Clinical Trials Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2020; 26(17): 2097-2110
Published online May 7, 2020. doi: 10.3748/wjg.v26.i17.2097
Assessment of hemostatic profile in patients with mild to advanced liver cirrhosis
Elisabeth Hannah Adam, Madara Möhlmann, Eva Herrmann, Sonia Schneider, Kai Zacharowski, Stefan Zeuzem, Christian Friedrich Weber, Nina Weiler
Elisabeth Hannah Adam, Madara Möhlmann, Sonia Schneider, Kai Zacharowski, Christian Friedrich Weber, Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt 60590, Germany
Eva Herrmann, Department of Biostatistics and mathematical modeling, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt 60590, Germany
Stefan Zeuzem, Nina Weiler, Department of Internal Medicine, Division of Gastroenterology and Hepatology, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt 60590, Germany
Christian Friedrich Weber, Department of Anaesthesiology, Intensive Care Medicine and Emergency Medicine, Asklepios Clinics Hamburg, Hamburg 22043, Germany
Author contributions: Adam EH, Schneider S, Weber CF and Weiler N contributed to study conception and design; Adam EH, Möhlmann M, Schneider S, Herrmann E, Weber CF and Weiler N contributed to data acquisition, data analysis and interpretation, and writing of article; Adam EH, Möhlmann M, Herrmann E, Zacharowski K, Zeuzem S, Weber CF and Weiler N contributed to editing, reviewing and final approval of article.
Institutional review board statement: Approval of the local ethics committee of the University Hospital Frankfurt was obtained before study was performed (reference #195/17). Written informed consent was obtained from all patients. The study was performed in accordance with the Declaration of Helsinki. Patient care and study conduct complied with good clinical practice.
Clinical trial registration statement: The study was registered to the ClinicalTrials.gov Protocol Registration and Results System (NCT04265508).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: EHA received honoraria for scientific lectures from CSL Behring and Fresenius Kabi GmbH. KZ department is receiving unrestricted educational grants from B. Braun Melsungen AG, Fresenius Kabi GmbH, CSL Behring GmbH and Vifor Pharma GmbH. In the past 3 years, KZ has received honoraria or travel support for consulting or lecturing from the following companies: Abbott GmbH &Co KG, Aesculap Akademie GmbH, AQAI GmbH, Astellas Pharma GmbH, Astra Zeneca GmbH, Aventis Pharma GmbH, B. Braun Melsungen AG, Baxter Deutschland GmbH, Biosyn GmbH, Biotest AG, Bristol-Myers Squibb GmbH, CSL Behring GmbH, Dr. F. Köhler Chemie GmbH, Dräger Medical GmbH, Essex Pharma GmbH, Fresenius Kabi GmbH, Fresenius Medical Care, Gambro Hospal GmbH, Gilead, GlaxoSmithKline GmbH, Grünenthal GmbH, Hamilton Medical AG, HCCM Consulting GmbH, Heinen + Löwenstein GmbH, Janssen-Cilag GmbH, med Update GmbH, Medivance EU B.V., MSD Sharp & Dohme GmbH, Novartis Pharma GmbH, Novo Nordisk Pharma GmbH, P. J. Dahlhausen & Co. GmbH, Pfizer Pharma GmbH, Pulsion Medical Systems S.E., Siemens Healthcare, Teflex Medical GmbH, Teva GmbH, TopMedMedizintechnik GmbH, Verathon Medical, ViforPharma GmbH. SZ received honoraria for consultancy and/or scientific lectures from Abbvie, Gilead, Intercept, Janssen, Merck/MSD. CW received honoraria for scientific lectures from CSL Behring, Haemonetics, Biotest, Verum Diagnostica and Roche. NW received speaker’s fees from Astellas and Novartis as well as travel support from Abbvie, Astellas and Novartis.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Elisabeth Hannah Adam, MD, Attending Doctor, Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe-University Frankfurt, Theodor-Stern Kai 7, Frankfurt 60590, Germany. elisabeth.adam@kgu.de
Received: February 11, 2020
Peer-review started: February 11, 2020
First decision: February 27, 2020
Revised: March 26, 2020
Accepted: April 24, 2020
Article in press: April 24, 2020
Published online: May 7, 2020
Processing time: 86 Days and 1 Hours
ARTICLE HIGHLIGHTS
Research background

Liver cirrhosis leads to hemostatic alterations. Despite laboratory findings suggesting a coagulopathy, these do not reflect bleeding events in cirrhosis patients. Routine diagnostic tests display relevant limitations, as they may not provide accurate information on the hemostatic status; they cannot predict bleeding risk and may therefore not provide clinically relevant information.

Research motivation

Viscoelastic tests are global tests of coagulation, which assess the viscoelastic properties of blood. The aim of the present study was to assess the haemostatic profile of patients suffering from mild to advanced liver cirrhosis, including platelet function testing and viscoelastic testing. Results originating from these tests may close the gap in testing patients with liver cirrhosis for

Research objectives

The objective was to study the hemostatic profile of patients with liver cirrhosis and to correlate results from both tests with the severity of liver cirrhosis.

Research methods

Platelet function was measured by multiple electrode aggregometry using the multiplate analyzer 15 min after blood draw and after activation with commercially available standard reagents. Blood samples were analyzed at 37 °C. Thrombelastometric assays were performed 15 min after blood draw. Blood samples were analyzed at 37 °C using ROTEM delta analyzer. A runtime of 60 min was applied and regular quality control tests and ROTEM tests were run in accordance with the manufacturer’s instructions. Data comparisons of patient characteristics and results of multiple electrode aggregometry (MEA) and thrombelastometry were made using Mann-Whitney U- or Fisher’s exact-test, where applicable. To correlate parameters from MEA and thrombelastometry with other parameters, Spearman rank correlation analysis fitting a linear regression line were performed.

Research results

Our prospective study in 50 patients with suffering from mild to advanced liver cirrhosis showed that the hemostatic profile assessed by viscoelastic tests is not associated with the severity of liver cirrhosis according to model for end-stage liver disease (MELD) score and ranged from normal to hypocoagulable state. In detail, comparing the observed MEA results to severity of liver cirrhosis, those patients who displayed abnormal results below the reference range showed mostly mild thrombopenia especially in the group of advanced liver cirrhosis.

Research conclusions

Our data demonstrate a partially impaired hemostatic profile of both platelet function and plasmatic coagulation in cirrhotic patients, but no correlation of impairment with the severity of liver cirrhosis. Therefore, the hemostatic potential or a hemostatic therapy should not be judged by MELD score alone but rather by an individual and patient-specific assessment. Further, our data indicate that a potential coagulopathy in advanced liver cirrhosis may not be reflected by thrombelastometry or multiple electrode aggregometry as the underlying mechanisms may be beyond the platelet function of hemostasis. In clinical practice, viscoelastic testing may prove to be an asset in the assessment of hemostatic profiling of patients suffering from liver cirrhosis.

Research perspectives

Ultimately, further tests need to be developed to further reflect/identify patients with an impaired hemostatic potential.