Persisting thrombomodulin resistance at 3 months after liver transplantation in children with cirrhosis
Background: The coagulation cascade in pediatric cirrhotic patients appears rebalanced, similar to adults, with few true hemostasis-related bleeds or thromboembolic events before liver transplantation. Vascular thrombosis is an important post–liver transplantation complication. Few papers have addre...
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Elsevier
2025-02-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2475037925000330 |
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| author | Marie-Astrid van Dievoet Clara David Audrey Dieu Cedric Hermans Thierry Pirotte Jonathan Douxfils Ton Lisman Xavier Stephenne |
| author_facet | Marie-Astrid van Dievoet Clara David Audrey Dieu Cedric Hermans Thierry Pirotte Jonathan Douxfils Ton Lisman Xavier Stephenne |
| author_sort | Marie-Astrid van Dievoet |
| collection | DOAJ |
| description | Background: The coagulation cascade in pediatric cirrhotic patients appears rebalanced, similar to adults, with few true hemostasis-related bleeds or thromboembolic events before liver transplantation. Vascular thrombosis is an important post–liver transplantation complication. Few papers have addressed the recovery of the coagulation cascade after liver transplantation. Objectives: We aimed to assess the coagulation cascade, with both measurement of individual factors and a global hemostasis assay, before living donor liver transplantation and to investigate its recovery 3 months after transplantation, when liver function has normalized. Methods: From January 2022 to July 2023, pediatric cirrhotic patients were prospectively enrolled 1 day before liver transplantation. An age-matched control group was included for comparison. Routine hemostasis tests, levels of coagulation factors and natural anticoagulants, and thrombomodulin-modified thrombin generation were determined on automated coagulation analyzers at inclusion and 3 months after liver transplantation. Results: Twenty-seven pediatric patients with cirrhosis, primarily of cholestatic origin, and 10 controls were enrolled. Sixteen patients were sampled 3 months after liver transplantation. Pediatric end-stage liver disease scores ranged from −10 to 44. A rebalanced coagulation cascade was confirmed in cirrhotic children, indicated by a thrombomodulin-modified thrombin generation assay similar to controls, although with higher interpatient variability. Interestingly, 3 months posttransplant, coagulation was not completely normalized. In the majority of patients resistance to thrombomodulin persisted. Conclusion: This study confirmed a rebalanced coagulation system in pediatric cirrhotic patients before liver transplantation. Three months posttransplant thrombomodulin resistance persisted. Whereas this contributes to thrombotic complications observed after liver transplantation, remains to be elucidated. |
| format | Article |
| id | doaj-art-c58b149ecded4ffca1fd0aeb63cb9ef7 |
| institution | DOAJ |
| issn | 2475-0379 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj-art-c58b149ecded4ffca1fd0aeb63cb9ef72025-08-20T03:18:58ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792025-02-019210270910.1016/j.rpth.2025.102709Persisting thrombomodulin resistance at 3 months after liver transplantation in children with cirrhosisMarie-Astrid van Dievoet0Clara David1Audrey Dieu2Cedric Hermans3Thierry Pirotte4Jonathan Douxfils5Ton Lisman6Xavier Stephenne7Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Brussels, Belgium; Laboratory Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Correspondence Marie-Astrid van Dievoet, Laboratory Department, Cliniques universitaires Saint-Luc, 54 Avenue Hippocrate, B-1200 Brussels, Belgium.Clinical Pharmacology and Toxicology Research Unit, Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium; Research and Development Department, QUALIblood s.a., QUALIresearch, Liège, BelgiumDepartment of Anesthesiology, Cliniques Universitaires Saint-Luc, 1200 Brussels, BelgiumHaemostasis and Thrombosis Unit, Division of Haematology, Cliniques Universitaires Saint-Luc, Brussels, BelgiumDepartment of Anesthesiology, Cliniques Universitaires Saint-Luc, 1200 Brussels, BelgiumClinical Pharmacology and Toxicology Research Unit, Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium; Research and Development Department, QUALIblood s.a., QUALIresearch, Liège, BelgiumSurgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsLaboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Brussels, Belgium; Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Cliniques Universitaires Saint-Luc, Rare Liver ERN, Transplantchild ERN, Brussels, BelgiumBackground: The coagulation cascade in pediatric cirrhotic patients appears rebalanced, similar to adults, with few true hemostasis-related bleeds or thromboembolic events before liver transplantation. Vascular thrombosis is an important post–liver transplantation complication. Few papers have addressed the recovery of the coagulation cascade after liver transplantation. Objectives: We aimed to assess the coagulation cascade, with both measurement of individual factors and a global hemostasis assay, before living donor liver transplantation and to investigate its recovery 3 months after transplantation, when liver function has normalized. Methods: From January 2022 to July 2023, pediatric cirrhotic patients were prospectively enrolled 1 day before liver transplantation. An age-matched control group was included for comparison. Routine hemostasis tests, levels of coagulation factors and natural anticoagulants, and thrombomodulin-modified thrombin generation were determined on automated coagulation analyzers at inclusion and 3 months after liver transplantation. Results: Twenty-seven pediatric patients with cirrhosis, primarily of cholestatic origin, and 10 controls were enrolled. Sixteen patients were sampled 3 months after liver transplantation. Pediatric end-stage liver disease scores ranged from −10 to 44. A rebalanced coagulation cascade was confirmed in cirrhotic children, indicated by a thrombomodulin-modified thrombin generation assay similar to controls, although with higher interpatient variability. Interestingly, 3 months posttransplant, coagulation was not completely normalized. In the majority of patients resistance to thrombomodulin persisted. Conclusion: This study confirmed a rebalanced coagulation system in pediatric cirrhotic patients before liver transplantation. Three months posttransplant thrombomodulin resistance persisted. Whereas this contributes to thrombotic complications observed after liver transplantation, remains to be elucidated.http://www.sciencedirect.com/science/article/pii/S2475037925000330liver cirrhosisliver transplantationpediatricsthrombomodulinthrombin generation |
| spellingShingle | Marie-Astrid van Dievoet Clara David Audrey Dieu Cedric Hermans Thierry Pirotte Jonathan Douxfils Ton Lisman Xavier Stephenne Persisting thrombomodulin resistance at 3 months after liver transplantation in children with cirrhosis Research and Practice in Thrombosis and Haemostasis liver cirrhosis liver transplantation pediatrics thrombomodulin thrombin generation |
| title | Persisting thrombomodulin resistance at 3 months after liver transplantation in children with cirrhosis |
| title_full | Persisting thrombomodulin resistance at 3 months after liver transplantation in children with cirrhosis |
| title_fullStr | Persisting thrombomodulin resistance at 3 months after liver transplantation in children with cirrhosis |
| title_full_unstemmed | Persisting thrombomodulin resistance at 3 months after liver transplantation in children with cirrhosis |
| title_short | Persisting thrombomodulin resistance at 3 months after liver transplantation in children with cirrhosis |
| title_sort | persisting thrombomodulin resistance at 3 months after liver transplantation in children with cirrhosis |
| topic | liver cirrhosis liver transplantation pediatrics thrombomodulin thrombin generation |
| url | http://www.sciencedirect.com/science/article/pii/S2475037925000330 |
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