Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Apr 27, 2019; 11(4): 379-390
Published online Apr 27, 2019. doi: 10.4254/wjh.v11.i4.379
Effectiveness of venous thromboembolism prophylaxis in patients with liver disease
Jason Yerke, Seth R. Bauer, Stephanie Bass, Heather Torbic, Michael Militello, Erin Roach, Ibrahim Hanouneh, Sarah Welch
Jason Yerke, Seth R. Bauer, Stephanie Bass, Heather Torbic, Michael Militello, Sarah Welch, Department of Pharmacy, Cleveland Clinic, Cleveland, OH 44195, United States
Erin Roach, Department of Pharmacy, Carolinas Medical Center, Charlotte, NC 28203, United States
Ibrahim Hanouneh, Department of Gastroenterology, Mayo Clinic, Rochester, MN 55905, United States
Author contributions: Yerke J, Welch S, Bauer S, Bass S, Torbic H and Militello M conceived the research study design; Yerke J collected data; Yerke J and Welch S interpreted data; Yerke J drafted the manuscript; Yerke J, Welch S, Bauer S, Bass S, Torbic H, Militello M, Hanouneh I and Roach E critically revised the manuscript.
Supported by: Cleveland Clinic Department of Pharmacy.
Institutional review board statement: The study was reviewed and approved by the Cleveland Clinic Foundation Institutional Review Board.
Conflict-of-interest statement: Dr. Hanouneh reports personal fees from Merck and Co., personal fees from Dova Pharmaceuticals, personal fees from Gilead Sciences, Inc., outside the submitted work; all other authors report no potential conflicts of interest.
STROBE statement: The authors have read the STROBE statement checklist of items, and the manuscript was prepared and revised according to the STROBE statement checklist of items.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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:
Corresponding author: Jason Yerke, PharmD, Pharmacist, Department of Pharmacy, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, United States.
Telephone: +1-216-4425553
Received: January 10, 2019
Peer-review started: January 10, 2019
First decision: March 5, 2019
Revised: March 22, 2019
Accepted: April 8, 2019
Article in press: April 8, 2019
Published online: April 27, 2019
Research background

Hepatic cirrhosis has historically been considered a coagulopathic disease, as traditional measurements of coagulation are often deranged. However, more recent literature suggests an altered coagulation cascade that may be tipped toward thrombosis or bleeding based on acute insults. Major venous thromboembolism (VTE) prophylaxis guidelines currently make no recommendation on whether to provide pharmacological prophylaxis to hospitalized cirrhotic patients. This study sought to improve on previously published retrospective data that has studied this topic, and attempted to provide data about whether pharmacological prophylaxis provides net clinical benefit or causes harm in a cirrhotic population.

Research motivation

The main problem that this study attempted to solve is whether pharmacological VTE prophylaxis prevents thrombotic events in patients with cirrhosis without causing a significant additional bleeding burden. Solving this problem could provide clarity in regards to the optimal strategy to prevent thrombotic events in cirrhotic patients.

Research objectives

The main objective of this study was to determine whether pharmacological VTE prophylaxis was beneficial overall to cirrhotic patients. This was assessed using a composite outcome of incident VTE and incident major bleeding, as the authors considered either of the events included in the composite outcome to be similarly detrimental to a patient. We feel that this study evaluated the benefits of pharmacological prophylaxis to the best of the capabilities of a retrospective study, and showed no harm to patients receiving prophylactic anticoagulation. Our findings could be used to demonstrate that pharmacological prophylaxis is likely safe in a population such as ours, which could allow for a future prospective, randomized controlled trial to be completed in an ethical manner.

Research methods

This study was a retrospective, cohort trial of patients with cirrhosis that received or did not receive pharmacological VTE prophylaxis during a hospitalization for any indication. Cirrhosis and other baseline past medical history that may have contributed to bleeding or thrombosis were identified using ICD-9 codes. Incident major bleeding and incident VTE were identified using ICD-9 codes and verified in the patient’s medical record by reviewing relevant imaging reports and lab values. We attempted to balance the patient groups by performing propensity score matching, and to account for any additional imbalance through multivariable logistic regression.

Research results

Baseline characteristics were largely balanced when comparing groups. Our primary outcome (the composite of incident major bleeding or incident VTE) was found to occur significantly less frequently in the prophylaxis group than in the no prophylaxis group (5.1 vs 8.7%, P < 0.05), though this result was driven largely by a higher rate of major bleeding in the no prophylaxis group. This result was confirmed on multivariable analysis, as receipt of pharmacological prophylaxis was significantly associated with a lower odds of major bleeding (though no significant association with pharmacological prophylaxis was noted on multivariable analysis of VTE).

Research conclusions

The major finding of this study was that pharmacological VTE prophylaxis did not increase the incidence of major bleeding in a large cohort of hospitalized cirrhotic patients. This challenges the historical idea that pharmacological prophylaxis should be withheld from cirrhotic patients due to an increased bleeding risk, and is more in line with recent findings that while cirrhotic patients have an altered coagulation cascade, they are at risk for both thrombotic and bleeding complications depending on acute insults. This finding could be the impetus for a large, randomized controlled trial in this patient population that could better answer the question of whether prophylactic anticoagulation truly prevents incident thrombotic events in a cirrhotic population.

Research perspectives

We feel that the only way to definitively answer the question of whether pharmacological prophylaxis is effective in preventing incident thrombotic events in a cirrhotic population is through a randomized, controlled trial. However, we feel that the lack of an increase in bleeding complications observed in this study is significant, and should allow for the pursuit of such a study without significant concern for harming a cirrhotic population similar to ours by providing pharmacologic VTE prophylaxis.