Interpretation of normal plasma mixing studies in the laboratory diagnosis of lupus anticoagulants
Abstract
Introduction Mixing studies are part of the laboratory diagnosis of lupus anticoagulants (LA). They are used to determine the evidence of an inhibitor by demonstrating persistence of an abnormal clotting time by mixing patient plasma with normal plasma. Since there is no standardised interpretation of results of mixing studies, percent correction formulas are proposed. The sensitivity of mixing studies strongly depends on the interpretation of the results. Materials and methods A retrospective analysis was performed on 361 samples, 75 LA-positive and 286 LA-negative samples. For all the LA-positive samples and for 181/286 LA-negative samples mixing tests on one or more screening tests were performed. A percent correction formula and the Rosner index were calculated for all mixing tests on aPTT and dPT. Results The Conclusions This study demonstrates that the Rosner index and the percent correction formulas for interpretation of mixing studies are complementary and can help to reduce misclassification of LA-positive or LA-negative samples.
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Mixing tests may make weak LA samples appear negative due to a dilution factor.
“mixing plasma with NPP shows a dilution factor that can make weaker LA samples appear negative in the mixing test despite clear positivity in the screening and confirmation results on undiluted plasma”
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 [105]
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
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
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
Evaluation of Different Mixing Study Reagents and Dilution Effect in Lupus Anticoagulant Testing
Kaczor, D. A., Bickford, N. N., & Triplett, D. A. (1991) · American Journal of Clinical Pathology · doi:10.1093/ajcp/95.3.408 · Cited by 46 · cited 2× · see citing works
“Samples were taken and stored as recommended [7—9].”
MethodNormal 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
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Antiphospholipid 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-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-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
Kumano, O., & Moore, G. W. (2018) · Research and Practice in Thrombosis and Haemostasis · doi:10.1002/rth2.12069 · Cited by 26 · see citing works
Pradella, P., Azzarini, G., Santarossa, L., Caberlotto, L., Bardin, C., Poz, A., D’Aurizio, F., & Giacomello, R. (2013) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2012-0382 · 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
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
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
“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].”
BackgroundLupus 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
“This corresponded to 10-year prospective ATE, VTE, and overall thrombosis incidences of 14% (95%CI: 9-21), 20% (13-28), and 34% (26-43), respectively, and a 10-year mortality of 14% (9-22) (supplemental Figure 2).”
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
- Authors
- Devreese, K. M. J.
- Affiliations
- Ghent University Hospital (BE)
- Corresponding author
- Devreese, Katrien M.J.
- Venue
- Thrombosis Research
- Publisher
- Elsevier BV
- Published
- 2007-01
- Volume
- 119
- Issue
- 3
- Pages
- 369-376
- ISSN
- 0049-3848 (ISSN-L)
- OpenAlex
- W2015162021
- Cited by
- 46
- References
- 5
- Citations by year
- 2026: 5 · 2023: 4 · 2022: 5 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 3
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Thrombosis Research (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, activated partial thromboplastin time, diagnostic sensitivity
- MeSH terms
- Humans, Partial Thromboplastin Time, Predictive Value of Tests, Retrospective Studies, Thrombosis, Lupus Coagulation Inhibitor
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