Accuracy of a Rapid Diagnostic Test for the Presence of Direct Oral Factor Xa or Thrombin Inhibitors in Urine—A Multicenter Trial

Job Harenberg; Jan Beyer-Westendorf; Mark Crowther; Jonathan Douxfils; Ismail Elalamy; Peter Verhamme; Rupert Bauersachs; Svetlana Hetjens; Christel Weiss; Working Group Members

doi:10.1055/s-0039-1700545

Thrombosis and Haemostasis, Inhaltsverzeichnis

CC BY-NC-ND 4.0 · Thromb Haemost 2020; 120(01): 132-140
DOI: 10.1055/s-0039-1700545

New Technologies, Diagnostic Tools and Drugs

Georg Thieme Verlag KG Stuttgart · New York

Accuracy of a Rapid Diagnostic Test for the Presence of Direct Oral Factor Xa or Thrombin Inhibitors in Urine—A Multicenter Trial

Job Harenberg

¹DOASENSE GmbH, Heidelberg, Germany

²Ruprecht Karls University of Heidelberg, Heidelberg, Germany

,

Jan Beyer-Westendorf

³Division Hematology, Thrombosis Research Unit, Department of Medicine I, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany

⁴Department of Haematology, King's College London, London, United Kingdom

,

Mark Crowther

⁵Thrombosis and Atherosclerosis Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada

,

Jonathan Douxfils

⁶Department of Pharmacy, Namur Thrombosis and Hemostasis Centre, Namur Research Institute for Life Sciences, University of Namur, Namur, Belgium

⁷QUALIblood, Namur, Belgium

,

Ismail Elalamy

⁸Service d'Hématologie Biologique Hôpital Tenon, Hôpitaux Universitaires Est Parisien, Assistance Publique Hôpitaux de Paris, Paris, France

⁹Department of Obstetrics and Gynecology, The First I.M. Sechenov Moscow State Medical University, Moscow, Russia

,

Peter Verhamme

¹⁰Department of Cardiovascular Sciences, Vascular Medicine and Haemostasis, University of Leuven, Leuven, Belgium

,

Rupert Bauersachs

¹¹Department of Vascular Medicine, Klinikum Darmstadt GmbH, Darmstadt, Germany

,

Svetlana Hetjens

¹²Department of Statistics, Medical Faculty Mannheim, Ruprecht Karls University of Heidelberg, Mannheim, Germany

,

Christel Weiss

¹²Department of Statistics, Medical Faculty Mannheim, Ruprecht Karls University of Heidelberg, Mannheim, Germany

,

Working Group Members

(

Ingo Ahrens

¹³Köln, Klinik für Kardiologie und internistische Intensivmedizin

,

Timo Bömicke

¹³Köln, Klinik für Kardiologie und internistische Intensivmedizin

,

Rupert Bauersachs

¹⁴Coburg, II. Medizinische Klinik-Innere Medizin-Kardiologie, Darmstadt, Klinik für Gefäßmedizin-Angiologie

,

Jörg Herold

¹⁴Coburg, II. Medizinische Klinik-Innere Medizin-Kardiologie, Darmstadt, Klinik für Gefäßmedizin-Angiologie

,

Jan Beyer-Westendorf

¹⁵Dresden, Studienambulanz Klinische Thromboseforschung

,

Sandra Marten

¹⁵Dresden, Studienambulanz Klinische Thromboseforschung

,

Christiane Naue

¹⁵Dresden, Studienambulanz Klinische Thromboseforschung

,

Harald Darius

¹⁶Berlin, Vivantes Klinikum Neukölln, Kardiologie

,

Lorenz Reill

¹⁶Berlin, Vivantes Klinikum Neukölln, Kardiologie

,

Daniel Dürschmied

¹⁷Freiburg, Klinik für Kardiologie und Angiologie I

,

Roland Giesen

¹⁷Freiburg, Klinik für Kardiologie und Angiologie I

,

Christoph Olivier

¹⁷Freiburg, Klinik für Kardiologie und Angiologie I

,

Martin Grünewald

¹⁸Heidenheim, Facharztpraxis für Innere Medizin, Schwerpunkt Hämatologie, Onkologie und Hämostaseologie

,

Robert Klamroth

¹⁹Berlin, Vivantes Klinikum im Friedrichshain, Zentrum für Gefäßmedizin - Sprechstunde für Gerinnungsstörung und Hämophiliezentrum

,

Cornelia Kubicek-Hofmann

¹⁹Berlin, Vivantes Klinikum im Friedrichshain, Zentrum für Gefäßmedizin - Sprechstunde für Gerinnungsstörung und Hämophiliezentrum

,

AnaMarija Orlovic

¹⁹Berlin, Vivantes Klinikum im Friedrichshain, Zentrum für Gefäßmedizin - Sprechstunde für Gerinnungsstörung und Hämophiliezentrum

,

Florian Langer

²⁰Hamburg, Onkologisches Zentrum, II. Medizinische Klinik und Poliklinik, Gerinnungsambulanz

,

Minna Voigtländer

²⁰Hamburg, Onkologisches Zentrum, II. Medizinische Klinik und Poliklinik, Gerinnungsambulanz

,

Edelgard Lindhoff-Last

²¹Frankfurt, CCB Studienzentrum GmbH

,

Barbara Zydek

²¹Frankfurt, CCB Studienzentrum GmbH

,

Frank Menzel

²²Dessau-Roßlau, Praxis für Innere Medizin, Kardiologie, Angiologie

,

Cornelia Piper

²³Bad Oeynhausen, Herz - und Diabeteszentrum NRW, Klinik für Kardiologie

,

Isgandarova Potratz

²³Bad Oeynhausen, Herz - und Diabeteszentrum NRW, Klinik für Kardiologie

,

Sebastian Schellong

²⁴Dresden, Studienambulanz der GWT-TUD GmbH

,

Carsten Müller

²⁴Dresden, Studienambulanz der GWT-TUD GmbH

,

Ute Scholz

²⁵Leipzig, Zentrum für Blutgerinnungsstörungen

,

Michael Krause

²⁵Leipzig, Zentrum für Blutgerinnungsstörungen

,

Christoph Sucker

²⁶Berlin, Gerinnungszentrum Berlin

,

Dietmar Trenk

²⁷Bad Krozingen, Universitätsherzzentrum, Klinik für Kardiologie und Angiologie II

,

Julia Hromek

²⁷Bad Krozingen, Universitätsherzzentrum, Klinik für Kardiologie und Angiologie II

,

Stefan Leggewie

²⁷Bad Krozingen, Universitätsherzzentrum, Klinik für Kardiologie und Angiologie II

,

Ulrich Overhoff

²⁸Siegen, Zentrum für Prävention und Rehabilitation

,

Fabian Krämer

²⁸Siegen, Zentrum für Prävention und Rehabilitation

,

Ulrich Wolf

²⁹Stahnsdorf, Parkkardiologie

)› Institutsangaben

Abstract

The rapid determination of the presence of direct oral anticoagulants (DOACs) in a patient remains a major challenge in emergency medicine and for rapid medical treatment decisions. All DOACs are excreted into urine. A sensitive and specific point-of-care test has been developed to determine whether they are present in patient urine samples. This prospective multicenter study aimed to demonstrate at least 95% correct positive and negative predictive results for factor Xa and thrombin inhibitors in urine samples using DOAC Dipstick pads compared with liquid chromatography-tandem mass spectrometry (LC-MS/MS) (NCT03182829). Nine hundred and fourteen subjects were included and 880 were evaluated per protocol (factor Xa inhibitors apixaban, edoxaban, and rivaroxaban: n = 451, thrombin inhibitor dabigatran: n = 429) at 18 centers. The sensitivity, specificity, accuracy, and predictive values and agreement between methods for determination of factor Xa inhibitors were at least noninferior to 95% with a 0.5% margin and of thrombin inhibitor superior to 97.5%. These results were compared with LC-MS/MS results in the intention-to-analyze cohort (all p < 0.05). The receiver operating curve showed c-values of 0.989 (factor Xa inhibitors) and 0.995 (thrombin inhibitor). Visual evaluation of the factor Xa and thrombin inhibitor pads was not different between centers. Qualitative determination of both types of DOACs was accurate using the DOAC Dipstick compared with using LC-MS/MS. The high predictive values may impact laboratory and clinical decision-making processes.

Keywords

direct oral anticoagulants - point-of-care test - apixaban - edoxaban - rivaroxaban - dabigatran

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Referenzen

References
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