From the Guidelines
Diagnosing Anti-Phospholipid Syndrome (APS) involves detecting and interpreting antiphospholipid antibodies (aPL) through laboratory criteria, including persistent lupus anticoagulant (LA), anticardiolipin (aCL), and anti-β2GPI (aβ2GPI) antibodies.
Key Laboratory Criteria
- The 2023 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria for APS emphasize the importance of persistent LA, aCL, and aβ2GPI antibodies in diagnosing APS 1.
- Measurement of aCL and aβ2GPI is restricted to ELISA, with moderate and high titer thresholds set at 40 Unit (U) and 80 U levels, respectively 1.
- The detection and interpretation of aPL for classification purposes differ from those used in routine clinical care, with classification criteria aiming to enhance specificity and improve research quality 1.
Diagnostic Considerations
- Inter-assay and inter-laboratory variability, as well as the performance characteristics of assays, should be considered when making antibody profiles 1.
- Testing with other methods can be useful in patients with high clinical suspicion, and test results should always be related to clinical symptoms 1.
- An interaction between the laboratory and clinician is essential for accurate interpretation of aPL results 1.
From the Research
Diagnosis of Anti-Phospholipid Syndrome (APS)
The diagnosis of APS requires the presence of a clinical criterion (thrombosis and/or pregnancy morbidity), combined with persistently circulating antiphospholipid antibodies (aPL) 2, 3, 4, 5, 6. The laboratory criteria for APS consist of:
- Lupus anticoagulant (LAC)
- Anticardiolipin antibodies (aCL) IgG/IgM
- Anti-β2 glycoprotein I antibodies (aβ2GPI) IgG/IgM
Laboratory Tests for APS
The tests recommended for detecting aPL are:
- Standardized enzyme-linked immunosorbent assay (ELISA) to detect aCL and aβ2GPI 4, 5
- Clotting assays for LAC performed according to the guidelines of the International Society on Thrombosis and Haemostasis 4
- Semi-quantitative solid-phase assays to identify aCL and anti-β2GPI 5
- Phospholipid-dependent coagulation assays to detect LA 5
Challenges in Diagnosing APS
The diagnosis of APS is complicated by:
- Significant heterogeneity in patients' clinical presentation, underlying vascular risk factors, and methods of detecting antiphospholipid antibodies 3
- Interassay differences in solid-phase assays for aCL and aβ2GPI 6
- Interference of anticoagulant therapy with LAC measurement 2, 6
- Lack of universal calibrators or standards, resulting in high variability between different solid-phase assays 2