Clinical significance of the mixing test in laboratory diagnoses of lupus anticoagulant
Abstract
The mixing test is used to determine the presence of inhibitors in laboratory diagnoses of lupus anticoagulant. Updated international guidelines state that an integrated lupus anticoagulant test system does not require the mixing test; an appraisal of the mixing tests in integrated lupus anticoagulant test systems is, therefore, required. We investigated the clinical relevance of mixing tests by using the best cutoff value of the mixing test through thrombotic risk analysis. A retrospective analysis was performed on 525 specimens with positive screening tests by using two integrated lupus anticoagulant tests: diluted Russell's Viper venom (dRVVT) and silica clotting time. The diagnostic performance of two interpretation formulas (percentage correction, Rosner index) was assessed, and the thrombotic risk of a subgroup based on the mixing results was investigated. Finally, the thrombotic risk of lupus anticoagulant positivity based on the integrated lupus anticoagulant test system procedures was assessed for the appraisal of mixing test exclusion in integrated lupus anticoagulant test systems. The best cutoff values of mixing test interpretation methods based on dRVVT were as follows: 60.1% for percentage correction and 15.7 for Rosner index. There was no substantial difference in the thrombotic risk between percentage correction and the Rosner index. The mixing-positive group showed a higher lupus anticoagulant titer and higher thrombotic risk than the mixing-negative group. H…
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The mixing of weak LA samples may introduce loss of detectable LA activity and false-negativity give rise to inaccurate interpretation if the mixing test result is employed as a decision point for subsequent confirmatory test performance.
“The mixing of weak LA samples may introduce loss of detectable LA activity and the false‐negativity give rise to inaccurate interpretation if the mixing test result is employed as a decision point for subsequent confirmatory test performance.14, 31, 32, 33”
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
Levine, J. S., Branch, D. W., & Rauch, J. (2002) · New England Journal of Medicine · doi:10.1056/nejmra002974 · Cited by 1,524 · 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
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
Guidelines On The Investigation and Management Of The Antiphospholipid Syndrome
Greaves, M., Cohen, H., Machin, S. J., & Mackie, I. J. (2000) · British Journal of Haematology · doi:10.1046/j.1365-2141.2000.02069.x · Cited by 294 · see citing works
Survey of lupus anticoagulant diagnosis by central evaluation of positive plasma samples
Pengo, V., Biasiolo, A., Gresele, P., Marongiu, F., Erba, N., Veschi, F., Ghirarduzzi, A., Candia, E. D., Montaruli, B., Testa, S., et al. (2007) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2007.02454.x · Cited by 95 · see citing works
Laboratory diagnosis of the antiphospholipid syndrome
Wislöff, F., Jacobsen, E. M., & Liestøl, S. (2002) · Thrombosis Research · doi:10.1016/s0049-3848(02)00400-0 · Cited by 92 · see citing works
Jennings, I., Greaves, M., Mackie, I. J., Kitchen, S., Woods, T. A. L., Preston, F. E., & ation, O. B. O. T. U. N. E. Q. A. S. F. B. C. (2002) · British Journal of Haematology · doi:10.1046/j.1365-2141.2002.03821.x · Cited by 72 · see citing works
A “Percent Correction” Formula for Evaluation of Mixing Studies
Chang, S.-H., Tillema, V., & Scherr, D. (2002) · American Journal of Clinical Pathology · doi:10.1309/rrek-8l6m-d2kc-hwlh · Cited by 67 · see citing works
Interpretation of normal plasma mixing studies in the laboratory diagnosis of lupus anticoagulants
Devreese, K. M. J. (2007) · Thrombosis Research · doi:10.1016/j.thromres.2006.03.012 · Cited by 46 · see citing works
Moore, G. W., & Savidge, G. F. (2006) · Thrombosis Research · doi:10.1016/j.thromres.2005.09.010 · Cited by 46 · see citing works
DEVREESE, K. M. J. (2010) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2010.03807.x · Cited by 42 · see citing works
Normal plasma mixing studies in the laboratory diagnosis of lupus anticoagulant
Thom, J., Ivey, L., & Eikelboom, J. (2003) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2003.0543h.x · Cited by 39 · see citing works
Ledford-Kraemer, M. (2008) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0028-1085481 · Cited by 20 · see citing works
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Recent 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
“29,50,51,62,63 Detection of weaker LAs is a particular advantage of this approach, where the prolongation of a patient ’ s basal clotting time is insuf fi cient to exceed the upper reference limit of a screening test, yet the screen and con fi rm discrepancy reveals the antibody.”
BackgroundInfluentialMixing 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
Moore, 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
Kumano, 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., Ieko, M., Naito, S., Yoshida, M., Takahashi, N., Suzuki, T., & Aoki, T. (2014) · Thrombosis Research · doi:10.1016/j.thromres.2014.05.030 · Cited by 15 · see citing works
Favaloro, E. J., Bonar, R., & Marsden, K. (2013) · Blood Coagulation & Fibrinolysis · doi:10.1097/mbc.0b013e328360c71b · Cited by 14 · see citing works
Kumano, O., Ieko, M., Naito, S., Yoshida, M., Takahashi, N., & Aoki, T. (2013) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.12345 · Cited by 14 · see citing works
Analytical 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
- Hong, S. K., Hwang, S. M., Kim, J.-E., & Kim, H. K.
- Affiliations
- Seoul National University (KR)
- Corresponding author
- Kim, Ji-Eun
- Kim, Hyun Kyung
- Venue
- Blood Coagulation & Fibrinolysis
- Published
- 2012-12
- Volume
- 23
- Issue
- 8
- Pages
- 739-744
- ISSN
- 0957-5235 (ISSN-L)
- OpenAlex
- W2331915197
- Cited by
- 22
- References
- 16
- Citations by year
- 2025: 1 · 2023: 2 · 2022: 3 · 2017: 5 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 4
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood Coagulation & Fibrinolysis (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, mixing test, thrombosis risk, diagnostic thresholds
- MeSH terms
- Adult, Female, Humans, Male, Middle Aged, Partial Thromboplastin Time, Predictive Value of Tests, Prothrombin Time, Retrospective Studies, Risk Factors, Thrombosis, Lupus Coagulation Inhibitor, Antiphospholipid Syndrome, Practice Guidelines as Topic
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