title: The modification of the thrombin generation test for the clinical assessment of dabigatran etexilate efficiency.
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.
authors.affiliation: National Research Center for Hematology, Novyi Zykovskii pr., 4, Moscow, 125167, Russia.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Gribkova
authors.affiliation: Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Kosygina street, 4, Moscow, 119991, Russia.
authors.forename: Elena N
authors.initials: EN
authors.lastname: Lipets
authors.affiliation: National Research Center for Hematology, Novyi Zykovskii pr., 4, Moscow, 125167, Russia.
authors.forename: Irina G
authors.initials: IG
authors.lastname: Rekhtina
authors.affiliation: Central Institute of Traumatology and Orthopedics named after N.N. Priorov, Priorova Str., 10, Moscow, 127299, Russia.
authors.forename: Alex I
authors.initials: AI
authors.lastname: Bernakevich
authors.affiliation: Central Institute of Traumatology and Orthopedics named after N.N. Priorov, Priorova Str., 10, Moscow, 127299, Russia.
authors.forename: Dorzho B
authors.initials: DB
authors.lastname: Ayusheev
authors.affiliation: Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Ministry of Health, Samory Mashela Str., 1, Moscow, 117997, Russia.|Hematological Corporation "HemaCore" LLC, Naychnyi proezd 20, building 2, Moscow, 117246, Russia.
authors.forename: Ruzanna A
authors.initials: RA
authors.lastname: Ovsepyan
authors.affiliation: Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Kosygina street, 4, Moscow, 119991, Russia.|Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Ministry of Health, Samory Mashela Str., 1, Moscow, 117997, Russia.|Hematological Corporation "HemaCore" LLC, Naychnyi proezd 20, building 2, Moscow, 117246, Russia.|M.V. Lomonosov Moscow State University, 1 Lеninskie gory St., Moscow, 119991, Russia.
authors.forename: Fazoil I
authors.initials: FI
authors.lastname: Ataullakhanov
authors.affiliation: Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Kosygina street, 4, Moscow, 119991, Russia.|Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Ministry of Health, Samory Mashela Str., 1, Moscow, 117997, Russia.
authors.forename: Elena I
authors.initials: EI
authors.lastname: Sinauridze
mesh_terms: D000991:Antithrombins / Q000008:administration & dosage*; D001780:Blood Coagulation Tests / Q000379:methods*; D000069604:Dabigatran / Q000008:administration & dosage*; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D013927:Thrombosis / Q000517:prevention & control*
chemical_list: D000991:Antithrombins; D000069604:Dabigatran