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Evidence for a rebalanced hemostatic system in pediatric liver transplantation: A prospective cohort study
Maureen J M Werner1,2, Vincent E de Meijer1, Jelle Adelmeijer2
1Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Insights
Pediatric liver transplant recipients exhibit a temporary hypocoagulable state during surgery, followed by a persistent hypercoagulable state post-transplant, increasing thrombosis risk.
Area of Science:
- Pediatric Hematology
- Transplantation Medicine
- Hemostasis and Thrombosis
Background:
- Children with end-stage liver disease have developing hemostatic systems and higher thrombosis risks compared to adults.
- Liver transplantation in children involves complex hemostatic challenges due to disease and surgical factors.
Purpose of the Study:
- To evaluate the hemostatic status in children undergoing liver transplantation, both during and after the procedure.
- To characterize changes in coagulation pathways and identify potential thrombosis risks in pediatric liver transplant patients.
Main Methods:
- Serial blood sampling from 20 pediatric liver transplant recipients (≤16 years) and 30 age-matched controls.
- Analysis included routine coagulation tests, thrombomodulin-modified thrombin generation, clot lysis times, and hemostatic protein levels.
- Assessment of hemostasis during and up to 30 days post-transplantation.
Main Results:
- Patients presented with thrombocytopenia and elevated Von Willebrand factor and ADAMTS13 levels.
- Prolonged prothrombin time and activated partial thromboplastin time were observed during transplantation, except when heparin was administered.
- Elevated fibrinogen, factor VIII, and increased clot lysis times persisted for at least 30 days post-transplant, indicating a hypercoagulable state.
Conclusions:
- Children with end-stage liver disease maintain a delicate hemostatic balance.
- Liver transplantation induces a transient hypocoagulable state followed by a sustained hypercoagulable state.
- This post-transplant hypercoagulability may be a significant factor in the increased risk of thrombosis in pediatric recipients.
Abstract:
In adults with end-stage liver disease concurrent changes in pro- and antihemostatic pathways result in a rebalanced hemostasis. Children though, have a developing hemostatic system, different disease etiologies, and increased risk of thrombosis. This study aimed to assess the hemostatic state of children during and after liver transplantation. Serial blood samples were obtained from 20 children (≤16 years) undergoing primary liver transplantation (September 2017-October 2018). Routine hemostasis tests, thrombomodulin-modified thrombin generation, clot lysis times, and hemostatic proteins were measured. Reference values were established using an age-matched control group of 30 children. Thrombocytopenia was present in study patients. Von Willebrand factors were doubled and ADAMTS13 levels decreased during and after transplantation up until day 30, when platelet count had normalized. Whereas prothrombin time and activated partial thromboplastin time were prolonged during transplantation, thrombin generation was within normal ranges, except during perioperative heparin administration. Fibrinogen, factor VIII levels, and clot lysis time were elevated up until day 30. In conclusion, children with end-stage liver disease are in tight hemostatic balance. During transplantation a temporary heparin-dependent hypocoagulable state is present, which rapidly converts to a hemostatic balance with distinct hypercoagulable features that persist until at least day 30. This hypercoagulable state may contribute to the risk of posttransplant thrombosis.
