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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2016; 22(6): 2005-2023
Published online Feb 14, 2016. doi: 10.3748/wjg.v22.i6.2005
Coagulopathy and transfusion therapy in pediatric liver transplantation
Mirco Nacoti, Davide Corbella, Francesco Fazzi, Francesca Rapido, Ezio Bonanomi
Mirco Nacoti, Francesco Fazzi, Ezio Bonanomi, Pediatric Intensive Care Unit, Ospedale Papa Giovanni XXIII Piazza OMS, 24127 Bergamo, Italy
Davide Corbella, Department of Anesthesia, Ospedale Papa Giovanni XXIII, 24127 Bergamo, Italy
Francesca Rapido, Faculty of Medicine, Università Statale di Milano, 20122 Milano, Italy
Author contributions: Nacoti M, Corbella D and Fazzi F reviewed the literature and drafted the manuscript; Rapido F and Bonanomi E revised and approved the final version.
Conflict-of-interest statement: The authors have no conflicts of interest to report.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Mirco Nacoti, MD, Pediatric Intensive Care Unit, Ospedale Papa Giovanni XXIII Piazza OMS, Organizzazione Mondiale della Sanità 1, 24127 Bergamo, Italy. mnacoti@hpg23.it
Telephone: +39-35-2675150 Fax: +39-35-2674989
Received: May 30, 2015
Peer-review started: June 4, 2015
First decision: October 14, 2015
Revised: November 23, 2015
Accepted: December 30, 2015
Article in press: December 30, 2015
Published online: February 14, 2016
Processing time: 238 Days and 16.2 Hours
Abstract

Bleeding and coagulopathy are critical issues complicating pediatric liver transplantation and contributing to morbidity and mortality in the cirrhotic child. The complexity of coagulopathy in the pediatric patient is illustrated by the interaction between three basic models. The first model, “developmental hemostasis”, demonstrates how a different balance between pro- and anticoagulation factors leads to a normal hemostatic capacity in the pediatric patient at various ages. The second, the “cell based model of coagulation”, takes into account the interaction between plasma proteins and cells. In the last, the concept of “rebalanced coagulation” highlights how the reduction of both pro- and anticoagulation factors leads to a normal, although unstable, coagulation profile. This new concept has led to the development of novel techniques used to analyze the coagulation capacity of whole blood for all patients. For example, viscoelastic methodologies are increasingly used on adult patients to test hemostatic capacity and to guide transfusion protocols. However, results are often confounding or have limited impact on morbidity and mortality. Moreover, data from pediatric patients remain inadequate. In addition, several interventions have been proposed to limit blood loss during transplantation, including the use of antifibrinolytic drugs and surgical techniques, such as the piggyback and lowering the central venous pressure during the hepatic dissection phase. The rationale for the use of these interventions is quite solid and has led to their incorporation into clinical practice; yet few of them have been rigorously tested in adults, let alone in children. Finally, the postoperative period in pediatric cohorts of patients has been characterized by an enhanced risk of hepatic vessel thrombosis. Thrombosis in fact remains the primary cause of early graft failure and re-transplantation within the first 30 d following surgery, and it occurs despite prolongation of standard coagulation assays. Data, however, are currently lacking regarding the use of anti-aggregation/anticoagulation therapies and how to best monitor for thrombosis in the early postoperative period in pediatric patients. Therefore, further studies are necessary to elucidate the interaction between the development of the coagulation system and cirrhosis in children. Moreover, strategies to optimize blood transfusion and anticoagulation must be tested specifically in pediatric patients. In conclusion, data from the adult world can be translated with difficulty into the pediatric field as indication for transplantation, baseline pathologies and levels of pro- and anticoagulation factors are not comparable between the two populations.

Keywords: Children; Coagulation; Thrombosis; Liver disease; Transfusion; Transplantation; Point of care coagulation

Core tip: In the last two decades, extensive investigation of abnormalities in hemostasis in adult cirrhotic patients and improvements in both surgical and anesthetic management has enhanced outcome following liver transplantation. Unfortunately, such knowledge cannot be directly applied to pediatric patients, as major differences exist between adults and children undergoing liver transplantation. In this review, we discuss the pattern of hemostatic abnormalities in children with end-stage liver disease, point-of-care coagulation monitoring, and clinical strategies designed to reduce bleeding and thrombosis in pediatric liver transplantation. In conclusion, we propose a prioritized research agenda for this pediatric subspecialty.