Abstract
A new oral anticoagulant, dabigatran etexilate (DE, a prodrug of direct thrombin inhibitor (DTI) dabigatran), has been used clinically to prevent thrombosis. The assessment of dabigatran efficiency is necessary in some clinical cases, such as renal insufficiency, risk of bleeding, and drug interactions. However, a specific thrombin generation test (TGT) that is one of the most informative and sensitive to anticoagulant therapy (calibrated automated thrombinography (САТ)) shows a paradoxical increase of test parameters, such as endogenous thrombin potential (ETP) and peak thrombin, in patients receiving DE. The paradoxical behaviour of ETP and peak thrombin in these patients in the presence of DTIs is mostly caused by a decrease in the activity of thrombin in the α2-macroglobulin-thrombin complex that is used as a calibrator in CAT. For a correct estimation of the TGT parameters in patient’s plasma containing DTIs we proposed to use our previously described alternative calibration method that is based on the measurement of the fluorescence signal of a well-known concentration of the reaction product (7-amino-4-methylcoumarin). In this study, the validity of such approach was demonstrated in an ex vivo study in patients with knee replacement and two special patients with multiple myeloma, who received DE for thrombosis prophylaxis.
Highlights
Dabigatran), has been used clinically to prevent thrombosis
The possibility of inhibition of α2-macroglobulin-thrombin complex (α2MT) complex (ThrCal) in the presence of DTIs has been shown in ref. 32 and has been assumed in recent works, where the assessment of the efficiency of the clinical application of Dabigatran etexilate (DE) using
The authors even have concluded that the artificial increase in Endogenous thrombin potential (ETP) at low inhibitor concentrations disappears, if the first part of an area under thrombin generation curve is used for characterization of the thrombin generation, and this method may be well suited for a characterization of the thrombin generation in the plasma of patients
Summary
Dabigatran), has been used clinically to prevent thrombosis. The assessment of dabigatran efficiency is necessary in some clinical cases, such as renal insufficiency, risk of bleeding, and drug interactions. In parallel to CAT, parameters of TGT were determined from the same donor plasma samples in the presence of dabigatran or 19 s by the modified method with calibration of the fluorescence signal by AMC
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