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Thrombin dynamics in children with liver disease or extrahepatic portal vein obstruction or shunt.

Authors
  • Beattie, William1
  • Kremers, Romy2
  • Magnusson, Maria3
  • Peters, Tessa2
  • de Laat, Bas2
  • Hardikar, Winita4
  • Monagle, Paul5
  • Ignjatovic, Vera6
  • 1 Murdoch Children's Research Institute, Parkville, Victoria, Australia. , (Australia)
  • 2 Synapse BV, Maastricht University, the Netherlands. , (Netherlands)
  • 3 Murdoch Children's Research Institute, Parkville, Victoria, Australia; MMK, Division of Clinical Chemistry and Coagulation & CLINTEC, Division of Paediatrics, Karolinska Institutet, Astrid Lindgren Children's Hospital, Karolinska University Hospital, SE-141 86 Stockholm, Sweden. , (Australia)
  • 4 Department of Gastroenterology, Royal Children's Hospital, Parkville, Victoria, Australia. , (Australia)
  • 5 Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, the University of Melbourne, Parkville, Victoria, Australia; Department of Clinical Haematology, Royal Children's Hospital, Parkville, Victoria, Australia. , (Australia)
  • 6 Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, the University of Melbourne, Parkville, Victoria, Australia. Electronic address: [email protected] , (Australia)
Type
Published Article
Journal
Thrombosis research
Publication Date
Feb 13, 2020
Volume
188
Pages
65–73
Identifiers
DOI: 10.1016/j.thromres.2020.02.008
PMID: 32087412
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Changes in the coagulation profile in children with liver disease and extrahepatic portal vein obstruction or shunt result in both bleeding and thrombosis. Routine coagulation tests do not accurately predict bleeding risk, as they are not sensitive to changes in anticoagulant factors. The thrombin generation assay could be suitable for describing the overall balance of coagulation in children with liver disease. This study aims to characterise the mechanism of thrombin generation in this population, focusing on prothrombin conversion and thrombin inhibition. Patients were categorised as: severe (paediatric end stage liver disease score > 15) and mild disease, or portal vein obstruction or shunt. Age and gender matched healthy controls were used. The thrombin generation assay was performed in plasma samples from patients and controls with and without exogenous thrombomodulin and the results were further analysed with the computational thrombin dynamics method. A total of 42 patients (severe, n = 5; mild, n = 29, obstruction/shunt, n = 8) and 20 controls were included in this study. The total prothrombin conversion, thrombin-antithrombin formation and the thrombin decay capacity, in the presence and absence of thrombomodulin were reduced in children with severe liver disease. The rate of prothrombin conversion was increased and thrombin decay capacity was decreased in patients with portal vein obstruction or shunt compared to controls. This study demonstrates changes in the mechanism in thrombin generation seen in severe chronic liver disease. The changes vary in parenchymal versus non parenchymal liver disease and further study assessing the clinical significance of these variations in mechanism is required. Copyright © 2020 Elsevier Ltd. All rights reserved.

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