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Thromb Haemost
DOI: 10.1055/a-2261-1811
New Technologies, Diagnostic Tools and Drugs

Algorithm for Rapid Exclusion of Clinically Relevant Plasma Levels of Direct Oral Anticoagulants in Patients Using the DOAC Dipstick: An Expert Consensus Paper

Job Harenberg 
1   Ruprecht Karls University of Heidelberg, Heidelberg, Germany
2   DOASENSE GmbH, Heidelberg, Germany
,
Robert C. Gosselin 
3   Davis Health System, Thrombosis and Hemostasis Center, University of California, Sacramento, California, United States
,
Adam Cuker 
4   Department of Medicine and Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
,
Cecilia Becattini 
5   Internal and Emergency Medicine -Stroke Unit, University of Perugia, Perugia PG, Italy
,
Ingrid Pabinger 
6   Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
,
Sven Poli 
7   Department of Neurology & Stroke, Eberhard-Karls University, University Hospital, Tubingen, Germany
8   Hertie Institute for Clinical Brain Research, Eberhard-Karls University, Tubingen, Germany
,
Jeffrey Weitz 
9   Department of Medicine, McMaster University, Hamilton, Ontario, Canada
10   Department Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada
,
Walter Ageno 
11   Department of Medicine and Surgery, University of Insubria, Varese, Italy
,
Rupert Bauersachs 
12   GefasCentrum, CCB - Cardioangiologisches Centrum Bethanien, Frankfurt am Main, Germany
,
Ivana Celap 
13   Department of Clinical Chemistry, University Hospital Center Sestre, Zagreb, Croatia
14   Faculty of Pharmacy and Biochemistry, University of Zagreb, Croatia
,
Philip Choi 
15   Neurosciences, Box Hill Hospital, Eastern Health, Melbourne, Victoria, Australia
16   Eastern Health Clinical School, Monash University, Australia
,
James Douketis 
10   Department Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada
,
Jonathan Douxfils 
17   Department of Pharmacy, Namur Research for Life Sciences, Namur, Belgium
18   Qualiblood s.a., Department of Research and Development, Namur, Belgium
,
Ismail Elalamy 
19   Service d'Hematologie Biologique Hopital Tenon, Hopitaux Universitaires Est Parisien, Assistance Publique Hopitaux de Paris, Paris, France
20   Department of Obstetrics and Gynecology, The First I.M. Sechenov Moscow State Medical University, Moscow, Russia
,
Anna Falanga 
21   Department of Transfusion Medicine and Hematology, Hospital Papa Giovanni XXIII, Bergamo, Italy
22   University of Milan Bicocca, Monza, Italy
,
Jawed Fareed 
23   Department of Molecular Pharmacology & Neuroscience, Loyola University Medical Center, Maywood, Illinois, United States
,
Emmanuel J. Favaloro 
24   Department of Haematology, Sydney Centres for Thrombosis and Haemostasis, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Westmead, NSW, Australia
25   Faculty of Science and Health, Charles Sturt University, Wagga Wagga, NSW, Australia
,
Grigorios Gerotziafas 
26   INSERM, UMR_S 938, Research Group Cancer, Biology and Therapeutics, Centre de recherche Saint-Antoine (CRSA), Institut Universitaire de Cancerologie, Sorbonne Universite, Paris, France
27   Thrombosis Center, Tenon-Saint Antoine, Hopitaux Universitaires de l'Est Parisien, Assistance Publique Hopitaux de Paris (APHP), France
,
Harald Herkner 
28   Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria
,
Svetlana Hetjens 
29   Department of Statistics, Medical Faculty Mannheim, Ruprecht Karls University of Heidelberg, Mannheim, Germany
,
Lars Heubner 
30   Department of Anesthesiology and Intensive Care Medicine, University Hospital “Carl Gustav Carus,” Technische Universitat Dresden, Germany
,
Robert Klamroth 
31   Vascular Medicine and Haemostaseology, Vivantes Klinikum im Friedrichschain, Berlin, Germany
,
Forian Langer 
32   II. Medizinische Klinik und Poliklinik, Universitatsklinikum Eppendorf, Hamburg, Germany
,
Gregory Y. H. Lip 
33   Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom
34   Danish Center for Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
,
Brian Mac Grory 
35   Department of Neurology, Duke University, Durham, North Carolina, United States
,
Sandra Margetić 
12   GefasCentrum, CCB - Cardioangiologisches Centrum Bethanien, Frankfurt am Main, Germany
36   School of Medicine, Catholic University of Croatia, Zagreb, Croatia
,
Anne Merrelaar 
28   Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria
,
Marika Pikta 
37   Department of Laboratory Medicine, North Estonia Medical Centre, Tallinn, Estonia
38   Department of Health Technologies, Tallinn University of Technology, Tallinn, Estonia
,
Thomas Renne 
39   Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
40   Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland
,
Sam Schulman 
20   Department of Obstetrics and Gynecology, The First I.M. Sechenov Moscow State Medical University, Moscow, Russia
41   Thrombosis and Atherosclerosis Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
,
Michael Schwameis 
28   Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria
,
Daniel Strbian 
42   Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
,
Alfonso Tafur 
43   Department of Medicine, Vascular Medicine, NorthShore University Health System, Evanston, Illinois, United States
44   Pritzker School of Medicine, University of Chicago, Chicago, Illinois, United States
,
Julie Vassart 
17   Department of Pharmacy, Namur Research for Life Sciences, Namur, Belgium
,
Francesco Violi 
45   Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
,
Jeanine Walenga 
46   Cardiovascular Research Institute, Loyola University Chicago, Maywood, Illinois, United States
,
Christel Weiss 
29   Department of Statistics, Medical Faculty Mannheim, Ruprecht Karls University of Heidelberg, Mannheim, Germany
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Abstract

Background With the widespread use of direct oral anticoagulants (DOACs), there is an urgent need for a rapid assay to exclude clinically relevant plasma levels. Accurate and rapid determination of DOAC levels would guide medical decision-making to (1) determine the potential contribution of the DOAC to spontaneous or trauma-induced hemorrhage; (2) identify appropriate candidates for reversal, or (3) optimize the timing of urgent surgery or intervention.

Methods and Results The DOAC Dipstick test uses a disposable strip to identify factor Xa- or thrombin inhibitors in a urine sample. Based on the results of a systematic literature search followed by an analysis of a simple pooling of five retrieved clinical studies, the test strip has a high sensitivity and an acceptably high negative predictive value when compared with levels measured with liquid chromatography tandem mass spectrometry or calibrated chromogenic assays to reliably exclude plasma DOAC concentrations ≥30 ng/mL.

Conclusion Based on these data, a simple algorithm is proposed to enhance medical decision-making in acute care indications useful primarily in hospitals not having readily available quantitative tests and 24/7. This algorithm not only determines DOAC exposure but also differentiates between factor Xa and thrombin inhibitors to better guide clinical management.

Keywords

direct oral anticoagulants - point-of-care tests - urine - plasma - pooled analysis

Authors' Contribution

Conception of the work: initially by J.H., S.H., A.M., M.S., C.W. and a DOAC POCT meeting held on the occasion of the XXIII ISTH congress by all authors. Two-thirds of the authors participated in person and one-third virtually and approved the conception. Acquisition of data: I.C., P.C., H.H., S.H., A.M., M.P., M.S., J.V., C.W. Statistical analysis: H.H., S.H., C.W. Laboratory methods: J.D., J.V., I.C., P.C., A.M., M.S., M.P. Drafting: J.H., R.C.G., A.C., C.B., I.P., S.P., J.W. Reviewing: All authors. Agreement and final approval: All authors.


The review process for this paper was fully handled by Christian Weber, Editor in Chief.


Supplementary Material



Publication History

Received: 07 July 2023

Accepted: 08 December 2023

Accepted Manuscript online:
05 February 2024

Article published online:
08 March 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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