Liver Dysfunction Biomarkers Correlate with a Prothrombotic and Not with a Prohemorrhagic Hemostatic Profile in Cirrhotic Patients

M.G. Zermatten¹, M. Fraga², D. Bertaggia Calderara¹, A. Aliotta¹, D. Moradpour², L. Alberio¹

¹Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Division of Hematology and Central Hematology Laboratory, Lausanne, Switzerland, ²Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Division of Gastroenterology and Hepatology, Lausanne, Switzerland

Abstract Number: PB0354

Meeting: ISTH 2020 Congress

Theme: Coagulation and Natural Anticoagulants » Hemostasis and Organ Dysfunction

Background: Cirrhotic patients were demonstrated to be at increased thrombotic risk in studies using Calibrated Automated Thrombogram (CAT), a non-standardised/non-fully automated thrombin generation (TG) assay. However, due to the high analytical variability, these studies exhibit discrepancies. Moreover, different liver cirrhosis (LC) severity biomarkers are used to assess the bleeding risk of LC-patients.

Aims: We aimed to perform a larger study using automated/standardised TG-assays in order to:
i) obtain robust data on LC-severity and TG; and
ii) investigate relationships between LC-severity biomarkers and TG, questioning their adequacy for bleeding risk-assessment.

Methods: We performed a prospective single-centre study (n=200). TG was measured without/with thrombomodulin (TM) using ST Genesia® (Stago, Asnières-sur-Seine, France). We analysed the relationship between TG-parameters without TM and TM-mediated inhibition, and MELD-score/PT/INR/aPTT/FV-activity/albumin/total bilirubin.

Results: Without TM, the endogenous thrombin potential (ETP) and the peak height were slightly decreased and the velocity index (VI) was increased in LC-patients versus healthy donors (p=0.046/0.031/< 0.0001). The VI increased from Child A to B-patients (p=0.004). With TM, the ETP and the peak height were increased in LC-patients versus healthy donors (p=0.0002/0.003) and in Child B versus A-patients (p=0.009/0.028). This resulted in a decreased TM-mediated inhibition in LC-patients versus healthy donors and in Child B versus A-patients (p< 0.0001).
The TM-mediated inhibition showed a direct relationship with PT/FV-activity/albumin and an inverse relationship with INR/aPTT/bilirubin/MELD-score (R²=0.448/0.483/0.310/0.389/0.326/0.295/0.250, respectively). Relationships between VI without TM and LC-severity biomarkers were coherent with results of TM-mediated inhibition (R²=0.141/0.315/0.124/0.068/0.110/0.119, respectively).

Conclusions: Using an automated/standardised TG-assay (without and with TM), we documented that LC-patients are prothrombotic. We also confirmed a decreased TM-mediated inhibition, which is due to an acquired protein C-resistance. We demonstrated an increasing prothrombotic profile with increasing biomarker-disturbances in LC-patients. Therefore, these parameters should not be used for estimating bleeding risk in LC-patients. Alternative biomarkers for bleeding risk-assessment in LC-patients need to be developed.

To cite this abstract in AMA style:

Zermatten MG, Fraga M, Bertaggia Calderara D, Aliotta A, Moradpour D, Alberio L. Liver Dysfunction Biomarkers Correlate with a Prothrombotic and Not with a Prohemorrhagic Hemostatic Profile in Cirrhotic Patients [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/liver-dysfunction-biomarkers-correlate-with-a-prothrombotic-and-not-with-a-prohemorrhagic-hemostatic-profile-in-cirrhotic-patients/. Accessed December 6, 2023.

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