title: Estimation of dabigatran plasma concentrations in the perioperative setting. An ex vivo study using dedicated coagulation assays.
abstract: The perioperative management of dabigatran is challenging, and recommendations based on activated partial thromboplastin time (aPTT) and thrombin time (TT) are unsatisfactory. Dedicated coagulation tests have limitations at plasma concentrations < 50 ng/ml. Therefore, a more sensitive test, which is available 24/7, is required. It was the aim of this study to investigate the performance of the Hemoclot Thrombin Inhibitors® LOW (HTI LOW) kit, a diluted thrombin time, and the STA® - ECA II(ECA-II) kit, a chromogenic variant of the ecarin clotting time, that were developed to measure low dabigatran concentrations, compared to reference dabigatran analysis by liquid chromatography tandem mass-spectrometry (LC-MS/MS). This study included 33 plasma samples from patients treated with dabigatran etexilate who had plasma concentrations < 200 ng/ml. HTI LOW and ECA-II were performed along with HTI, aPTT (STA®-C. K.Prest® and SynthasIL®) and TT (STA® - Thrombin). All procedures were performed according to recommendations by the manufacturers. Linear (or curvilinear) correlations and Bland-Altman analyses were calculated. For free dabigatran concentrations < 50 ng/ml, the R² of linear correlations were 0.69, 0.84 and 0.61, with HTI, HTI LOW and ECA-II, respectively. The R² for TT, STA®-C. K.Prest® and SynthasIL® were 0.67, 0.42 and 0.15. For HTI, HTI LOW and ECA-II, Bland-Altman analyses revealed mean differences of -6 ng/ml (95 %CI: -25-14 ng/ml), 1 ng/ml (95 %CI: -18-19 ng/ml) and -1 ng/ml (95 %CI: -25-23 ng/ml), demonstrating that tests dedicated to measuring low concentrations are more accurate than HTI. In conclusion, the use of HTI LOW or ECA-II to assess low plasma dabigatran concentrations is supported by our findings.
authors.affiliation: Jonathan Douxfils, Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, B-5000, Belgium, E-mail: jonathan.douxfils@unamur.be.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Douxfils
authors.forename: Sarah
authors.initials: S
authors.lastname: Lessire
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Dincq
authors.forename: Paul
authors.initials: P
authors.lastname: Hjemdahl
authors.forename: Yuko
authors.initials: Y
authors.lastname: Rönquist-Nii
authors.forename: Anton
authors.initials: A
authors.lastname: Pohanka
authors.forename: Maximilien
authors.initials: M
authors.lastname: Gourdin
authors.forename: Bernard
authors.initials: B
authors.lastname: Chatelain
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dogné
authors.forename: François
authors.initials: F
authors.lastname: Mullier
mesh_terms: D000991:Antithrombins / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D001780:Blood Coagulation Tests; D016063:Blood Loss, Surgical / Q000517:prevention & control; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D000069604:Dabigatran / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D016014:Linear Models; D010314:Partial Thromboplastin Time; D019990:Perioperative Care; D019106:Postoperative Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012307:Risk Factors; D053719:Tandem Mass Spectrometry; D013918:Thrombin Time; D013997:Time Factors
chemical_list: D000991:Antithrombins; D000069604:Dabigatran
keywords: Dabigatran; guidelines; monitoring; perioperative