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Cited by 20Systemic Lupus Erythematosus ResearchBlood Coagulation and Thrombosis MechanismsClinical Laboratory Practices and Quality Control

Application of different lupus anticoagulant diagnostic algorithms to the same assay data leads to interpretive discrepancies in some samples

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Moore, Gary W., Maloney, James C., de Jager, Naomi, Dunsmore, Clare L., Gorman, Dervilla K., Polgrean, Richard F., Bertolaccini, Maria L.·2017·Research and Practice in Thrombosis and Haemostasis
DOI 10.1002/rth2.12006PMC PMC6058200
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Abstract

BACKGROUND: Gold standard lupus anticoagulant (LA) assays and reference plasmas do not exist and detection is based on inference in a medley of coagulation assays, creating potential for interpretive discrepancies when applying different algorithms. OBJECTIVES: To investigate discrepancies from applying different algorithms to a common data set. METHODS: Diagnostic data on 311 non-anticoagulated patients LA-positive by dilute Russell's viper venom time (dRVVT) and/or dilute activated partial thromboplastin time (dAPTT) assays were employed to compare algorithms. Routine testing applied interpretive criteria from guidelines endorsing classification as LA-positive despite negative mixing tests, after exclusion of other clotting abnormalities. Integrated testing without mixing tests, and the classical algorithm where negative mixing tests preclude confirm tests, were then retrospectively applied to those data. RESULTS: Initial testing showed 92/311 (29.6%) were LA-positive by dRVVT only, 156/311 (50.1%) by dAPTT only, and 63/311 (20.3%) by both assays. All dAPTT-positive plasmas remained positive with integrated testing but eight dRVVT-positives became negative. Other data suggested they were false-negatives. The classical algorithm altered 52/155 (33.5%) dRVVT and 111/219 (50.7%) dAPTT interpretations to LA-negative because of normal mixing tests, most of which were apparently weak LA in undiluted plasma. CONCLUSIONS: The classical algorithm improves diagnostic specificity and confidence but risks missing some genuine LA due to false-negative mixing tests. Integrated testing can be diagnostically accurate and logistically efficient but oversimplifies complex cases. Performing mix and confirm in response to an elevated screen with their interpretation based on clinical data, coagulation screens and the LA-assay design offers a potentially valuable option.

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  • False-negative mixing tests can arise from reagent sensitivity and specificity to LA; some LAs that are positive in screening tests with both aPTT and dRVVT show positivity in the mixing test for one test but not the other.

    “False-negatives mixing tests can also arise for reasons other than dilution, such as reagents’ sensitivity and specificity to LA: some LAs, undoubtedly positive in screening tests with both aPTT and dRVVT, show positivity in the mixing for one test but not for the other [105,106].”

    From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [106]

    The Results and Discussion (page unavailable) report different false-negative mixing-test rates for dRVVT and dAPTT and identify reagent composition as a possible contributor to mixing-test results beyond antibody potency. The paper does not establish that samples positive on both screening tests were mixing-test positive on one assay but negative on the other, or that reagent sensitivity and specificity caused that particular pattern. (LLM, conf=0.82)

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  • There is currently no established gold standard assay or reference plasma for LA detection.

    “As a result, there are currently no established gold standard assays or reference plasmas for LA detection [[6], [7], [8], [9], [10]].”

    From Comparison of different algorithms for lupus anticoagulant detection: a single-center experience (2024) · cites this paper as [7]

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Cited by

Sorted by citations

Authors
Moore, G. W., Maloney, J. C., de Jager, N., Dunsmore, C. L., Gorman, D. K., Polgrean, R. F., & Bertolaccini, M. L.
Affiliations
St Thomas' Hospital (GB)
Corresponding author
Moore, Gary W.
ORCID
Moore, Gary W.
Venue
Research and Practice in Thrombosis and Haemostasis
Publisher
Elsevier BV
Published
2017-07
Volume
1
Issue
1
Pages
62-68
ISSN
2475-0379 (ISSN-L)
DOI
10.1002/rth2.12006
PMC
PMC6058200
OpenAlex
W2669292274
Cited by
20
References
5
Citations by year
2026: 2 · 2025: 1 · 2024: 4 · 2023: 6 · 2022: 2 · 2021: 2 · 2019: 2 · 2017: 1
FWCI
0.72
Type
journal article
Language
en
Open access
Licence
Locations
  • Research and Practice in Thrombosis and Haemostasis (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
  • Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
Keywords
lupus anticoagulant, diagnostic algorithm, dilute Russell's viper venom time, mixing test, confirmatory testing, false-negative results, diagnostic specificity, anticoagulant screening

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