Testing for Lupus Anticoagulants
Abstract
Lupus anticoagulant (LA) is one of the three criteria antiphospholipid antibodies (aPLs) employed in classification, and by default diagnosis, of antiphospholipid syndrome (APS). Detection of LA is not via calibrated assays but is based on functional behavior of the antibodies in a medley of coagulation assays. A prolonged clotting time in a screening test is followed by demonstration of phospholipid dependence and inhibitory properties in confirmatory and mixing tests, respectively, which are modifications of the parent screening test. Complications arise because no single screening test is sensitive to every LA, and no test is specific for LA, because they are prone to interference by other causes of elevated clotting times. Several screening tests are available but the pairing of dilute Russell's viper venom time (dRVVT) with LA-sensitive activated partial thromboplastin time (aPTT) is widely used and recommended because it is proven to have good detection rates. Nonetheless, judicious use of other assays can improve diagnostic performance, such as dilute prothrombin time to find LA unreactive with dRVVT and aPTT, and the recently validated Taipan snake venom time with ecarin time confirmatory test that are unaffected by vitamin K antagonist and direct factor Xa inhibitor anticoagulation. Expert body guidelines and their updates have improved harmonization of laboratory practices, although some issues continue to attract debate, such as the place of mixing tests in the med…
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Because of the in vitro competition between LA and coagulation factors for phospholipid-binding sites, the phospholipidic component of the screening test is importantly diluted to accentuate the inhibitory effect of any LA antibody present.
“Because of the in vitro competition between LA and coagulation factors for phospholipid-binding sites, the phospholipidic component of the test is importantly diluted to accentuate the inhibitory effect of any LA antibody present [25].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [25]
Clotting times of screening, mixing, and confirmatory procedures are prone to inter- and intra-assay variability; therefore, it is recommended to normalize these clotting times by generating a ratio between test clotting time and NPP clotting time.
“Clotting times of screening, mixing, and confirmatory procedures are prone to inter- (between same-principle tests offered by different manufacturers) and intra-assay (between batches of the same reagent) variability [25]; for this reason, it is recommended to normalize a screening, mixing, and confirmatory clotting time, generating a ratio between test clotting time and NPP clotting time [9,36,48”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [25]
The heterogeneity of LA antibodies and the variability of their effect in coagulation assays explain why there is not a single test sensitive to all LA, and a combination of several assays is necessary for correct diagnosis.
“The heterogeneity of these antibodies and the variability of the effect they provoke in several coagulation assays explain why there is not a single test that is sensitive to all the LA, but it is necessary to use a combination of several assays for a correct diagnosis [25].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [25]
All assays for LA detection, except those employing snake-venom-derived prothrombin activators, are affected by DOACs.
“All the assays for LA detection, except those employing snake-venom-derived prothrombin activators, are affected by DOACs [25].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [25]
The second approach (CLSI/BSH parametric) moves toward a balance between sensitivity and specificity.
“The second approach moves toward a balance between sensitivity and specificity [25].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [25]
All assays for LA detection, except those employing snake-venom-derived prothrombin activators, are affected by VKA.
“All the assays for LA detection, except those employing snake-venom-derived prothrombin activators, are affected by VKA [25].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [25]
Cites
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Recent Guidelines and Recommendations for Laboratory Detection of Lupus Anticoagulants
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Mixing studies in lupus anticoagulant testing are required at least in some type of samples
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Self-citationEvaluation of Different Mixing Study Reagents and Dilution Effect in Lupus Anticoagulant Testing
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Current Controversies in Lupus Anticoagulant Detection
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Self-citationTesting for lupus anticoagulants–fresh or frozen?
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Lupus 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
“…on clotting time prolongation is evidenced by calculating the percent correction of the screening by the confirmatory procedure: %Correction = [(CT screening − CT confirm )/CT screening ] × 100 If percent correction is higher than the cut-off, the result is indicative of the presence of LA [8,25].”
BackgroundMethodInfluentialMoore, G. W., Foxton, E., Platton, S., Yartey, N., White, D., & MacDonald, S. G. (2023) · Journal of Thrombosis and Haemostasis · doi:10.1016/j.jtha.2023.08.009 · Cited by 6 · see citing works
Self-citationAnalytical dilemmas in lupus anticoagulant detection
Moore, G. W. (2023) · Exploration of Immunology · doi:10.37349/ei.2023.00104 · Cited by 5 · see citing works
Self-citationViewpoint: 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
- Moore, G. W.
- Affiliations
- Cambridge University Hospitals NHS Foundation Trust (GB)
- Corresponding author
- Moore, Gary W.
- ORCID
- Moore, Gary W.
- Venue
- Seminars in Thrombosis and Hemostasis
- Publisher
- Georg Thieme Verlag KG
- Published
- 2022-06-01
- Volume
- 48
- Issue
- 06
- Pages
- 643-660
- ISSN
- 0094-6176 (ISSN-L)
- 1098-9064
- OpenAlex
- W4281699009
- Cited by
- 30
- References
- 17
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 11 · 2023: 6 · 2022: 3
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Seminars in Thrombosis and Hemostasis (publishedVersion)
- PubMed (publishedVersion)
- 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, antiphospholipid syndrome, antiphospholipid antibodies, dilute Russell's viper venom time, activated partial thromboplastin time, mixing test, phospholipid dependence, laboratory diagnosis
- MeSH terms
- Anticoagulants, Blood Coagulation Tests, Humans, Partial Thromboplastin Time, Phospholipids, Prothrombin Time, Vitamin K, Lupus Coagulation Inhibitor, Antiphospholipid Syndrome, Antibodies, Antiphospholipid, Factor Xa Inhibitors
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