Download PDF
Thromb Haemost 2020; 120(09): 1240-1247
DOI: 10.1055/s-0040-1713752
Coagulation and Fibrinolysis

In Vitro Evaluation of Pro- and Anticoagulant Drugs in Children with End-Stage Liver Disease Undergoing Liver Transplantation

Maureen J. M. Werner
1   Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
2   Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
,
Jelle Adelmeijer
2   Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
,
Vincent E. de Meijer
1   Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
,
Ruben H. J. de Kleine
1   Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
,
René Scheenstra
3   Department of Pediatric Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
,
Sander T. H. Bontemps
4   Department of Pediatric Intensive Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
,
Koen M. E. M. Reyntjens
5   Department of Anesthesiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
,
Jan B. F. Hulscher
6   Section of Pediatric Surgery, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
,
Robert J. Porte
1   Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
2   Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
,
Ton Lisman
1   Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
2   Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
› Author Affiliations Funding Research funding was obtained by the University Medical Center Groningen Transplantation Research Foundation, Groningen, the Netherlands.
› Further Information
Also available at
   Buy Article Permissions and Reprints
Zoom Image

Abstract

Background Pro- and anticoagulant drugs are commonly used in pediatric liver transplantation to prevent and treat thrombotic and bleeding complications. However, the combination of baseline hemostatic changes in children with liver disease and additional changes induced by transplantation makes this very challenging. This study aimed to analyze the efficacy of clinically available pro- and anticoagulant drugs in plasma from children undergoing liver transplantation.

Methods In vitro effects of pro- and anticoagulant drugs on thrombin generation capacity were tested in plasma samples of 20 children (≤ 16 years) with end-stage liver disease undergoing liver transplantation, and compared with 30 age-matched healthy controls.

Results Addition of pooled normal plasma had no effect in patients or controls, while 4-factor prothrombin complex concentrate increased thrombin generation in both patients and controls, with enhanced activity in patients. At start of transplantation, dabigatran and unfractionated heparin had a higher anticoagulant potency in patients, whereas 30 days after transplantation low molecular weight heparin was slightly less effective in patients. Effects of rivaroxaban were comparable between patients and controls.

Conclusion This study revealed important differences in efficacy of commonly used pro- and anticoagulant drugs in children with end-stage liver disease undergoing liver transplantation. Therefore, dose adjustments of these drugs may be required. The results of this study may be helpful in the development of urgently needed protocols for strategies to prevent and treat bleeding and thrombotic complications in pediatric liver transplantation.

Keywords

coagulation - hemostasis - liver transplantation - pro- and anticoagulant drugs - thrombosis

Supplementary Material



Publication History

Received: 26 March 2020

Accepted: 18 May 2020

Article published online:
06 July 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Stuttgart · New York