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Published on: February 27, 2026
Thrombin Generation in Acute and Chronic Liver Disease in Children
Giovina Di Felice1, Anna Lisa Montemari1, Andrea Pietrobattista2
1Clinical Laboratory Unit, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.
Insights
Prothrombin time (PT-INR) does not fully assess coagulation in pediatric liver disease. Thrombin generation assay (TGA) offers a more complete picture of hemostasis, providing valuable complementary information beyond standard tests.
Area of Science:
- Pediatric Hematology
- Hepatology
- Coagulation Science
Background:
- Pediatric liver disease often presents with abnormal coagulation tests.
- Prothrombin time (PT-INR) offers an incomplete assessment of global hemostatic balance.
- Thrombin generation assay (TGA) may provide complementary insights in acute liver failure (ALF) and chronic liver disease (CLD).
Purpose of the Study:
- To compare thrombin generation assay (TGA) with conventional coagulation tests in pediatric liver disease.
- To assess the utility of TGA in reflecting global hemostatic balance in children with ALF and CLD.
- To explore correlations between PT-INR and TGA parameters.
Main Methods:
- Enrolled 61 pediatric patients with liver disease and 51 healthy controls.
- Measured thrombin generation using ST Genesia (STG) with normalization to reference plasma.
- Utilized non-parametric tests, correlation analysis, and principal component analysis (PCA).
Main Results:
- PT-INR was significantly elevated in patients, especially with ALF.
- Patients exhibited reduced fibrinogen, procoagulant/anticoagulant factors, and increased factor VIII.
- Correlations between PT-INR and TGA parameters were weak; PCA indicated TGA provides complementary information.
Conclusions:
- Conventional PT-INR does not reliably reflect global coagulation in pediatric liver disease.
- Thrombin generation testing offers integrative hemostatic information.
- TGA may enhance laboratory assessment beyond conventional coagulation tests.
Abstract:
Background: Pediatric liver disease is frequently associated with abnormal conventional coagulation tests; however, prothrombin time expressed as international normalized ratio (PT-INR) incompletely reflect global hemostatic balance. Thrombin generation assay (TGA) provide an integrated assessment of coagulation and may offer complementary information in children with acute liver failure (ALF) and chronic liver disease (CLD). Methods: We enrolled 61 pediatric patients with liver disease (50 CLD, 8 ALF, 3 extrahepatic portal vein obstruction EHPVO) and 51 healthy controls. Platelet-poor plasma was prepared according to international recommendations. Thrombin generation was measured using ST Genesia (STG) with normalization to reference plasma. Group comparisons were performed using non-parametric tests; correlations between PT-INR and thrombin generation parameters were assessed, and principal component analysis (PCA) was used to explore the variance structure of thrombin generation indices and conventional coagulation variables. Results: PT-INR was significantly higher in patients than controls, particularly in ALF. Bleeding events were uncommon. Compared with controls, patients showed reduced levels of fibrinogen and multiple procoagulant/anticoagulant factors (including antithrombin and protein C), with increased factor VIII. Among thrombin generation parameters, the endogenous thrombin potential (ETP) ratio differed significantly across groups (p = 0.001), while correlations between PT-INR and thrombin generation parameters were weak or absent, no significant associations were observed even at higher Pediatric/Model for End-Stage Liver Disease scores. PCA separated thrombin generation indices from PT-INR and conventional coagulation factors, suggesting complementary information. Conclusions: In pediatric liver disease, PT-INR does not reliably reflect global coagulation capacity. Thrombin generation testing provides additional, integrative information on hemostasis and may improve laboratory assessment beyond conventional tests.
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