Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Thromb Haemost. 2020 Sep;120(9):1240-1247. doi: 10.1055/s-0040-1713752. Epub 2020 Jul 6.
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.
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.
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.
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.
在小儿肝移植中，常使用促凝和抗凝药物来预防和治疗血栓和出血并发症。然而，儿童肝病的基础止血变化与移植引起的其他变化相结合，使得这一问题极具挑战性。本研究旨在分析在接受肝移植的儿童的血浆中，临床可用的促凝和抗凝药物的疗效。
在 20 名患有终末期肝病并接受肝移植的儿童（≤16 岁）的血浆样本中，测试了促凝和抗凝药物对凝血酶生成能力的体外影响，并与 30 名年龄匹配的健康对照进行了比较。
添加混合正常血浆对患者和对照者均无影响，而 4 因子凝血酶原复合物浓缩物增加了患者和对照者的凝血酶生成，患者的活性增强。在移植开始时，达比加群酯和未分级肝素在患者中的抗凝作用更强，而在移植后 30 天，低分子肝素在患者中的作用稍弱。利伐沙班在患者和对照者中的作用相当。
本研究揭示了在接受肝移植的终末期肝病儿童中，常用的促凝和抗凝药物的疗效存在重要差异。因此，可能需要调整这些药物的剂量。本研究的结果可能有助于制定急需的方案，以预防和治疗小儿肝移植中的出血和血栓并发症。
