Lupus anticoagulant assay cut‐offs vary between reagents even when derived from a common set of normal donor plasmas
Open accessAbstract
Background Multicenter studies reveal that diagnostic efficacy of lupus anticoagulant (LA) assays is enhanced if cut-offs are locally generated. However, a potential confounder is the inevitable use of separate normal donor populations.Objectives Generate cut-offs for multiple LA reagents with the same analyzer and normal donor plasmas.Methods Cut-offs for screen ratio, confirm ratio, percent correction of screen ratio by confirm ratio, and normalized screen/confirm ratio (NSCR) were derived from the same 50 normal donor plasmas for screen and confirm pairs for two dilute Russell's viper venom time reagents, LA1/LA2 and HEMOCLOT™ LA-S/LA-C, and two APTTs, Actin FSL/FS and Cephen LS/Cephen. The cut-offs were challenged with plasmas from 20 triple-positive APS patients and 25 plasmas from LA-negative, thrombotic patients.Results Cut-offs for screen ratio, confirm ratio, percent correction, and NSCR, respectively, were 1.12/1.08/8.3/1.09 for LA1/LA2; 1.17/1.10/13.6/1.13 for HEMOCLOT™ LA-S/LA-C; 1.12/1.13/9.7/1.10 for Actin FSL/FS; 1.09/1.13/11.0/1.11 for Cephen LS/Cephen. LA1 and LA-S screens were elevated in 19/20 and 16/20 triple-positive plasmas, respectively, while 20/20 were detected with both via integrated interpretation ie, percent correction or NSCR irrespective of screen elevation. Actin FSL and Cephen LS screens were elevated in 17/20 and 19/20 triple-positive plasmas, respectively, while one more LA was detected with Actin FSL via integrated interpretation, but not for Cephen LS. Integrated interpretation suggested 5/25 LA-negative plasmas contained weak LA (two with Actin FSL/FS, two with LA1/LA2, one with LA-S/LA-R).Conclusions Employing the same normal donor plasmas and analytical platform does not compensate for between-reagent differences when generating LA assay cut-offs.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Another study found poor agreement of cutoff values across laboratories even when different platforms tested the same normal donor set.
“A more recent study showed poor interlaboratory agreement of cutoff value even when a common set of normal donors were investigated by different platforms.78”
Evidence shows that there is great inter-laboratory variability even when using the same analytic platform.
“even if evidence shows that there is a great inter-laboratory variability even when using the same analytic platform [61,63].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [63]
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
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
Self-citationClinical course of high‐risk patients diagnosed with antiphospholipid syndrome
PENGO, V., RUFFATTI, A., LEGNANI, C., GRESELE, P., BARCELLONA, D., ERBA, N., TESTA, S., MARONGIU, F., BISON, E., DENAS, G., et al. (2010) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2009.03674.x · Cited by 633 · 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
Laboratory criteria for antiphospholipid syndrome: communication from the SSC of the ISTH
Devreese, K. M. J., Ortel, T. L., Pengo, V., & de Laat, B. (2018) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.13976 · Cited by 269 · see citing works
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
Self-citationLaboratory Testing for Lupus Anticoagulants: A Review of Issues Affecting Results
Tripodi, A. (2007) · Clinical Chemistry · doi:10.1373/clinchem.2007.089524 · Cited by 81 · see citing works
Machin, S., Giddings, J. C., Greaves, M., Hutton, R. A., Mackie, J. D., Malía, R. G., Taberner, D. A., Davidson, J. F., Barrowcliffe, T. W., Kernoff, B., et al. (1991) · Journal of Clinical Pathology · doi:10.1136/jcp.44.11.885 · Cited by 80 · see citing works
Biasiolo, A., Rampazzo, P., Brocco, T., & Pengo, V. (1999) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1614453 · Cited by 76 · see citing works
Mackie, I. J., Purdy, G., Machin, S. J., & Lawrie, A. S. (1999) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1614567 · Cited by 75 · see citing works
Gardiner, 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
Cohen, H., Mackie, I. J., & Devreese, K. M. J. (2019) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.14560 · Cited by 48 · see citing works
Toulon, P. A., Eloit, Y., Smahi, M., Sigaud, C., Jambou, D., Fischer, F., & Appert‐Flory, A. (2016) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.12499 · Cited by 43 · see citing works
Tripodi, A., Chantarangkul, V., Cini, M., Devreese, K., Dlott, J. S., Giacomello, R., Gray, E., Legnani, C., Martinuzzo, M. E., Pradella, P., et al. (2017) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.13678 · Cited by 35 · see citing works
Laboratory methods to detect antiphospholipid antibodies
Krilis, S. A., & Giannakopoulos, B. (2014) · Hematology · doi:10.1182/asheducation-2014.1.321 · Cited by 30 · see citing works
Lupus anticoagulant detection: out of control?
Moore, G. W., Brown, K. L., Bromidge, E. S., Drew, A. J., & Ledford‐Kraemer, M. R. (2013) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.12006 · Cited by 27 · see citing works
Self-citationPradella, 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. (2018) · Research and Practice in Thrombosis and Haemostasis · doi:10.1002/rth2.12069 · Cited by 26 · see citing works
Self-citationFalse negative screening tests for lupus anticoagulants—An unrecognized problem?
Jacobsen, E. M., & Wislöff, F. (1996) · Thrombosis Research · doi:10.1016/0049-3848(96)00094-1 · Cited by 24 · 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
Self-citationAchieving and maintaining quality in the laboratory
Hertzberg, M., Mammen, J., MCCRAW, A., et al. (2006) · Haemophilia · doi:10.1111/j.1365-2516.2006.01278.x · Cited by 20 · 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
Gerbutavičius, R., Fareed, J., Messmore, H. L., Iqbal, O., Hoppensteadt, D. A., Wehrmacher, W. H., Demir, M., Piccolo, P., Ahmad, S., Ma, Q., et al. (2002) · Clinical and Applied Thrombosis/Hemostasis · doi:10.1177/107602960200800206 · Cited by 14 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Devreese, K. M. J., Bertolaccini, M. L., Branch, D. W., de Laat, B., Erkan, D., Favaloro, E. J., Pengo, V., Ortel, T. L., Wahl, D., & Cohen, H. (2025) · Journal of Thrombosis and Haemostasis · doi:10.1016/j.jtha.2024.10.022 · Cited by 92 · see citing works
Moore, 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-citationLupus 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
“These guidelines also consider the possibility of acquiring cut-offs established in other laboratories, even if evidence shows that there is a great inter-laboratory variability even when using the same analytic platform [61,63].”
BackgroundChantarangkul, V., Peyvandi, F., & Tripodi, A. (2020) · Thrombosis Research · doi:10.1016/j.thromres.2020.03.018 · Cited by 8 · 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
Self-citationLupus Anticoagulant Testing in Challenging Situations: Navigating Complexities
Devreese, K. M. J. (2026) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.14490 · Cited by 2 · see citing works
- Authors
- Moore, G. W., & Kumano, O.
- Affiliations
- St Thomas' Hospital (GB)
- Sysmex (Japan) (JP)
- Corresponding author
- Moore, Gary W.
- Venue
- Journal of Thrombosis and Haemostasis
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 18
- Issue
- 2
- Pages
- 439-444
- ISSN
- 1538-7836 (ISSN-L)
- OpenAlex
- W2982390432
- Cited by
- 18
- References
- 24
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 5 · 2022: 2 · 2021: 2 · 2020: 4
- FWCI
- 1.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Thrombosis and Haemostasis (publishedVersion)
- 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, Russell's viper venom time, activated partial thromboplastin time, antiphospholipid syndrome, integrated interpretation, thrombosis, reagent comparison
- MeSH terms
- Blood Coagulation Tests, Humans, Indicators and Reagents, Partial Thromboplastin Time, Prothrombin Time, Lupus Coagulation Inhibitor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
