No more mixing tests required for integrated assay systems in the laboratory diagnosis of lupus anticoagulants?
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Omitting the mixing step may produce false-positive and false-negative LA results.
“More recent studies illustrate that omitting the mixing step may give false-positive and false-negative results.35,58,60”
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 [58]
In the paper’s main text (indexed under Abstract; page unavailable), omitting mixing tests yielded many more LA-positive classifications, supporting concern about false positives. The paper does not support the attributed false-negative risk from omission: it says weak LA may instead test falsely negative when patient plasma is diluted for a mixing test. (LLM, conf=0.88)
Experimental — accuracy not yet measuredInformation from the confirmatory test can aid interpretation even when the mixing step is negative.
“However, information on the confirmatory test, even if the mixing step is negative, can help in the interpretation.34,35,58”
Potency alone does not necessarily correlate with clinical significance and thrombotic risk.
“On the other hand, a number of studies have indicated populations of clinically significant LA despite the negative results in the mixing tests14, 32, 36 and the potency alone does not necessarily correlate with clinical significance and thrombotic risk.37, 39”
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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
Brandt, J. T., Triplett, D. A., Alving, B. M., & Scharrer, I. (1995) · PubMed · Cited by 1,164 · see citing works
Brandt, J. T., Triplett, D. A., Alving, B., & Scharrer, I. (1995) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1649901 · Cited by 993 · see citing works
Detection and Quantitative Evaluation of Lupus Circulating Anticoagulant Activity
Rosner, E., Pauzner, R., Lusky, A., Modan, M., & Many, A. (1987) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1651083 · Cited by 188 · see citing works
A Hexagonal (II) Phase Phospholipid Neutralization Assay for Lupus Anticoagulant Identification
Triplett, D. A., Barna, L. K., & Unger, G. A. (1993) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1649671 · Cited by 132 · see citing works
Devreese, K., Peerlinck, K., & Hoylaerts, M. F. (2010) · Blood · doi:10.1182/blood-2009-09-244426 · Cited by 93 · see citing works
Self-citationLaboratory diagnosis of the antiphospholipid syndrome: a plethora of obstacles to overcome
Devreese, K., & Hoylaerts, M. F. (2009) · European Journal Of Haematology · doi:10.1111/j.1600-0609.2009.01243.x · Cited by 78 · see citing works
Self-citationGardiner, C., Mackie, I. J., Malía, R. G., Jones, D. W., Winter, M. R., Leeming, D., Taberner, D. A., Machin, S. J., & Greaves, M. (2000) · British Journal of Haematology · doi:10.1046/j.1365-2141.2000.02466.x · Cited by 55 · see citing works
Moore, G. W. (2007) · Thrombosis Journal · doi:10.1186/1477-9560-5-12 · Cited by 32 · see citing works
Further evidence of false negative screening for lupus anticoagulants
Moore, G. W., Henley, A., Greenwood, C. K., & Rangarajan, S. (2007) · Thrombosis Research · doi:10.1016/j.thromres.2007.05.018 · Cited by 21 · see citing works
Gardiner, C., Mackie, I. J., Malía, R. G., et al. (2000) · British Journal of Haematology · doi:10.1111/j.1365-2141.2000.02466.x · Cited by 18 · 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-citationRecent Guidelines and Recommendations for Laboratory Detection of Lupus Anticoagulants
Moore, G. (2014) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0033-1364185 · Cited by 148 · see citing works
“48,51 However, the possibility of a coexisting or alternative abnormality must be considered, and performance of both screen and con fi rm on 1:1 mixtures with NPP can aid discriminating between potent LA, LA þ coexisting abnormality, or non-LA abnormality.”
BackgroundInfluentialAntiphospholipid antibody testing and standardization
Devreese, K. M. J. (2014) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.12234 · Cited by 98 · see citing works
Self-citationMixing 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., Jones, P. O., Platton, S., Hussain, N., White, D., Thomas, W., Rigano, J., Pouplard, C., Gray, E., & Devreese, K. M. J. (2021) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.15438 · Cited by 47 · see citing works
Self-citationMoore, G. W., Culhane, A. P., Daw, C. R., Noronha, C. P., & Kumano, O. (2016) · Thrombosis Research · doi:10.1016/j.thromres.2016.01.019 · Cited by 42 · see citing works
Current 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
Clinical significance of the mixing test in laboratory diagnoses of lupus anticoagulant
Hong, S. K., Hwang, S. M., Kim, J.-E., & Kim, H. K. (2012) · Blood Coagulation & Fibrinolysis · doi:10.1097/mbc.0b013e328358e899 · Cited by 22 · 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-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
- Authors
- DEVREESE, K. M. J.
- Affiliations
- Ghent University Hospital (BE)
- Corresponding author
- DEVREESE, K.M.J.
- ORCID
- DEVREESE, K.M.J.
- Venue
- Journal of Thrombosis and Haemostasis
- Publisher
- Elsevier BV
- Published
- 2010-05
- Volume
- 8
- Issue
- 5
- Pages
- 1120-1122
- ISSN
- 1538-7836 (ISSN-L)
- OpenAlex
- W1974787410
- Cited by
- 42
- References
- 12
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 4 · 2014: 3 · 2013: 2 · 2012: 1
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Thrombosis and Haemostasis (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- 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, mixing test, laboratory diagnosis, coagulation tests, order errors, pre-analytical errors, post-analytical errors
- MeSH terms
- Humans, Lupus Coagulation Inhibitor, Clinical Laboratory Techniques
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