Laboratory testing for lupus anticoagulant (LA) in patients taking direct oral anticoagulants (DOACs): potential for false positives and false negatives
Abstract
We and others have previously highlighted the potential problems with testing of lupus anticoagulants (LA) in patients on anticoagulant therapy, including most recently as related to the direct oral anticoagulants (DOACs). Thus, current DOACs in use (e.g., dabigatran, a direct thrombin inhibitor, and apixaban and rivaroxaban, both direct Xa inhibitors), affect a wide variety of coagulation assays, including those used in LA investigation. The Russell viper venom time (RVVT) assay in particular, key to the investigation of LA, is highly sensitive to DOACs. LA is a marker of thrombophilia, and patients who have had a thrombosis may be placed on a DOAC. Thus, there is a high likelihood that LA testing will be requested on patients whilst they are on DOACs. In the current report, we have assessed data from our facility for the past two and a half years for all LA tests performed by RVVT testing, and have evaluated this data with respect to patient anticoagulant status. In total, there were 7170 test requests for RVVT associated testing during the period of data capture. Most LA-RVVT screen results (5008; ∼70%) were within normal limits, thereby excluding LA by RVVT method in most of the patient cohort. All DOACs led to a prolongation in both RVVT screen and confirm assays. However, rivaroxaban affected the screen more than the confirm, leading to higher RVVT ratios, whereas apixaban affected the confirm more than the screen, leading to lower RVVT ratios. LA testing in the presence of DOACs also led to lower intra-patient consistency in LA test results. We conclude that ex-vivo data appears to confirm the potential for false positive (with rivaroxaban) and potential for false negative (with apixaban) identification of LA in patients on DOAC treatment. We also make some recommendations in regards to such testing.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Anticoagulant therapy is a main confounding factor in LA testing because it prolongs clotting times in phospholipid-dependent assays.
“One of the main confounding factors in LA testing is anticoagulant therapy, prolonging the clotting times in the PL-dependent assays used for LA detection.”
All DOACs prolong dRVVT in screening and confirmatory procedures, with rivaroxaban affecting screening more than confirmatory (increasing potential false positives) and opposite apixaban action (increasing potential false negatives).
“all DOACs prolong dRVVT in screening and confirmatory procedures, with rivaroxaban affecting screening more than confirmatory (increasing potential false positives) and opposite apixaban action (increasing potential false negatives) [73,74,75,76,77,78].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [73]
Cites
MIYAKIS, S., LOCKSHIN, M. D., ATSUMI, T., BRANCH, D. W., BREY, R. L., CERVERA, R., DERKSEN, R. H. W. M., DE GROOT, P. G., KOIKE, T., MERONI, P. L., et al. (2006) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2006.01753.x · Cited by 7,203 · see citing works
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
Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome
Pengo, V., Denas, G., Zoppellaro, G., Jose, S. P., Hoxha, A., Ruffatti, A., Andreoli, L., Tincani, A., Cenci, C., Prisco, D., et al. (2018) · Blood · doi:10.1182/blood-2018-04-848333 · Cited by 822 · see citing works
Guidelines on the investigation and management of antiphospholipid syndrome
Keeling, D., Mackie, I., Moore, G. W., Greer, I. A., Greaves, M., & British Committee for Standards in Haematology (2012) · British Journal of Haematology · doi:10.1111/j.1365-2141.2012.09037.x · Cited by 740 · see citing works
Off-Label Dosing of Non-Vitamin K Antagonist Oral Anticoagulants and Adverse Outcomes
Steinberg, B. A., Shrader, P. J., Thomas, L. E., Ansell, J., Fonarow, G. C., Gersh, B. J., Kowey, P. R., Mahaffey, K. W., Naccarelli, G. V., Reiffel, J. A., et al. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2016.09.966 · Cited by 493 · see citing works
Bonar, R. A., Favaloro, E. J., Mohammed, S., et al. (2015) · Pathology · doi:10.1016/j.pathol.2015.11.025 · Cited by 110 · see citing works
Self-citationLippi, G., & Favaloro, E. J. (2015) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0035-1546827 · Cited by 107 · see citing works
Self-citationSimple 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
Bonar, R. A., Favaloro, E. J., Mohammed, S., Pasalic, L., Sioufi, J., & MARSDEN, K. A. (2015) · Pathology · doi:10.1097/pat.0000000000000252 · Cited by 77 · see citing works
Self-citationFavaloro, E. J., & Wong, R. C. W. (2014) · Pathology · doi:10.1097/pat.0000000000000142 · Cited by 75 · see citing works
Self-citationFavaloro, E. J., Pasalic, L., Curnow, J. L., & Lippi, G. (2017) · Current Drug Metabolism · doi:10.2174/1389200218666170417124035 · Cited by 52 · see citing works
Self-citationPharmacogenetics of vitamin K antagonists: useful or hype?
Lippi, G., Franchini, M., & Favaloro, E. J. (2009) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2009.140 · Cited by 38 · see citing works
Self-citationFavaloro, E. J., Pasalic, L., & Lippi, G. (2017) · Pathology · doi:10.1016/j.pathol.2017.04.011 · Cited by 36 · see citing works
Self-citationBonar, R., & Favaloro, E. J. (2016) · Thrombosis Research · doi:10.1016/j.thromres.2016.12.007 · Cited by 30 · see citing works
Self-citationZolfaghari, S., Frölich, L., Weiß, C., Wehling, M., Wild, P. S., Prochaska, J. H., Beyer‐Westendorf, J., Koscielny, J., Lip, G. Y. H., & Harenberg, J. (2015) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0035-1546467 · Cited by 15 · see citing works
Anticoagulant Therapy: Present and Future
Favaloro, E. J. (2015) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0035-1546828 · Cited by 13 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
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
Self-citationFavaloro, E. J. (2020) · American Journal of Hematology · doi:10.1002/ajh.25669 · Cited by 53 · see citing works
Self-citationDe 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
Gkrouzman, E., Sevim, E., Finik, J., Andrade, D., Pengo, V., Sciascia, S., Tektonidou, M. G., Ugarte, A., Chighizola, C. B., Belmont, H. M., et al. (2021) · The Journal of Rheumatology · doi:10.3899/jrheum.200513 · Cited by 24 · see citing works
Mixing studies for lupus anticoagulant: mostly yes, sometimes no
Favaloro, E. (2020) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2019-1240 · Cited by 20 · see citing works
Self-citationLupus Anticoagulant Detection under the Magnifying Glass
Molinari, A. C., Martini, T., Banov, L., Ierardi, A., Leotta, M., Strangio, A., & Santoro, R. C. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12206654 · Cited by 9 · see citing works
“…can give both false-positive and false-negative results; all DOACs prolong dRVVT in screening and confirmatory procedures, with rivaroxaban affecting screening more than confirmatory (increasing potential false positives) and opposite apixaban action (increasing potential false negatives) [73–78].”
BackgroundViewpoint: Lupus anticoagulant detection and interpretation in antiphospholipid syndrome
Efthymiou, M., Bertolaccini, M. L., & Cohen, H. (2024) · Rheumatology · doi:10.1093/rheumatology/kead623 · Cited by 5 · see citing works
- Authors
- Favaloro, E. J., Mohammed, S., Curnow, J., & Pasalic, L.
- Affiliations
- Westmead Hospital (AU)
- Corresponding author
- Favaloro, Emmanuel J.
- Venue
- Pathology
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 51
- Issue
- 3
- Pages
- 292-300
- ISSN
- 0031-3025 (ISSN-L)
- OpenAlex
- W2910881013
- Cited by
- 67
- References
- 16
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 8 · 2023: 10 · 2022: 6 · 2021: 11 · 2020: 13 · 2019: 8
- FWCI
- 7.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pathology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Keywords
- lupus anticoagulant, direct oral anticoagulants, false positives, false-negative results, rivaroxaban, apixaban, dabigatran, thrombophilia, coagulation tests, anticoagulant interference
- MeSH terms
- Rivaroxaban, Dabigatran, Anticoagulants, Blood Coagulation, Blood Coagulation Tests, False Negative Reactions, False Positive Reactions, Humans, Prothrombin Time, Lupus Coagulation Inhibitor, Antiphospholipid Syndrome, Thrombophilia
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
