van Dievoet Marie-Astrid, David Clara, Dieu Audrey, Hermans Cedric, Pirotte Thierry, Douxfils Jonathan, Lisman Ton, Stephenne Xavier
Laboratory 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.
Res Pract Thromb Haemost. 2025 Feb 27;9(2):102709. doi: 10.1016/j.rpth.2025.102709. eCollection 2025 Feb.
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.
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.
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.
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.
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.
小儿肝硬化患者的凝血级联反应似乎与成人相似，处于重新平衡状态，在肝移植前很少发生真正与止血相关的出血或血栓栓塞事件。血管血栓形成是肝移植后的一种重要并发症。很少有论文探讨肝移植后凝血级联反应的恢复情况。
我们旨在在活体肝移植前通过测量个体凝血因子和进行整体止血检测来评估凝血级联反应，并研究在移植后3个月肝功能恢复正常时其恢复情况。
从2022年1月至2023年7月，小儿肝硬化患者在肝移植前1天被前瞻性纳入研究。纳入一个年龄匹配的对照组进行比较。在纳入研究时和肝移植后3个月，使用自动凝血分析仪测定常规止血试验、凝血因子和天然抗凝剂水平以及血栓调节蛋白修饰的凝血酶生成情况。
纳入了27例主要为胆汁淤积性起源的小儿肝硬化患者和10例对照组。16例患者在肝移植后3个月进行了采样。小儿终末期肝病评分范围为-10至44。尽管患者间变异性较高，但通过与对照组相似的血栓调节蛋白修饰的凝血酶生成试验证实了肝硬化患儿的凝血级联反应重新平衡。有趣的是，移植后3个月，凝血并未完全恢复正常。在大多数患者中，对血栓调节蛋白的抵抗持续存在。
本研究证实了小儿肝硬化患者在肝移植前凝血系统重新平衡。移植后3个月，对血栓调节蛋白的抵抗仍然存在。虽然这导致了肝移植后观察到的血栓并发症，但其原因仍有待阐明。
