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Cited by 76Systemic Lupus Erythematosus ResearchBlood Coagulation and Thrombosis MechanismsVasculitis and related conditions

Laboratory Diagnosis of Antiphospholipid Syndrome: Insights and Hindrances

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Vandevelde, Arne, Devreese, Katrien M. J.·2022·Journal of Clinical Medicine
DOI 10.3390/jcm11082164PMC PMC9025581
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Abstract

Diagnosis of antiphospholipid syndrome (APS) requires the presence of a clinical criterion (thrombosis and/or pregnancy morbidity), combined with persistently circulating antiphospholipid antibodies (aPL). Currently, laboratory criteria aPL consist of lupus anticoagulant (LAC), anticardiolipin antibodies (aCL) IgG/IgM, and anti-β2 glycoprotein I antibodies (aβ2GPI) IgG/IgM. Diagnosis and risk stratification of APS are complex and efforts to standardize and optimize laboratory tests have been ongoing since the initial description of the syndrome. LAC detection is based on functional coagulation assays, while aCL and aβ2GPI are measured with immunological solid-phase assays. LAC assays are especially prone to interference by anticoagulation therapy, but strategies to circumvent this interference are promising. Alternative techniques such as thrombin generation for LAC detection and to estimate LAC pathogenicity have been suggested, but are not applicable yet in routine setting. For aCL and aβ2GPI, a lot of different assays and detection techniques such as enzyme-linked immunosorbent and chemiluminescent assays are available. Furthermore, a lack of universal calibrators or standards results in high variability between the different solid-phase assays. Other non-criteria aPL such as anti-domain I β2 glycoprotein I and antiphosphatidylserine/prothrombin antibodies have been suggested for risk stratification purposes in APS, while their added value to diagnostic criteria seems limited. In this review, we will describe laboratory assays for diagnostic and risk evaluation in APS, integrating applicable guidelines and classification criteria. Current insights and hindrances are addressed with respect to both laboratory and clinical implications.

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  • For the search for aCL and aβ2-GP-I, several different assays and detection techniques are currently available, making these tests relatively reliable and widespread.

    “For the search for aCL and aβ2-GP-I, traditionally performed by solid-phase immunoassays (ELISA), several different assays and detection techniques are currently available, thus making these tests relatively reliable and widespread [7].”

    From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [7]

    Section 4.1 confirms that aCL and aβ2GPI testing traditionally uses ELISA and that several alternative techniques and commercial assays are available. It does not support the inference that this variety makes the tests relatively reliable: the same section reports high inter-assay variability and poor agreement between assays. It says automated testing is increasingly used in laboratories, but not universally available. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • dRVVT is not influenced by factor VIII levels, as factor X is directly activated by the diluted Russell's viper venom.

    “while dRVVT is not influenced by factor VIII levels, as factor X is directly activated by the diluted Russell’s viper venom [7].”

    From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [7]

  • The first approach (ISTH in-house cut-offs) is characterized by increased specificity and a statistically inevitable reduction of sensitivity, partially counterbalanced by the use of two assays.

    “The first approach is characterized by an increased specificity (that reduces false positives) and a statistically inevitable reduction of sensitivity (partially counterbalanced by the use of two assays) [7].”

    From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [7]

  • VKA cause an acquired deficiency of factors II, VII, IX, and X that can give false positives in screening tests and false negatives in mixing tests.

    “These drugs cause an acquired deficiency of factors II, VII, IX, and X that can give false positives in screening tests and false negatives in mixing tests [7].”

    From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [7]

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Authors
Vandevelde, A., & Devreese, K. M. J.
Affiliations
Ghent University Hospital (BE)
Corresponding author
Devreese, Katrien M. J.
ORCID
Venue
Journal of Clinical Medicine
Publisher
MDPI AG
Published
2022-04-13
Volume
11
Issue
8
Pages
2164
ISSN
2077-0383 (ISSN-L)
DOI
10.3390/jcm11082164
PMC
PMC9025581
OpenAlex
W4223978464
Cited by
76
References
208
Citations by year
2026: 14 · 2025: 20 · 2024: 27 · 2023: 13 · 2022: 2
FWCI
2.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Clinical Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
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, thrombin generation, risk stratification, classification criteria, anti-phosphatidylserine/prothrombin antibodies

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