Assessment of Thrombin Generation in Pediatric Patients on Extracorporeal Life Support: Impact of Bivalirudin and Other Anticoagulants
4 affiliations
- 1Department of Pathology & Immunology Baylor College of Medicine Houston Texas USA
- 2Department of Pathology, Division of Transfusion Medicine & Coagulation Texas Children's Hospital Houston Texas USA
- 3Department of Pediatrics, Division of Critical Care Medicine & Cardiology Baylor College of Medicine Houston Texas USA
- 4Department of Medicine Baylor College of Medicine Houston Texas USA
Abstract
Introduction: Bivalirudin is an alternative anticoagulant to heparin and is widely used in pediatric extracorporeal life support (ECLS). Its activity is monitored using activated partial thromboplastin time (aPTT) and/or more specific tests such as plasma‐diluted thrombin time (dTT). A new automated thrombin generation assay (TGA) has also shown promise in evaluating the hemostatic response in anticoagulated patients; however, its utility for monitoring bivalirudin or other anticoagulants in pediatrics remains unknown. We aimed to evaluate TGA in pediatric patients treated with bivalirudin and to compare it with that observed in patients receiving other commonly used anticoagulants.
Methods: TGA, aPTT, aPTT with hepzyme, dTT, INR were measured in 30 specimens from 12 pediatric ECLS patients anticoagulated with bivalirudin. In addition, TGA, anti‐Xa assay, and INR were measured in samples from children receiving enoxaparin (n = 22, 10 patients), heparin (n = 16, 8 patients), and warfarin (n = 19, 6 patients).
Results: TGA lag ratio showed a strong correlation with bivalirudin concentration as measured by dTT and ROC analysis demonstrated that a Lag ratio > 2.0 predicted specimens within the therapeutic range for bivalirudin (sensitivity 0.88, specificity 0.67, accuracy 0.79). Interestingly, samples containing endogenous heparin‐like substances exhibited paradoxically enhanced thrombin generation, despite having the highest aPTT values. Enoxaparin effect was associated with a reduction in thrombin peak and endogenous thrombin potential (ETP) suppression, while both heparin and warfarin led to a prolonged lag time, along with decreased peak and greater ETP suppression.
Conclusion: TGA shows promise in evaluating bivalirudin anticoagulation and is capable of detecting anticoagulant activity across both subtherapeutic and therapeutic levels of other agents commonly used in pediatric patients.
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BibTeX
@article{kostousov2026assessment,
title = {{Assessment of Thrombin Generation in Pediatric Patients on Extracorporeal Life Support: Impact of Bivalirudin and Other Anticoagulants}},
author = {Vadim Kostousov and Karen Bruzdoski and Amir Navaei and Jun Teruya},
journal = {International Journal of Laboratory Hematology},
year = {2026},
month = aug,
doi = {10.1111/ijlh.70223},
url = {https://doi.org/10.1111/ijlh.70223},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Assessment of Thrombin Generation in Pediatric Patients on Extracorporeal Life Support: Impact of Bivalirudin and Other Anticoagulants
AU - Vadim Kostousov
AU - Karen Bruzdoski
AU - Amir Navaei
AU - Jun Teruya
PY - 2026
DA - 2026/08/16
JO - International Journal of Laboratory Hematology
DO - 10.1111/ijlh.70223
UR - https://doi.org/10.1111/ijlh.70223
AB - Introduction: Bivalirudin is an alternative anticoagulant to heparin and is widely used in pediatric extracorporeal life support (ECLS). Its activity is monitored using activated partial thromboplastin time (aPTT) and/or more specific tests such as plasma‐diluted thrombin time (dTT). A new automated thrombin generation assay (TGA) has also shown promise in evaluating the hemostatic response in anticoagulated patients; however, its utility for monitoring bivalirudin or other anticoagulants in pediatrics remains unknown. We aimed to evaluate TGA in pediatric patients treated with bivalirudin and to compare it with that observed in patients receiving other commonly used anticoagulants. Methods: TGA, aPTT, aPTT with hepzyme, dTT, INR were measured in 30 specimens from 12 pediatric ECLS patients anticoagulated with bivalirudin. In addition, TGA, anti‐Xa assay, and INR were measured in samples from children receiving enoxaparin (n = 22, 10 patients), heparin (n = 16, 8 patients), and warfarin (n = 19, 6 patients). Results: TGA lag ratio showed a strong correlation with bivalirudin concentration as measured by dTT and ROC analysis demonstrated that a Lag ratio > 2.0 predicted specimens within the therapeutic range for bivalirudin (sensitivity 0.88, specificity 0.67, accuracy 0.79). Interestingly, samples containing endogenous heparin‐like substances exhibited paradoxically enhanced thrombin generation, despite having the highest aPTT values. Enoxaparin effect was associated with a reduction in thrombin peak and endogenous thrombin potential (ETP) suppression, while both heparin and warfarin led to a prolonged lag time, along with decreased peak and greater ETP suppression. Conclusion: TGA shows promise in evaluating bivalirudin anticoagulation and is capable of detecting anticoagulant activity across both subtherapeutic and therapeutic levels of other agents commonly used in pediatric patients.
SN - 1751-5521
SN - 1751-553X
ER -