Influence of anticardiolipin and anti‐β2 glycoprotein I antibody cutoff values on antiphospholipid syndrome classification
Open accessAbstract
BACKGROUND: Anticardiolipin (aCL) and anti-β2 glycoprotein I (aβ2GPI) immunoglobulin (Ig) G/IgM antibodies are 2 of the 3 laboratory criteria for classification of antiphospholipid syndrome (APS). The threshold for clinically relevant levels of antiphospholipid antibodies (aPL) for the diagnosis of APS remains a matter of debate. The aim of this study was to evaluate the variation in cutoffs as determined in different clinical laboratories based on the results of a questionnaire as well as to determine the optimal method for cutoff establishment based on a clinical approach. METHODS: The study included samples from 114 patients with thrombotic APS, 138 patients with non-APS thrombosis, 138 patients with autoimmune disease, and 183 healthy controls. aCL and aβ2GPI IgG/IgM antibodies were measured at 1 laboratory using 4 commercial assays. Assay-specific cutoff values for aPL were obtained by determining 95th and 99th percentiles of 120 compared to 200 normal controls by different statistical methods. RESULTS: Normal reference value data showed a nonparametric distribution. Higher cutoff values were found when calculated as 99th rather than 95th percentiles. These values also showed a stronger association with thrombosis. The use of 99th percentile cutoffs reduced the chance of false positivity but at the same time reduced sensitivity. The decrease in sensitivity was higher than the gain in specificity when 99th percentiles were calculated by methods wherein no outliers were eliminated. CONCLUSIONS: We present cutoff values for aPL determined by different statistical methods. The 99th percentile cutoff value seemed more specific. However, our findings indicate the need for standardized statistical criteria to calculate 99th percentile cutoff reference values.
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From a statistical viewpoint, the minimum sample size for an appropriate estimate of the 99th centile is at least 300.
“From a statistical viewpoint, as illustrated for aCL and aβ2GPI antibodies, the minimum sample size for an appropriate estimation of the 99th centile is at least 300.69”
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- Authors
- Vanoverschelde, L., Kelchtermans, H., Musial, J., de Laat, B., & Devreese, K. M. J.
- Affiliations
- Ghent University Hospital (BE)
- Maastricht University (NL)
- Corresponding author
- Devreese, Katrien M.J.
- Venue
- Research and Practice in Thrombosis and Haemostasis
- Publisher
- Elsevier BV
- Published
- 2019-07
- Volume
- 3
- Issue
- 3
- Pages
- 515-527
- ISSN
- 2475-0379 (ISSN-L)
- PMC
- PMC6611479
- OpenAlex
- W2947464917
- Cited by
- 33
- References
- 25
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 1
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Research and Practice in Thrombosis and Haemostasis (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Homo Politicus (Academy of Humanities and Economics in Lodz) (submittedVersion, cc-by-nc-nd)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by-nc-nd)
- Research Publications (Maastricht University) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- Bio-Rad Laboratories
- 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
- antiphospholipid syndrome, anticardiolipin antibodies, anti-beta2-glycoprotein I antibodies, thrombotic antiphospholipid syndrome, false positivity, sensitivity and specificity, reference values, assay standardization
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