From the Guidelines
The diagnostic criteria for Antiphospholipid Syndrome (APS) should be based on the presence of lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL), and anti-beta2 glycoprotein I antibodies (aβ2GPI), with aCL and aβ2GPI measurement restricted to enzyme-linked immunosorbent assays (ELISAs) with moderate and high titer aPL thresholds defined as 40 and 80 Units, respectively, as per the 2023 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) APS classification criteria 1.
When diagnosing APS, it is essential to differentiate between classification criteria and assessment of aPL in clinical care. Classification criteria are strict and meant for participant inclusion in studies and trials to study homogeneous populations of patients. In contrast, laboratory detection for APS diagnosis in daily practice is broader, meant to diagnose each APS patient to optimize their management. The following key points should be considered:
- Lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL), and anti-beta2 glycoprotein I antibodies (aβ2GPI) remain the cornerstone of the laboratory part of APS diagnosis 1.
- aCL and aβ2GPI measurement should be restricted to enzyme-linked immunosorbent assays (ELISAs) with moderate and high titer aPL thresholds defined as 40 and 80 Units, respectively 1.
- The role of other aPL, such as antiphosphatidylserine (aPS)/prothrombin (PT) antibodies, and the isotypes immunoglobulin (Ig)M and IgA, is still a matter of debate and requires further research 1.
- Patients diagnosed with the disease may or may not fulfill the classification criteria, and inappropriate use of classification criteria may lead to mis(under)diagnosis 1.
In clinical practice, the diagnosis of APS should be based on a combination of clinical and laboratory findings, including:
- Vascular thrombosis (arterial, venous, or small vessel) in any tissue or organ
- Pregnancy complications such as unexplained fetal death after 10 weeks, premature birth before 34 weeks due to preeclampsia or placental insufficiency, or three or more unexplained consecutive spontaneous abortions before 10 weeks
- Presence of lupus anticoagulant, anticardiolipin antibodies (IgG or IgM), or anti-β2 glycoprotein-I antibodies (IgG or IgM) at medium to high titers, as defined by the 2023 ACR/EULAR APS classification criteria 1.
From the Research
APLA Diagnostic Criteria
The diagnostic criteria for Antiphospholipid Syndrome (APS) require the presence of a clinical criterion (thrombosis and/or pregnancy morbidity), combined with persistently circulating antiphospholipid antibodies (aPL) 2. The laboratory criteria for aPL consist of:
- Lupus anticoagulant (LAC)
- Anticardiolipin antibodies (aCL) IgG/IgM
- Anti-β2 glycoprotein I antibodies (aβ2GPI) IgG/IgM
Laboratory Diagnosis
Laboratory diagnosis of APLA depends upon the detection of a lupus anticoagulant, which prolongs phospholipid-dependent anticoagulation tests, and/or anticardiolipin (aCL) and anti-β2-glycoprotein-1 (β2GPI) antibodies 3. LAC detection is based on functional coagulation assays, while aCL and aβ2GPI are measured with immunological solid-phase assays 2.
Challenges in Diagnosis
There are several challenges in the diagnosis of APS, including:
- Interference by anticoagulation therapy in LAC assays 2
- High variability between different solid-phase assays for aCL and aβ2GPI due to the lack of universal calibrators or standards 2
- Limited added value of non-criteria aPL, such as anti-domain I β2 glycoprotein I and antiphosphatidylserine/prothrombin antibodies, in the diagnosis of APS 2, 4
Interpretation of Results
The interpretation of aPL results is crucial in identifying patients at risk, and antibody profiles can help in this process 4. However, the technical aspects of laboratory methods and the clinical relevance of assays must be carefully considered to ensure accurate diagnosis and risk stratification of APS patients.