive to the intrinsic pathway). Thrombomodulin-modified TGA is a novel variant of the classical TGA, which allows the highlighting of the role of the protein C system in downregulating the coagulation process [ 223 ]. This might be of interest for investigating platelet-dependent TG because it has been demonstrated that platelet-derived activated coagulation factor Va (FVa) bound on the surface of procoagulant platelets is protected from inactivation catalysed by activated protein C [ 224 ].…”

Section: Procoagulant Plateletsmentioning

confidence: 99%

Thrombocytopathies: Not Just Aggregation Defects—The Clinical Relevance of Procoagulant Platelets

Aliotta

Calderara

Zermatten

et al. 2021

JCM

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Platelets are active key players in haemostasis. Qualitative platelet dysfunctions result in thrombocytopathies variously characterized by defects of their adhesive and procoagulant activation endpoints. In this review, we summarize the traditional platelet defects in adhesion, secretion, and aggregation. In addition, we review the current knowledge about procoagulant platelets, focusing on their role in bleeding or thrombotic pathologies and their pharmaceutical modulation. Procoagulant activity is an important feature of platelet activation, which should be specifically evaluated during the investigation of a suspected thrombocytopathy.

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“…Conventional coagulation tests do not reflect the hemostatic balance in patients with CLD [1]. In patients with CLD, TG and TM-modified TG are currently considered a more accurate measure of the in vivo coagulation, because it can assess both pro-and anticoagulant forces [15,[19][20][21][22][38][39][40]. There is evidence of a procoagulant imbalance in patients with CLD.…”

Section: Discussionmentioning

confidence: 99%

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

Brodard

Calzavarini

Quarroz

et al. 2021

Thrombosis Research

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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.

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Biomarkers of liver dysfunction correlate with a prothrombotic and not with a prohaemorrhagic profile in patients with cirrhosis

Cited by 21 publications

References 43 publications

Thrombin Generation in Chronic Liver Diseases—A Pilot Study

Thrombin Generation in Chronic Liver Diseases—A Pilot Study

Thrombocytopathies: Not Just Aggregation Defects—The Clinical Relevance of Procoagulant Platelets

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

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