How to best monitor bivalirudin anticoagulant effect for ECMO and VAD-Comparison of four assay methods

Introduction Unfractionated heparin is widely used as an anticoagulant for extracorporeal life support (ECLS) and usually monitored with activated partial thromboplastin time (aPTT). Due to its limitations in pediatric populations and interferences with monitoring, bivalirudin is being utilized more frequently in these settings. For bivalirudin, other tests have emerged such as dilute thrombin time (dTT) and ecarin chromogenic assay (ECA); however, their utilities in pediatrics are unexplored. Development of suitable, accurate testing for bivalirudin monitoring is paramount to prevent complications. We sought to compare aPTT, aPTT with heparinase (HPTT), dTT1:4, modified dTT1:10, and ECA for monitoring of pediatric ECLS patients anticoagulated with bivalirudin. Methods aPTT, HPTT, dTT1:4, dTT1:10, and ECA were measured in 51 specimens from 17 children on bivalirudin-anticoagulated ECLS. Normal pooled plasma was spiked with various bivalirudin concentrations, and aPTT, dTT1:4, dTT1:10, and ECA were measured. In addition, dTT assays were performed using plasma from normal donors spiked with bivalirudin, heparin, and cryoprecipitate. Results dTT1:4 showed excellent correlation with ECA, while dTT1:4 correlated moderately with aPTT or HPTT. Fifty to 75% of specimens showed discordant results between dTT1:4 and HPTT. We found that dTT1:4 and ECA prolongations are associated with bivalirudin infusion rate; however, there are age-based differences that should be accounted for. The performance of dTT1:10 was similar to dTT1:4, though it was less sensitive to interfering factors (heparin or hyperfibrinogenemia). Conclusion dTT1:10 appears to be more suitable for routine practice due to fewer variations and lower cost for monitoring bivalirudin in pediatric ECLS.