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
Abstract
BACKGROUND

Hemostasis of patients suffering from liver cirrhosis is challenging due to both, pro- and anticoagulatory disorders leading to hemostatic alterations with distinct abnormalities of coagulation. Pathological changes in conventional coagulation analysis and platelet count are common manifestations of decreased liver synthesis of coagulation factors and reduced platelet count in these patients. However, conventional coagulation analysis and platelet count do not reflect in-vivo coagulation status or platelet function. The purpose of this present observational study was therefore to assess the haemostatic profile including plasmatic coagulation using thrombelastometry and impedance aggregometry for platelet function in patients suffering from liver cirrhosis.

AIM

To assess the hemostatic profile of cirrhotic patients according to model for end-stage liver disease (MELD) score.

METHODS

Our study included both in- and outpatients suffering from liver cirrhosis attending the out- and inpatient care of the department of hepatology. Demographic and biochemical data as well as medical history including cause of liver cirrhosis, end stage kidney failure and medication with anticoagulants were recorded. To assess the hemostatic profile, platelet function was analyzed by multiple electrode aggregometry (MEA) using Multiplate® (ADP-, ASPI- and TRAP-test) and thrombelastometry using ROTEM® (EXTEM, INTEM, FIBTEM). Data were compared using Mann-Whitney U- or χ2-test. Spearman correlation was performed to analyze the association between MELD Score and results of thrombelastometry and MEA.

RESULTS

A total of 68 patients attending the out- and inpatient care suffering from liver cirrhosis were screened. Of these, 50 patients were included and assigned to groups according to MELD score 6 to 11 (n = 25) or ≥ 17 (n = 25). Baseline patient characteristics revealed significant differences for MELD score (8 vs 22, P < 0.0001) and underlying laboratory parameters (international normalized ratio, bilirubine, creatinine) as well as fibrinogen level (275 mg/dL vs 209 mg/dL, P = 0.006) and aPTT (30 s vs 35 s, P = 0.047). MEA showed a moderately impaired platelet function (medians: AUCADP = 43U, AUCASPI = 71U, AUCTRAP = 92U) but no significant differences between both groups. Thrombelastometry using ROTEM® (EXTEM, INTEM, FIBTEM) revealed values within normal range in both groups. No significant correlation was observed between MELD score and results of MEA/thrombelastometry.

CONCLUSION

Our data demonstrate a partially impaired hemostatic profile in liver cirrhosis patients unrelated to MELD score. An individual assessment of a potential coagulopathy should therefore be considered.

Keywords: Liver cirrhosis; Model for end-stage liver disease; Coagulopathy; Multiple electrode aggregometry; Thrombelastometry; Hemostasis

Core tip: The results of our study show a moderately decreased platelet aggregation but no substantial impairment of the maximum clot firmness considering thrombelastometric results. Correlation analysis indicated that impedance aggregometric and thrombelastometric results did not correlate with model for end-stage liver disease score. 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. Rather, an individual assessment of a potential coagulopathy in patients with advanced disease is reasonable.