CC BY-NC-ND 4.0 · Thromb Haemost
DOI: 10.1055/a-1549-6556
Original Article

Pharmacokinetics of direct oral anticoagulants in emergency situations – Results of the prospective observational RADOA-registry

Pharmacokinetics of direct oral anticoagulants in emergency situations
Edelgard Lindhoff-Last
1  CCB Coagulation Center and CCB Coagulation Research Center, Cardioangiology Center Bethanien Hospital (CCB), Frankfurt, Germany
,
Ingvild Birschmann
2  ILTM, HDZ NRW, Bad Oeynhausen, Germany
,
Joachim Kuhn
3  Institute for Laboratory and Transfusion Medicine, HDZ NRW Ruhr-University Bochum, Bad Oeynhausen, Germany
,
Simone Lindau
4  Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt, Germany
,
5  Centre for Thrombosis and Haemostasis, University Medical Centre, Johannes Gutenberg University Mainz, Mainz, Germany
6  University Medical Centre, Johannes Gutenberg University Mainz, Germany
,
Oliver Grottke
7  Department of Anaesthesiology, RWTH Aachen University Hospital, Aachen, Germany
,
Ulrike Nowak-Göttl
8  Clinical Chemistry, Univ. Hospital Schleswig-Holstein, Kiel, Germany
9  The Israel National Hemophilia Centre, Sheba Medical Center, Tel Hashomer, Israel
,
Jessica Lucks
10  Coagulation Research Center, Cardioangiologisches Centrum Bethanien, Frankfurt, Germany (Ringgold ID: RIN542202)
,
Barbara Zydek
10  Coagulation Research Center, Cardioangiologisches Centrum Bethanien, Frankfurt, Germany (Ringgold ID: RIN542202)
,
Christian von Heymann
11  Vivantes Klinikum im Friedrichshain, Berlin, Germany (Ringgold ID: RIN27695)
,
Ariane Sümnig
12  Department of Immunology and Transfusion Medicine, Universitätsmedizin, Greifswald, Greifswald, Germany
,
Jan Beyer-Westendorf
13  Thrombosis Research Unit, Department of Medicine I, Division Hematology, University Hospital “Carl Gustav Carus”, Dresden, Germany
,
Sebastian Schellong
14  Municipal Hospital of Dresden-Friedrichstadt, Dresden, Germany
,
Patrick Meybohm
4  Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt, Germany
15  Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Wuerzburg, Wuerzburg, Germany
,
Andreas Greinacher
16  Department of Immunology and Transfusion Medicine, Universitätsmedizin Greifswald, Greifswald, Germany
,
Eva Herrmann
17  Med. Klinik III, Johann-Wolfgang-Goethe-Universitätsklinik Frankfurt, Frankfurt, Germany
› Author Affiliations
Supported by: Bayer HealthCare
Supported by: Daiichi Sankyo Company
Supported by: CSL Behring
Supported by: Bristol-Myers Squibb/Pfizer

Clinical Trials Registration: Reversal Agent use in patients treated with Direct Oral Anticoagulants or vitamin K antagonists Registry (RADOA-registry) https://clinicaltrials.gov/ct2/show/NCT01722786?term=lindhoff-last&rank=9 ClinicalTrials.gov Identifier: NCT01722786

Background Direct oral anticoagulants (DOAC) are increasingly used worldwide. Little is known so far about their pharmacokinetics in emergency situations. Methods A prospective, observational registry was performed to determine the clinical course in consecutive patients with major bleeding or urgent surgery treated with DOACs. In back-up blood samples from routine care DOAC drug concentrations were measured using UPLC-MS/MS. Anticoagulant intensity at first presentation and drug half-life (t1/2), tested in repeat samples, were evaluated. Results 140 patients were prospectively included. Pharmacokinetic data were available in 94% (132/140) of patients. 67% (89/132) experienced life-threatening bleeding and 33% (43/132) needed an urgent surgery. For pharmacokinetic analysis a total of 605 blood samples was available. Median concentration on admission was 205 ng/mL for rivaroxaban and 108 ng/mL for apixaban. All treatment groups showed a high variation of drug concentrations at baseline. In rivaroxaban treated patients t½ was 17.3 hours (95% CI: 15.4 – 19.7) without significant difference in both groups (major bleeding: t½ 16.7 hours, 95% CI: 14.7 - 19.3; urgent surgery: t½ 19.7 hours, 95% CI 15.2 - 27.9; p=0.292). In apixaban treated patients t½ was 25.0 hours (95% CI: 22.9 – 27.6) with a longer t½ after urgent surgery (t1/2: 30.8 hours; 95% CI: 26.9 – 36.4) compared to severe bleeding (t1/2: 20.8 hours; 95% CI: 18.8 – 23.2; p<0.001). Conclusions Emergency patients under DOAC treatment show a high variation of anticoagulant concentrations at baseline. Compared with rivaroxaban, apixaban showed a lower median concentration on admission and a longer t½.



Publication History

Received: 19 March 2021

Accepted after revision: 25 June 2021

Publication Date:
13 July 2021 (online)

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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