CC BY-NC-ND 4.0 · Thromb Haemost
DOI: 10.1055/s-0039-1700545
Original Article
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
1  DOASENSE GmbH, Heidelberg, Germany
2  Ruprecht Karls University of Heidelberg, Heidelberg, Germany
,
Jan Beyer-Westendorf
3  Division Hematology, Thrombosis Research Unit, Department of Medicine I, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
4  Department of Haematology, King's College London, London, United Kingdom
,
Mark Crowther
5  Thrombosis and Atherosclerosis Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
,
Jonathan Douxfils
6  Department of Pharmacy, Namur Thrombosis and Hemostasis Centre, Namur Research Institute for Life Sciences, University of Namur, Namur, Belgium
7  QUALIblood, Namur, Belgium
,
Ismail Elalamy
8  Service d'Hématologie Biologique Hôpital Tenon, Hôpitaux Universitaires Est Parisien, Assistance Publique Hôpitaux de Paris, Paris, France
9  Department of Obstetrics and Gynecology, The First I.M. Sechenov Moscow State Medical University, Moscow, Russia
,
Peter Verhamme
10  Department of Cardiovascular Sciences, Vascular Medicine and Haemostasis, University of Leuven, Leuven, Belgium
,
Rupert Bauersachs
11  Department of Vascular Medicine, Klinikum Darmstadt GmbH, Darmstadt, Germany
,
Svetlana Hetjens
12  Department of Statistics, Medical Faculty Mannheim, Ruprecht Karls University of Heidelberg, Mannheim, Germany
,
Christel Weiss
12  Department of Statistics, Medical Faculty Mannheim, Ruprecht Karls University of Heidelberg, Mannheim, Germany
› Author Affiliations
Further Information

Publication History

14 August 2019

07 September 2019

Publication Date:
08 November 2019 (online)

  

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.

Participating Centers (alphabetical order per town, number of included patients in brackets)

Bad Krozingen, Universitätsherzzentrum, Klinik für Kardiologie und Angiologie II, Prof. Dr. Dietmar Trenk, Prof. Dr. Julia Hromek, Dr. Stefan Leggewie (n = 232); Bad Oeynhausen, Herz - und Diabeteszentrum NRW, Klinik für Kardiologie, Prof. Dr. Cornelia Piper, Dr. Isgandarova Potratz (n = 79); Berlin, Vivantes Klinikum Neukölln, Kardiologie, Prof. Dr. Harald Darius, Dr. Lorenz Reill (n = 36); Berlin, Vivantes Klinikum im Friedrichshain, Zentrum für Gefäßmedizin - Sprechstunde für Gerinnungsstörung und Hämophiliezentrum, Priv. Doz Dr. Robert Klamroth, Dr. Cornelia Kubicek-Hofmann, Dr. Ana Marija Orlovic (n = 27); Berlin, Gerinnungszentrum Berlin, Priv.-Doz. Dr . Christoph Sucker (n = 46); Coburg, II. Medizinische Klinik – Innere Medizin – Kardiologie, Dr. Steffen Schnupp, Dr. Issameddine Ajimi, Dr. Christian Mahnkopf, Dr. Thomas Mischke (n = 70); Darmstadt, Klinik für Gefäßmedizin - Angiologie, Prof. Dr Rupert Bauersachs, Priv. Doz. Dr. Jörg Herold (n = 18); Dessau-Roßlau, Praxis für Innere Medizin, Kardiologie, Angiologie, Dr. Frank Menzel, Frank (n = 41); Dresden, Studienambulanz Klinische Thromboseforschung, Priv. Doz. Dr. Jan Beyer-Westendorf, Dr. Sandra Marten, Dr. Christiane Naue (n = 3); Dresden, Studienambulanz der GWT – TUD GmbH, Prof. Dr. Sebastian Schellong, Dr. Carsten Müller (n = 12); Frankfurt, CCB Studienzentrum GmbH, Prof. Dr. Edelgard Lindhoff-Last, Dr. Barbara Zydek (n = 89); Freiburg, Klinik für Kardiologie und Angiologie I, Prof. Dr Daniel Dürschmied, Dr. Roland Giesen, Dr. Christoph Olivier (n = 12); Hamburg, Onkologisches Zentrum, II. Medizinische Klinik und Poliklinik, Gerinnungsambulanz, Prof. Dr. Florian Langer, Dr. Minna Voigtländer, (n = 16); Heidenheim, Facharztpraxis für Innere Medizin, Schwerpunkt Hämatologie, Onkologie und Hämostaseologie, Priv. Doz. Dr. Martin Grünewald (n = 14); Köln, Klinik für Kardiologie und internistische Intensivmedizin, Prof. Dr. Ingo Ahrens, Ingo, Dr. Timo Bömicke (n = 2); Leipzig, Zentrum für Blutgerinnungsstörungen, Dr. Ute Scholz, Dr. Michael Krause (n = 18); Stahnsdorf, Parkkardiologie, Dr. Ulrich Wolf (n = 129); Siegen, Zentrum für Prävention und Rehabilitation, Dr. Ulrich Overhoff, Dr. Fabian Krämer (n = 68).


Supplementary Material