Assessment of Thrombin Generation in Pediatric Patients on Extracorporeal Life Support: Impact of Bivalirudin and Other Anticoagulants
Vadim Kostousov, Karen Bruzdoski, Amir Navaei, Jun TeruyaABSTRACT
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.