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

Author:

Harenberg JobORCID,Gosselin Robert C.1ORCID,Cuker Adam2ORCID,Becattini Cecilia3ORCID,Pabinger Ingrid4ORCID,Poli SvenORCID,Weitz JeffreyORCID,Ageno Walter5ORCID,Bauersachs Rupert6ORCID,Celap IvanaORCID,Choi PhilipORCID,Douketis James7ORCID,Douxfils JonathanORCID,Elalamy IsmailORCID,Falanga AnnaORCID,Fareed Jawed8ORCID,Favaloro Emmanuel J.ORCID,Gerotziafas GrigoriosORCID,Herkner Harald9ORCID,Hetjens Svetlana10ORCID,Heubner Lars11ORCID,Klamroth Robert12ORCID,Langer Forian13ORCID,Lip Gregory Y. H.ORCID,Grory Brian Mac14ORCID,Margetić SandraORCID,Merrelaar Anne9ORCID,Pikta MarikaORCID,Renne ThomasORCID,Schulman SamORCID,Schwameis Michael9ORCID,Strbian Daniel15ORCID,Tafur AlfonsoORCID,Vassart Julie16ORCID,Violi Francesco17ORCID,Walenga Jeanine18ORCID,Weiss Christel10ORCID

Affiliation:

1. Davis Health System, Thrombosis and Hemostasis Center, University of California, Sacramento, California, United States

2. Department of Medicine and Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States

3. Internal and Emergency Medicine -Stroke Unit, University of Perugia, Perugia PG, Italy

4. Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria

5. Department of Medicine and Surgery, University of Insubria, Varese, Italy

6. GefasCentrum, CCB - Cardioangiologisches Centrum Bethanien, Frankfurt am Main, Germany

7. Department Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada

8. Department of Molecular Pharmacology & Neuroscience, Loyola University Medical Center, Maywood, Illinois, United States

9. Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria

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

11. Department of Anesthesiology and Intensive Care Medicine, University Hospital “Carl Gustav Carus,” Technische Universitat Dresden, Germany

12. Vascular Medicine and Haemostaseology, Vivantes Klinikum im Friedrichschain, Berlin, Germany

13. II. Medizinische Klinik und Poliklinik, Universitatsklinikum Eppendorf, Hamburg, Germany

14. Department of Neurology, Duke University, Durham, North Carolina, United States

15. Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland

16. Department of Pharmacy, Namur Research for Life Sciences, Namur, Belgium

17. Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy

18. Cardiovascular Research Institute, Loyola University Chicago, Maywood, Illinois, United States

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.

Publisher

Georg Thieme Verlag KG

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