Comprehensive characteristics of the anticoagulant activity of dabigatran in relation to its plasma concentration

Willemijn J Comuth, Linda Ø Henriksen, Daan van de Kerkhof, Steen E Husted, Steen D Kristensen, Moniek P M de Maat, Anna-Marie B Münster

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Abstract

BACKGROUND: Issues with laboratory measurement of dabigatran include: 1. Do coagulation assays reflect dabigatran plasma concentrations? 2. Do samples from patients treated with dabigatran have the same coagulability as dabigatran-spiked samples from healthy volunteers? 3. What is the long-term stability of dabigatran after storage at -80 °C? This study aims to evaluate these questions.

MATERIALS AND METHODS: Ecarin chromogenic assay (ECA), a laboratory-developed diluted thrombin time (LD-dTT), prothrombin time (PT) and activated partial thromboplastin time (APTT) and ROTEM® were used to measure dabigatran anticoagulant activity and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure dabigatran plasma concentrations. ROTEM® (EXTEM, INTEM, FIBTEM) was performed in whole blood and the other assays in platelet poor plasma (PPP), both in samples spiked with dabigatran (0, 25, 50, 100, 250, 500 and 1000 ng/mL) from healthy donors and in ex vivo samples from patients treated with dabigatran etexilate. Citrated PPP samples were frozen and stored at -80 °C, 1, 3, 6 and 12 months until analysis.

RESULTS: EXTEM and FIBTEM clotting time (CT), ECA and LD-dTT correlate well with dabigatran plasma concentrations. With the exception of few ROTEM® parameters, there were no differences between spiked and patient samples. Samples were stable for at least 12 months at -80 °C.

CONCLUSIONS: EXTEM and FIBTEM CT, ECA and LD-dTT are suitable for measuring the effect of dabigatran in treated patients. In general, results from spiked plasma samples are similar to those of patient samples. Storage of dabigatran plasma samples for up to 12 months does not influence measured levels.

Original languageEnglish
JournalThrombosis Research
Volume164
Pages (from-to)32-39
ISSN0049-3848
DOIs
Publication statusPublished - 2018

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