Coagulation Monitoring Correlation with Bivalirudin Dosing in Pediatric Ventricular Assist Device Support

Abstract

The use of bivalirudin has increased dramatically for primary thromboprophylaxis in pediatric paracorporeal ventricular assist device (VAD) support with limited data on optimal monitoring of effect. Partial thromboplastin time (aPTT) is commonly used for monitoring of bivalirudin, but can be impacted by line heparin, variability in assays and other patient factors. As such, we sought to examine the correlation of PTT to International Normalized Ratio (INR), as a possible monitoring tool for bivalirudin in in pediatric VAD patients. Retrospective single center study of all children aged <19 years, treated with bivalirudin for anticoagulation of paracorporeal VAD support. Pearson correlation coefficient was calculated for aPTT -INR and heparin absorbed (HA) aPTT-INR paired samples for each patient over the course of their support with each sample drawn at the same time. From 2015-2019, eleven patients (4 female), median age 5 months (range 0.5-40 months), weighing 7.8 kg (3.4-17.0kg) and body surface area of 0.4 m2 (range 0.2-0.7 m2) at time of implant were treated with bivalirudin for paracorporeal VAD thromboprophylaxis, of which 6 were on EXCOR devices, 4 were transitioned between continuous flow and EXCOR devices, and 1 patients was on CardioHelp extracorporeal membrane oxygenator connected to EXCOR cannula. A total of 900 days of paracorporeal VAD support generated 3,143 laboratory values for correlation. Correlations varied between aPTT assays, with highest median correlation coefficient for HA aPTT to INR of 0.72 (min 0.57 to max 0.81) in 4 patients with a total of 662 paired samples, as compared to correlation coefficient for aPTT to INR of 0.56 (min 0.32-0.91) in 10 patients with a total of 1,188 paired samples. Correlations varied between patients, with no association to age, device type or survival outcomes. The most important determinant for lack of correlation between aPTT to INR was concomitant administration of line heparin. Patients treated with bivalirudin demonstrate individual correlations of their INR to PTT, with highest correlation to HA PTT by accounting for exogenous line heparin. This preliminary data provides foundation for ongoing study into the utility of INR for bivalirudin dosing and possible future application of point of care INR testing in this population.