Estimation of dabigatran plasma concentrations in the perioperative setting

Jonathan Douxfils; Sarah Lessire; Anne-Sophie Dincq; Paul Hjemdahl; Yuko Rönquist-Nii; Anton Pohanka; Maximilien Gourdin; Bernard Chatelain; Jean-Michel Dogné; François Mullier

doi:10.1160/TH14-09-0808

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2015; 113(04): 862-869
DOI: 10.1160/TH14-09-0808

New Technologies, Diagnostic Tools and Drugs

Schattauer GmbH

Estimation of dabigatran plasma concentrations in the perioperative setting

An ex vivo study using dedicated coagulation assays

Jonathan Douxfils^*

¹Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Belgium

,

Sarah Lessire^*

¹Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Belgium

²Department of Anaesthesiology, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), CHU Dinant Godinne UcL Namur, Université Catholique de Louvain, Belgium

,

Anne-Sophie Dincq

²Department of Anaesthesiology, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), CHU Dinant Godinne UcL Namur, Université Catholique de Louvain, Belgium

,

Paul Hjemdahl

³Department of Clinical Pharmacology, Karolinska University Hospital and Clinical Pharmacology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden

,

Yuko Rönquist-Nii

³Department of Clinical Pharmacology, Karolinska University Hospital and Clinical Pharmacology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden

,

Anton Pohanka

³Department of Clinical Pharmacology, Karolinska University Hospital and Clinical Pharmacology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden

,

Maximilien Gourdin

²Department of Anaesthesiology, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), CHU Dinant Godinne UcL Namur, Université Catholique de Louvain, Belgium

,

Bernard Chatelain

⁴Haematology Laboratory, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), CHU Dinant Godinne UcL Namur, Université Catholique de Louvain, Belgium

,

Jean-Michel Dogné

¹Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Belgium

,

François Mullier

¹Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Belgium

⁴Haematology Laboratory, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), CHU Dinant Godinne UcL Namur, Université Catholique de Louvain, Belgium

› Institutsangaben

Abstract

Summary

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.

Keywords

Dabigatran - monitoring - perioperative - guidelines

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Referenzen

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