Monitoring of low dabigatran concentrations: diagnostic performance at clinically relevant decision thresholds

The direct oral anticoagulant dabigatran does not require therapeutic drug monitoring, however emergency measurements are gaining importance. Current assays feature good performance at intermediate and high dabigatran concentrations but show limited accuracy at low concentrations. This area requires more attention as clinical decision threshold values currently lie at 30 and 50 ng/ml. The objective of the study was to evaluate and compare diagnostic performance of dabigatran assays at these thresholds. Dabigatran concentrations of 293 plasma samples taken from 50 patients were measured with the INNOVANCE direct thrombin inhibitor assay (DTI) from Siemens, the Biophen direct thrombin inhibitor assay (BDTI), the BDTI using a low range calibrator (BDTI-low), the Hemoclot direct thrombin inhibitor assay (HTI) and an ecarin clotting time assay (ECT). Assay results were compared to ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and test characteristics were calculated for thresholds of 30 and 50 ng/ml. DTI, BDTI-low and ECT showed very strong correlation and high agreement with UPLC-MS/MS and an improved determination of low dabigatran concentrations. ROC curve analyses revealed very high accuracy at the 30/50 ng/ml thresholds for DTI (AUC = 0.989/0.995), BDTI-low (AUC = 0.980/0.991) and ECT (AUC = 0.990/0.996) measurements. Sensitivity and specificity in detecting were calculated for DTI (98/92%), BDTI-low (87/95%), ECT (97/96%), BDTI (99/82%) and HTI (86/89%) measurements. Compared to the previously available HTI and BDTI, both novel assays, DTI and BDTI-low, reliably determine low dabigatran plasma concentrations around the clinical decision thresholds with very high sensitivity and specificity.