Pharmacokinetics of Direct Oral Anticoagulants in Emergency Situations: Results of the Prospective Observational RADOA-Registry

Edelgard Lindhoff-Last; Ingvild Birschmann; Joachim Kuhn; Simone Lindau; Stavros Konstantinides; Oliver Grottke; Ulrike Nowak-Göttl; Jessica Lucks; Barbara Zydek; Christian von Heymann; Ariane Sümnig; Jan Beyer-Westendorf; Sebastian Schellong; Patrick Meybohm; Andreas Greinacher; Eva Herrmann; On behalf of the RADOA-Registry Investigators (Reversal Agent use in patients treated with Direct Oral Anticoagulants or vitamin K antagonists Registry)

doi:10.1055/a-1549-6556

Thrombosis and Haemostasis, Inhaltsverzeichnis

CC BY-NC-ND 4.0 · Thromb Haemost 2022; 122(04): 552-559
DOI: 10.1055/a-1549-6556

New Technologies, Diagnostic Tools and Drugs

Pharmacokinetics of Direct Oral Anticoagulants in Emergency Situations: Results of the Prospective Observational RADOA-Registry

Authors

Edelgard Lindhoff-Last‡^*

¹Coagulation Centre at the Cardiology Angiology Centre Bethanien Hospital (CCB), Frankfurt, Germany

²Coagulation Research Centre Bethanien Hospital, Frankfurt, Germany
Ingvild Birschmann‡^*

³Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Centre, Ruhr University, Bochum, Germany
Joachim Kuhn

³Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Centre, Ruhr University, Bochum, Germany
Simone Lindau

⁴Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt, Germany
Stavros Konstantinides

⁵Center for Thrombosis and Haemostasis (CTH), Johannes Gutenberg University, Mainz, Germany
Oliver Grottke

⁶Department of Anaesthesiology, RWTH Aachen University Hospital, Aachen, Germany
Ulrike Nowak-Göttl

⁷Institute of Clinical Chemistry, Thrombosis & Haemostasis Treatment Centre, University Hospital, Kiel-Lübeck, Germany
Jessica Lucks

²Coagulation Research Centre Bethanien Hospital, Frankfurt, Germany
Barbara Zydek

²Coagulation Research Centre Bethanien Hospital, Frankfurt, Germany
Christian von Heymann

⁸Department of Anaesthesia, Intensive Care Medicine, Emergency Medicine and Pain Therapy, Vivantes Klinikum im Friedrichshain, Berlin, Germany
Ariane Sümnig

⁹Department of Immunology and Transfusion Medicine, Universitätsmedizin, Greifswald, Germany
Jan Beyer-Westendorf

¹⁰Thrombosis Research Unit, Department of Medicine 1, Dresden, Germany

¹¹Division of Haematology, Dresden University Clinic, Dresden, Germany

¹²Department of Haematology and Oncology, Kings College, London, United Kingdom
Sebastian Schellong

¹³Medical Department 2, Municipal Hospital, Dresden, Germany
Patrick Meybohm

⁴Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt, Germany

¹⁴Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Wuerzburg, Wuerzburg, Germany
Andreas Greinacher

⁹Department of Immunology and Transfusion Medicine, Universitätsmedizin, Greifswald, Germany
Eva Herrmann

¹⁵Institute of Biostatistics and Mathematical Modelling, Goethe University, Frankfurt, Germany

On behalf of the RADOA-Registry Investigators (Reversal Agent use in patients treated with Direct Oral Anticoagulants or vitamin K antagonists Registry)

Abstract

Background Direct oral anticoagulants (DOACs) 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 samples collected as part of routine care DOAC drug concentrations were measured using ultraperformance liquid chromatography-tandem mass spectrometry. Anticoagulant intensity at first presentation and drug half-life (t _1/2), tested in repeat samples, were evaluated.

Results A total of 140 patients were prospectively included. Pharmacokinetic data were available in 94% (132/140) of patients. Note that 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 t _½ was 17.3 hours (95% confidence interval [CI]: 15.4–19.7) without significant difference in both groups (major bleeding: t _½ 16.7 hours, 95% CI: 14.7–19.3; urgent surgery: t _½ 19.7 hours, 95% CI: 15.2–27.9; p = 0.292). In apixaban-treated patients t _½ was 25.0 hours (95% CI: 22.9–27.6) with a longer t _½ after urgent surgery (t _1/2: 30.8 hours; 95% CI: 26.9–36.4) compared with severe bleeding (t _1/2: 20.8 hours; 95% CI: 18.8–23.2; p < 0.001).

Conclusion 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 t _½.

Keywords

direct oral anticoagulants - pharmacokinetics - emergency - major bleeding - urgent surgery

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