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

Thromb Haemost. 2020 Sep;120(9):1240-1247. doi: 10.1055/s-0040-1713752. Epub 2020 Jul 6.

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.

MeSH terms

  • Anticoagulants / pharmacology*
  • Anticoagulants / therapeutic use
  • Blood Coagulation / drug effects*
  • Blood Coagulation Factors / pharmacology
  • Blood Coagulation Factors / therapeutic use
  • Child
  • Child, Preschool
  • Dabigatran / pharmacology
  • Dabigatran / therapeutic use
  • End Stage Liver Disease / blood
  • End Stage Liver Disease / therapy*
  • Female
  • Hemostatics / pharmacology*
  • Hemostatics / therapeutic use
  • Heparin / pharmacology
  • Heparin / therapeutic use
  • Humans
  • Liver Transplantation*
  • Male
  • Rivaroxaban / pharmacology
  • Rivaroxaban / therapeutic use

Substances

  • Anticoagulants
  • Blood Coagulation Factors
  • Hemostatics
  • prothrombin complex concentrates
  • Heparin
  • Rivaroxaban
  • Dabigatran