Evaluation of the DOAC-Stop® Procedure to Overcome the Effect of DOACs on Several Thrombophilia Screening Tests
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Abstract The impact of direct oral anticoagulants (DOACs) on laboratory assays used for thrombophilia testing (e.g., antithrombin, protein S, protein C, lupus anticoagulant and activated protein-C resistance) is a well-known issue and may cause false-positive and -negative results. Therefore, the correct interpretation of tests that are performed in patients taking DOACs is mandatory to prevent misclassification and the subsequent clinical consequences. We aimed at evaluating the efficiency of a new and simple procedure (DOAC-Stop®; Haematex Research, Hornsby, Australia) to overcome the effect of all DOACs in real-life settings and to assess the percentage of erroneous results due to the presence of DOACs on thrombophilia screening tests. For this purpose, 135 DOAC-treated patients (38 apixaban, 40 dabigatran, 15 edoxaban, and 42 rivaroxaban) and 20 control patients were enrolled. A significant drop in apixaban, dabigatran, edoxaban, and rivaroxaban plasma concentrations following the DOAC-Stop® treatment was observed (74.8–8.2 ng/mL [p < 0.0001], 95.9–4.7 ng/mL [p < 0.0001], 102.1–8.8 ng/mL [p = 0.001], and 111.3–7.0 ng/mL [p < 0.0001], respectively). The DOAC-Stop® treatment was mostly effective to overcome the effect of DOACs on PTT-LA, dilute Russell's viper venom time (dRVVT) screen, and dRVVT confirm tests. Using our procedures, false-positive results due to DOACs were observed only with lupus anticoagulant tests (up to 75%) and fell to zero after the DOAC-Stop® procedure, regardless of the DOAC considered. In conclusion, the DOAC-Stop® adsorbent procedure appeared to be an effective and simple way to overcome the interference of DOAC on coagulation tests and should facilitate the interpretation of thrombophilia screening tests in patients taking DOACs.
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Pretreatment with adsorbents may alter clotting times, producing false-positive or false-negative LA results or incomplete removal of direct oral anticoagulants.
“Several studies indicated that pretreatment with adsorbents may affect clotting times resulting in false-positive or false-negative LA results, or incomplete removal of DOACs.33,[41][42][43]”
From Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis (2020) · cites this paper as [42]
The DOAC-Stop® Treatment section (page unavailable) says the adsorbent minimally affected aPTT and PT in samples without DOACs. It does not show adsorbent-induced false-positive or false-negative LA results: the Results report that false-positive LA results fell to zero after treatment and residual DOAC levels were below assay quantification limits. The Discussion notes that LA-positive patients were not included, limiting what the study can say about false negatives. (LLM, conf=0.84)
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Cites
Update of the guidelines for lupus anticoagulant detection
PENGO, V., TRIPODI, A., REBER, G., RAND, J. H., ORTEL, T. L., GALLI, M., & DE GROOT, P. G. (2009) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2009.03555.x · Cited by 1,197 · see citing works
Biological Variation: From Principles to Practice
Fraser, C. G. (2001) · Cited by 653 · see citing works
Thrombophilia Testing and Venous Thrombosis
Connors, J. M. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1700365 · Cited by 413 · see citing works
Douxfils, J., Ageno, W., Samama, C. M., Lessire, S., Cate, H. T., Verhamme, P. B., Dogné, J.-M., & Mullier, F. (2017) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.13912 · Cited by 384 · see citing works
Self-citationImpact of dabigatran on a large panel of routine or specific coagulation assays
Robert, S., Chatelain, C., Douxfils, J., Mullier, F., Châtelain, B., & Dogné, J. (2012) · Thrombosis and Haemostasis · doi:10.1160/th11-11-0804 · Cited by 322 · see citing works
Self-citationEffects of the oral, direct factor Xa inhibitor rivaroxaban on commonly used coagulation assays
Hillarp, A., Baghaei, F., Fagerberg, I., Gustafsson, K. M., Stigendal, L., Sten-Linder, M., Strandberg, K., & Lindahl, T. L. (2010) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2010.04098.x · Cited by 287 · see citing works
Testa, S., Tripodi, A., Legnani, C., Pengo, V., Abbate, R., Dellanoce, C., Carraro, P., Salomone, L., Paniccia, R., Paoletti, O., et al. (2015) · Thrombosis Research · doi:10.1016/j.thromres.2015.12.001 · Cited by 187 · see citing works
Direct Oral Anticoagulants (DOACs) in the Laboratory: 2015 Review
Adcock, D. M., & Gosselin, R. C. (2015) · Thrombosis Research · doi:10.1016/j.thromres.2015.05.001 · Cited by 166 · see citing works
Gosselin, R. C., Grant, R. P., & Adcock, D. M. (2016) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.12528 · Cited by 124 · see citing works
Assessment of apixaban plasma levels by laboratory tests: suitability of three anti-Xa assays
Flaujac, C., Delavenne, X., Quenet, S., Horellou, M., Laporte, S., Siguret, V., Lecompte, T., & Gouin‐Thibault, I. (2013) · Thrombosis and Haemostasis · doi:10.1160/th13-06-0470 · Cited by 115 · see citing works
Dufrost, V., Risse, J., Zuily, S., & Wahl, D. G. (2016) · Current Rheumatology Reports · doi:10.1007/s11926-016-0623-7 · Cited by 99 · see citing works
Detection of lupus anticoagulant in the presence of rivaroxaban using Taipan snake venom time
OS, G. M. A. V., de Laat, B., Kamphuisen, P. W., Meijers, J. C. M., & de Groot, P. G. (2011) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2011.04395.x · Cited by 87 · see citing works
Simple method for removing DOACs from plasma samples
Exner, T., Michalopoulos, N., Pearce, J., et al. (2018) · Thrombosis Research · doi:10.1016/j.thromres.2018.01.047 · Cited by 81 · see citing works
Edoxaban: Impact on routine and specific coagulation assays
Châtelain, B., Chatelain, C., Douxfils, J., Dogné, J., & Mullier, F. (2015) · Thrombosis and Haemostasis · doi:10.1160/th15-05-0415 · Cited by 77 · see citing works
Self-citationDetection of lupus anticoagulant in the era of direct oral anticoagulants
Hoxha, A., Banzato, A., Ruffatti, A., & Pengo, V. (2016) · Autoimmunity Reviews · doi:10.1016/j.autrev.2016.12.010 · Cited by 74 · see citing works
Thrombophilia Testing and Venous Thrombosis
Goodwin, A. J., IV, & Adcock, D. M. (2017) · New England Journal of Medicine · doi:10.1056/nejmc1713797 · Cited by 62 · see citing works
Arachchillage, D. J., Mackie, I. J., Efthymiou, M., Isenberg, D. A., Machin, S. J., & Cohen, H. (2015) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.12917 · Cited by 60 · see citing works
Activated protein C resistance testing for factor V L eiden
Kadauke, S., Khor, B., & Cott, E. M. V. (2014) · American Journal of Hematology · doi:10.1002/ajh.23867 · Cited by 54 · see citing works
The use of direct oral anticoagulants in 56 patients with antiphospholipid syndrome
Malec, K., Góralczyk, T., & Undas, A. (2016) · Thrombosis Research · doi:10.1016/j.thromres.2016.12.009 · Cited by 53 · see citing works
Comparison of Methods to Determine Rivaroxaban anti-factor Xa activity
Rathbun, S. W., Tafur, A. J., Grant, R. P., et al. (2014) · Thrombosis Research · doi:10.1016/j.thromres.2014.11.017 · Cited by 48 · see citing works
de Maat, M. P. M., van Schie, M. C., Kluft, C., Leebeek, F. W. G., & Meijer, P. (2016) · Clinical Chemistry · doi:10.1373/clinchem.2016.261248 · Cited by 47 · see citing works
Effects of Direct Oral Anticoagulants on Lupus Anticoagulant Assays in a Real-Life Setting
Antovic, A., Norberg, E.-M., Berndtsson, M., Rasmuson, A., Malmström, R. E., Skeppholm, M., & Antovic, J. (2017) · Thrombosis and Haemostasis · doi:10.1160/th17-03-0204 · Cited by 46 · see citing works
Direct oral anticoagulants in antiphospholipid syndrome: a real life case series
Betancur, J., Bonilla‐Abadía, F., Hormaza-Jaramillo, A., et al. (2016) · Lupus · doi:10.1177/0961203315624555 · Cited by 44 · see citing works
Jacquemin, M. G., Toelen, J., Schoeters, J., Horenbeeck, I. V., Vanlinthout, I., Debasse, M., Peetermans, M., Vanassche, T., Peerlinck, K., van Ryn, J., et al. (2015) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.13138 · Cited by 37 · see citing works
Direct oral anticoagulants in hypercoagulable states
Kunk, P. R., Brown, J. T., McShane, M., Palkimas, S., & Macik, B. G. (2016) · Journal of Thrombosis and Thrombolysis · doi:10.1007/s11239-016-1420-x · Cited by 35 · see citing works
Jacquemin, M. G., Toelen, J., Feyen, L., Schoeters, J., Horenbeeck, I. V., Vanlinthout, I., Debasse, M., Vanassche, T., Peerlinck, K., & Verhamme, P. B. (2018) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.12807 · Cited by 33 · see citing works
Wilmer, M., Stocker, C., Bühler, B., et al. (2004) · American Journal of Clinical Pathology · doi:10.1309/t8av-vh7q-wgl0-qtf5 · Cited by 30 · see citing works
Blerk, M. V., Bailleul, E., Châtelain, B., et al. (2017) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.12640 · Cited by 30 · see citing works
Wilmer, M., Stöcker, C., Bühler, B., et al. (2004) · American Journal of Clinical Pathology · doi:10.1309/t8avvh7qwgl0qtf5 · Cited by 26 · see citing works
Lupus Anticoagulant Testing: Diluted Russell Viper Venom Time (dRVVT)
Pengo, V., Bison, E., Banzato, A., Zoppellaro, G., Jose, S. P., & Denas, G. (2017) · Methods in Molecular Biology · doi:10.1007/978-1-4939-7196-1_14 · Cited by 21 · see citing works
Pouplard, C., Vayne, C., Berthomet, C., Guéry, E., Delahousse, B., & Gruel, Y. (2016) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.12611 · Cited by 16 · see citing works
Thrombophilia testing in patients taking direct oral anticoagulants. Handle with care
Lippi, G., Mattiuzzi, C., & Favaloro, E. J. (2014) · Diagnosis · doi:10.1515/dx-2014-0054 · Cited by 15 · see citing works
Cini, M., Legnani, C., Cosmi, B., et al. (2018) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.12772 · Cited by 14 · see citing works
Shou, W., Chen, Q., Wu, W., et al. (2015) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0035-1552588 · Cited by 11 · see citing works
Gessoni, G., Valverde, S., Valle, L., et al. (2017) · PubMed · doi:10.2450/2017.0199-16 · Cited by 10 · see citing works
Gessoni, G., Valverde, S., Valle, L., et al. (2017) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.12647 · Cited by 5 · see citing works
Herve, T., Beaufils, S., Kochan, J. P., et al. (2014) · Blood · doi:10.1182/blood.v124.21.2870.2870 · Cited by 4 · see citing works
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Steffel, J., Collins, R., Antz, M., Cornu, P., Desteghe, L., Haeusler, K. G., Oldgren, J., Reinecke, H., Roldan-Schilling, V., Rowell, N., et al. (2021) · EP Europace · doi:10.1093/europace/euab065 · Cited by 1,132 · see citing works
Devreese, K. M. J., de Groot, P. G., de Laat, B., Erkan, D., Favaloro, E. J., Mackie, I., Martinuzzo, M., Ortel, T. L., Pengo, V., Rand, J. H., et al. (2020) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.15047 · Cited by 439 · see citing works
Cohen, H., Mackie, I. J., & Devreese, K. M. J. (2019) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.14560 · Cited by 48 · see citing works
De Kesel, P. M. M., & Devreese, K. M. J. (2020) · Research and Practice in Thrombosis and Haemostasis · doi:10.1002/rth2.12264 · Cited by 47 · see citing works
- Authors
- Favresse, J., Lardinois, B., Sabor, L., Devalet, B., Vandepapeliere, J., Braibant, M., Lessire, S., Chatelain, B., Jacqmin, H., Douxfils, J., & Mullier, F.
- Affiliations
- Namur Research Institute for Life Sciences (BE)
- UCLouvain (BE)
- Université Catholique de Louvain, CHU UCL Namur, Hematology Laboratory, Namur Thrombosis and Hemostasis Center, NARILIS, Yvoir, Belgium
- University of Namur (BE)
- Corresponding author
- Mullier, François
- ORCID
- Venue
- TH Open
- Publisher
- Georg Thieme Verlag KG
- Published
- 2018-04
- Volume
- 02
- Issue
- 02
- Pages
- e202-e209
- ISSN
- 2512-9465 (ISSN-L)
- PMC
- PMC6524876
- OpenAlex
- W2805959260
- Cited by
- 73
- References
- 37
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 5 · 2022: 7 · 2021: 17 · 2020: 18 · 2019: 12 · 2018: 1
- FWCI
- 8.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- TH Open (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Repository of the University of Namur (publishedVersion, cc-by-nc-nd)
- Digital Access to Libraries (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Keywords
- direct oral anticoagulants, thrombophilia screening, antithrombin III, protein S, protein C, lupus anticoagulant, activated protein C resistance, apixaban, dabigatran, edoxaban, rivaroxaban, plasma adsorption, false positives, coagulation tests, dilute Russell's viper venom time
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