Key result
dTT and ECA demonstrate ~91% agreement for dabigatran quantification but overestimate levels compared to UPLC-MS.
Why the study?
Limited observational data existed comparing dabigatran quantification methods, which are needed for decision-making regarding urgent surgery or reversal.
Do diluted thrombin time and ecarin chromogenic assays accurately quantify dabigatran plasma levels compared to UPLC-MS in healthy volunteers?
Do diluted thrombin time and ecarin chromogenic assays accurately quantify dabigatran plasma levels compared to UPLC-MS in healthy volunteers?
Effect estimate: Agreement probability 90.6% (Cohen's kappa 0.84) (95% CI 88.4-92.5)
Diluted thrombin time and ecarin chromogenic assays provide rapid and accurate dabigatran level quantification suitable for emergency clinical practice, with slight overestimation due to active metabolites.
Supports cautious use for emergency dabigatran monitoring with noted overestimation; extends assay validation but leaves open performance in treated patients.
INTRODUCTION: The knowledge of dabigatran levels is helpful for decision-making in specific situations such as urgent surgery or when the question of reversal arises (uncontrolled bleeding, eligibility for thrombolysis). However, a limited number of observational studies are available regarding comparisons between quantification methods. The objective of the study was to compare dabigatran plasma levels using three assays including the reference method (high-performance liquid chromatography coupled with mass spectrometry), focusing on the agreement around the 30-50 ng/mL clinically relevant thresholds. METHODS: Sixty healthy volunteers from DRIVING trial (NCT01627665) were given a single 300-mg dabigatran etexilate dose. Serial blood samplings were performed at pre-defined time points (0 to 24 h). We analyzed plasma samples using ultra-performance-liquid chromatography coupled with tandem mass spectrometry (UPLC-MS) (dabigatran reference method); ii/diluted thrombin time (dTT) (Hemoclot-DTI-Hyphen-Biomed); iii/ecarin-based chromogenic assay (ECA-II-Stago). RESULTS: Nine hundred sixty samples were analyzed using the three assays (2759 values). dTT and ECA-II values were highly correlated with those of UPLC-MS (Deming regression). Most values >50 ng/mL were higher using dTT and ECA-II compared to UPLC-MS: biases were constant, +14% and +16% with dTT and ECA-II, respectively (Bland-Altman plots), suggesting that active metabolites accounted for ~15% of thrombin inhibition. Regarding values <30 ng/mL, 30-50 ng/mL, or ≥50 ng/mL, the agreement probability between dTT and ECA-II was of 90.6% [88.4-92.5] (Cohen's kappa coefficient 0.84). CONCLUSION: dTT and ECA-II assays rapidly provide accurate dabigatran-level results for clinical practice, both assays being suitable in emergency, taking into account the thrombin inhibitory effect of dabigatran metabolites.
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Fautereau-Vassel et al. (2023) studied healthy volunteers (n=60). Diluted thrombin time (dTT) and ecarin-based chromogenic assay (ECA-II) vs. UPLC-MS (reference method) was evaluated on Agreement probability between dTT and ECA-II for clinically relevant thresholds (<30 ng/mL, 30-50 ng/mL, or ≥50 ng/mL) (Agreement probability 90.6% (Cohen's kappa 0.84), 95% CI 88.4-92.5). Diluted thrombin time and ecarin-based chromogenic assays showed high agreement (90.6%; 95% CI 88.4-92.5) for dabigatran quantification, with constant biases of +14% and +16% compared to UPLC-MS.
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