BACKGROUND: Dabigatran is an oral direct thrombin inhibitor for which routine 
laboratory monitoring is currently not recommended. However, there are 
situations in which measurements of the drug and its effect are desirable. We 
therefore compared and validated different coagulation methods for assessments 
of dabigatran in clinical samples in relation to measurements of plasma 
dabigatran, without the purpose of establishing effective and safe 
concentrations of dabigatran in plasma.
METHODS: Samples were obtained from 70 atrial fibrillation patients treated with 
dabigatran etexilate. Plasma concentrations were measured using liquid 
chromatography-tandem mass spectrometry (LC-MS/MS) and were compared with 
coagulation methods Hemoclot thrombin inhibitors (HTI) and Ecarin clotting assay 
(ECA), as well as with prothrombin time-international normalized ratio (PT-INR) 
and activated partial thromboplastin time (aPTT).
RESULTS: A wide range of dabigatran concentrations was determined by LC-MS/MS 
(<0.5-586 ng/mL). Correlations between LC-MS/MS results and estimated 
concentrations were excellent for both HTI and ECA overall (r(2) = 0.97 and 0.96 
respectively, p < 0.0001), but the precision and variability of these assays 
were not fully satisfactory in the low range of dabigatran plasma 
concentrations, in which ECA performed better than HTI. aPTT performed poorly, 
and was normal (<40 s) even with dabigatran levels of 60 ng/mL. PT-INR was 
normal even at supratherapeutic dabigatran concentrations.
CONCLUSION: LC-MS/MS is the gold standard for measurements of dabigatran in 
plasma. Alternatively, either HTI or ECA assays may be used, but neither of 
these assays is dependable when monitoring low levels or to infer total absence 
of dabigatran. The aPTT assay is relatively insensitive to dabigatran, and 
normal aPTT results may be observed even with therapeutic dabigatran 
concentrations.