Measuring Dabigatran Concentrations Using a Chromogenic Ecarin Clotting Time Assay

Abstract

Background: Clinicians managing patients receiving the direct thrombin inhibitor dabigatran may benefit in being able to determine the amount of drug present in selected situations. This may include assessment of accumulation, concurrent drug interactions, or adequate removal from circulation. The ability to estimate the amount of dabigatran present using the chromogenic ecarin assay (ECA) requires further clarification. Objective: To describe the reliability of dabigatran measurements using a chromogenic ECA. Methods: This was an evaluation of the ECA method that incorporated assessment of imprecision, linearity, accuracy, carryover, and lower limits of detection or blank. Pooled normal plasma enriched with dabigatran at concentrations of 0, 25, 50, 75, 100, 125, 150, 200, 300, 400, and 500 ng/mL were sent blinded to 3 laboratories in the United States to compare our ECA results with those of laboratories reporting dilute thrombin time methods (HEMOCLOT thrombin inhibitor assay) for measuring dabigatran. Trough and peak levels from 35 patients were also compared with mass spectrophotometry for assessing ECA accuracy. Results: The within-run or day-to-day imprecision was less than 10%, with high linearity (R² = 0.989) and high degree of accuracy (R² = 0.985; slope = 0.908) for levels ranging between 18 and 470 ng/mL and no carryover at 0 ng/mL noted. The ECA approach appeared to be more reliable at lower dabigatran concentrations. Conclusions: The chromogenic ECA appears to be an effective approach to determine the amount of dabigatran present. Further insights are necessary to determine how it can be used to reduce thromboembolic or bleeding complications in patients receiving dabigatran