Antiphospholipid antibodies: Evaluation of the thrombotic risk
Abstract
The laboratory diagnosis of the antiphospholipid syndrome (APS) via antiphospholipid antibody (aPL) tests, including lupus anticoagulant (LAC), anti-cardiolipin (aCL), or anti-beta2 glycoprotein I (aβ2GPI) antibodies remains a challenge. Coagulation tests for LAC as well as solid phase assays for aCL and aβ2GPI have methodological shortcomings, although for LAC large progress have been made in standardization. All assays are associated with clinical APS-criteria (thrombotic and/or pregnancy complications) but with limited specificity. Besides, clinical studies demonstrating the association between the presence of aPL and thrombosis are not always well designed and result in wide ranges of odds ratio with large variation between studies. The best association between thrombotic complications and aPL is found for LAC. The association between thrombosis and aCL or aβ2GPI is at least inconsistent. The inclusion of more specific assays, such as the domain-I-β2GPI.antibodies is too premature and depends on further investigation in large clinical studies and the commercial availability. The search for new assays should proceed to identify patients with aPL with increased risk for thrombosis, preferable in large prospective studies. Meanwhile, with the current available LAC, aCL and aβ2GPI assays it is strongly recommended to make antibody profiles. Multiple positivity of tests seems clinically more relevant. The strengths and weaknesses of the current laboratory criteria for APS are discussed in view of their role in risk stratification of patients with thrombotic events.
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It is generally accepted that patients with isolated LAC have a lower risk profile in APS.
“It is generally accepted that patients with isolated LAC have alowerriskprofileinAPS 12,20”
From Clinical Relevance of Isolated Lupus Anticoagulant Positivity in Patients with Thrombotic Antiphospholipid Syndrome (2021) · cites this paper as [20]
Cites
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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
Galli, M., Luciani, D., Bertolini, G., & Barbui, T. (2003) · Blood · doi:10.1182/blood-2002-02-0441 · Cited by 974 · cited 8× · see citing works
“LAC is regarded as the strongest risk factor for thrombosis as demonstrated in many studies and often based on the review of Galli et al [25].”
BackgroundInfluentialClinical 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 · cited 3× · see citing works
“The agreement of isotype between aCL and aβ2GPI is believed to identify patients at higher risk [10,50].”
BackgroundPengo, V., Ruffatti, A., Legnani, C., Testa, S., Fierro, T., Marongiu, F., De Micheli, V., Gresele, P., Tonello, M., Ghirarduzzi, A., et al. (2011) · Blood · doi:10.1182/blood-2011-03-340232 · Cited by 465 · cited 1× · see citing works
“Triple positivity is frequent in APS patients at high risk for a new thromboembolic event, aswell as in carriers at risk developing a first event [66].”
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Runchey, S. S., Folsom, A. R., Tsai, M. Y., Cushman, M., & McGovern, P. D. (2002) · British Journal of Haematology · doi:10.1046/j.1365-2141.2002.03949.x · Cited by 72 · 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-citationLaboratory 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
Self-citationAntiphospholipid 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-citationChayoua, W., Kelchtermans, H., Moore, G. W., Musiał, J., Wahl, D., de Laat, B., & Devreese, K. M. J. (2018) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.14261 · Cited by 71 · see citing works
Self-citationYin, D., de Groot, P. G., Ninivaggi, M., Devreese, K. M. J., & de Laat, B. (2021) · Thrombosis and Haemostasis · doi:10.1055/a-1344-4271 · Cited by 36 · see citing works
Self-citationAntiphospholipid Antibodies and Recurrent Thrombotic Events: Persistence and Portfolio
Amory, C. F., Levine, S. R., Brey, R. L., Gebregziabher, M., Tuhrim, S., Tilley, B. C., Simpson, A.-C. C., Sacco, R. L., Mohr, J. P., & Collaborators, F. T. A.-W. (2015) · Cerebrovascular Diseases · doi:10.1159/000441362 · Cited by 31 · 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
- 2012-10
- Volume
- 130
- Pages
- S37-S40
- ISSN
- 0049-3848 (ISSN-L)
- OpenAlex
- W2084085262
- Cited by
- 56
- References
- 7
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 5 · 2020: 5 · 2019: 1 · 2018: 6 · 2017: 5 · 2016: 6 · 2015: 2 · 2014: 8 · 2013: 3
- FWCI
- 0.62
- 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 › Pulmonary and Respiratory Medicine › Vasculitis and related conditions
- Keywords
- antiphospholipid syndrome, antiphospholipid antibodies, lupus anticoagulant, anticardiolipin antibodies, anti-beta2-glycoprotein I antibodies, thrombosis risk, laboratory diagnosis, assay standardization, risk stratification, antibody profiles, pregnancy complications
- MeSH terms
- Animals, Blood Coagulation Tests, Humans, Immunologic Tests, Predictive Value of Tests, Prognosis, Risk Factors, Thrombosis, Biomarkers, Lupus Coagulation Inhibitor, Antiphospholipid Syndrome, Antibodies, Antiphospholipid, Antibodies, Anticardiolipin, Risk Assessment, Solid Phase Extraction, beta 2-Glycoprotein I
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