Differences in lupus anticoagulant final conclusion through clotting time or Rosner index for mixing test interpretation
Abstract
Background Lupus anticoagulant (LAC) testing includes a screening, mixing and confirmation step. Although recently published guidelines on LAC testing are a useful step towards standardization, a lack of consensus remains whether to express mixing tests in clotting time (CT) or index of circulating anticoagulant (ICA). The influence of anticoagulant therapy, e.g. vitamin K antagonists (VKA) or direct oral anticoagulants (DOAC) on both methods of interpretation remains to be investigated. The objective of this study was to contribute to a simplification and standardization of the LAC three-step interpretation on the level of the mixing test. Methods Samples from 148 consecutive patients with LAC request and prolonged screening step, and 77 samples from patients non-suspicious for LAC treated with VKA (n=37) or DOAC (n=30) were retrospectively evaluated. An activated partial thromboplastin time (aPTT) and dilute Russell's viper venom time (dRVVT) were used for routine LAC testing. The supplemental anticoagulant samples were tested with dRVVT only. We focused on the interpretation differences for mixing tests expressed as CT or ICA and compared the final LAC conclusion within each distinct group of concordant and discordant mixing test results. Results Mixing test interpretation by CT resulted in 10 (dRVVT) and 16 (aPTT) more LAC positive patients compared to interpretation with ICA. Isolated prolonged dRVVT screen mix ICA results were exclusively observed in samples from VKA-tr…
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In a previous study, MTC had higher sensitivity than ICA for detecting in vitro inhibition of LA with a single dAPTT and dRVVT reagent pairing.
“We previously evidenced that MTC was superior to ICA in detecting the in vitro inhibition of LA with a single dilute APTT (activated partial thromboplastin time) and dRVVT (diluted Russell's viper venom time) pairing.”
MTC and ICA can be calculated and employed as interpretation indices for mixing tests.
“In addition, the mixing test–specific cutoff (MTC) and index of circulating anticoagulant (ICA) can be calculated and employed as interpretation indices for the mixing tests [[15], [16], [17], [18], [19]].”
From Comparison of different algorithms for lupus anticoagulant detection: a single-center experience (2024) · cites this paper as [17]
Several studies have recommended the use of MTC over ICA as it offers greater sensitivity in detecting in vitro inhibition of LA.
“For the interpretation of the LA mixing test result, several studies have recommended the use of MTC over ICA as it offers greater sensitivity in detecting in vitro inhibition of LA [[17], [18], [19]].”
From Comparison of different algorithms for lupus anticoagulant detection: a single-center experience (2024) · cites this paper as [17]
ICA has recently been demonstrated to be less sensitive to LA than a mixing-test-specific cut-off expressed as a normalized ratio.
“Nevertheless, ICA, originally developed for LA detection and later exported to the interpretation of other mixing tests in hemostasis [56], has recently been demonstrated to be less sensitive to LA than a mixing-test-specific cut-off expressed as a normalized ratio [57,58,59].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [57]
Cites
Update of the guidelines for lupus anticoagulant detection
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A “Percent Correction” Formula for Evaluation of Mixing Studies
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Mixing studies in lupus anticoagulant testing are required at least in some type of samples
Devreese, K. M. J., & de Laat, B. (2015) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.13020 · Cited by 63 · see citing works
Self-citationMoore, G. W., & Savidge, G. F. (2006) · Thrombosis Research · doi:10.1016/j.thromres.2005.09.010 · Cited by 46 · see citing works
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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-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
Self-citationCurrent Controversies in Lupus Anticoagulant Detection
Moore, G. (2016) · Antibodies · doi:10.3390/antib5040022 · Cited by 36 · see citing works
Dilute Russell's viper venom time reagents in lupus anticoagulant testing: a well‐considered choice
Depreter, B., & Devreese, K. M. J. (2017) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2016-0245 · Cited by 34 · see citing works
Self-citationKumano, O., & Moore, G. W. (2018) · Research and Practice in Thrombosis and Haemostasis · doi:10.1002/rth2.12069 · Cited by 26 · see citing works
Kumano, O., & Moore, G. W. (2019) · Research and Practice in Thrombosis and Haemostasis · doi:10.1002/rth2.12245 · Cited by 24 · see citing works
Mixing studies for lupus anticoagulant: mostly no, sometimes yes
Moore, G. W. (2020) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2019-1248 · Cited by 19 · see citing works
Evaluation of an automated algorithm for interpretation of lupus anticoagulant testing
Florin, L., Desloovere, M., & Devreese, K. M. J. (2019) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.13001 · Cited by 12 · 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
“Nevertheless, ICA, originally developed for LA detection and later exported to the interpretation of other mixing tests in hemostasis [56], has recently been demonstrated to be less sensitive to LA than a mixing-test-specific cut-off expressed as a normalized ratio [57–59].”
BackgroundAnalytical dilemmas in lupus anticoagulant detection
Moore, G. W. (2023) · Exploration of Immunology · doi:10.37349/ei.2023.00104 · Cited by 5 · see citing works
Viewpoint: 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
Lupus anticoagulant test persistence over time and its associations with future thrombotic events
Colling, M. E., Ay, C., Kraemmer, D., Koder, S., Quehenberger, P., Pabinger, I., Posch, F., & Gebhart, J. (2022) · Blood Advances · doi:10.1182/bloodadvances.2021006011 · Cited by 5 · see citing works
Comparison of different algorithms for lupus anticoagulant detection: a single-center experience
Apipongrat, D., Lamool, R., Arnutti, P., Ruangpratheep, C., & Chantkran, W. (2024) · Research and Practice in Thrombosis and Haemostasis · doi:10.1016/j.rpth.2024.102333 · Cited by 4 · see citing works
- Authors
- Depreter, B., & Devreese, K. M. J.
- Affiliations
- Ghent University Hospital (BE)
- Corresponding author
- Devreese, Katrien M.J.
- Venue
- Clinical Chemistry and Laboratory Medicine (CCLM)
- Publisher
- Walter de Gruyter GmbH
- Published
- 2016-01-19
- Volume
- 0
- Issue
- 0
- Pages
- 1511-6
- ISSN
- 1434-6621 (ISSN-L)
- 1437-4331
- OpenAlex
- W2407436473
- Cited by
- 34
- References
- 6
- Citations by year
- 2025: 1 · 2024: 5 · 2023: 7 · 2022: 5 · 2021: 1 · 2020: 2 · 2019: 5 · 2018: 1 · 2017: 5 · 2016: 2
- FWCI
- 4.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Chemistry and Laboratory Medicine (CCLM) (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Surgery › Heparin-Induced Thrombocytopenia and Thrombosis
- Keywords
- lupus anticoagulant, clotting time, dilute Russell's viper venom time, activated partial thromboplastin time, vitamin K antagonists, direct oral anticoagulants, sensitivity and specificity
- MeSH terms
- Anticoagulants, Blood Coagulation Tests, Humans, Partial Thromboplastin Time, Prothrombin Time, Retrospective Studies, Vitamin K, Lupus Coagulation Inhibitor
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