Abstract
Background Direct oral anticoagulants (DOACs) are increasingly replacing vitamin K antagonists
(VKA) for clinical indications requiring long-term oral anticoagulation. In contrast
to VKA, treatment with DOAC including dabigatran—the only direct thrombin inhibitor
amongst them—does not require therapeutic drug monitoring. However, in case of treatment
complications (e.g., major haemorrhage) and conditions requiring urgent surgery or
thrombolytic therapy, information about actual DOAC plasma levels is needed to guide
treatment decisions. Due to short reagent stability, limited accuracy at low dabigatran
levels and high heparin sensitivity, the applicability of the widely used Hemoclot
thrombin inhibitor (HTI) coagulation assay is limited in the emergency setting.
Methods Dabigatran concentrations of 288 citrated plasma samples taken from 48 dabigatran-treated
patients with drug concentrations of up to 300 ng/mL were measured with the chromogenic
anti-IIa Biophen direct thrombin inhibitor (BDTI) assay and results compared with
HTI using ultra performance liquid chromatography—tandem mass spectrometry as the
reference method for measuring dabigatran plasma concentrations.
Results BDTI results showed a very strong correlation with dabigatran concentrations (r = 0.965, p < 0.0001) as well as a low intra- and inter-assay variation of <5%. Compared with
HTI, BDTI provides an improved on-board reagent stability of 72 hours, rapid turnaround
times comparable to routine coagulation assays, high accuracy at low drug levels and
reduced heparin sensitivity.
Conclusion The BDTI is an ideal coagulation assay for the around-the-clock determination of
dabigatran plasma levels in clinical routine including emergency situations.
Keywords
oral anticoagulants - clinical trials - dabigatran - NOAC - DOAC
