Diagnosis of Antiphospholipid Antibody Syndrome (APAS)
APAS diagnosis requires both a clinical criterion (thrombosis or pregnancy morbidity) AND persistent laboratory positivity for antiphospholipid antibodies, confirmed by repeat testing at least 12 weeks apart. 1
Mandatory Laboratory Testing
Three specific antibody tests must be performed in parallel for every suspected APAS case: 1, 2
1. Lupus Anticoagulant (LA)
- LA testing is mandatory and uses a 3-step methodology: screening, mixing, and confirmation 2, 3
- Both APTT-based AND dilute Russell's viper venom time (dRVVT) assays must be performed in parallel 2, 3
- Critical pitfall: Omitting either APTT or dRVVT leads to underdiagnosis in up to 55% of triple-positive patients 2, 3
- Results are reported as positive or negative 3
- Never perform LA testing during anticoagulation therapy—this causes false positives or false negatives 3, 4
2. Anticardiolipin Antibodies (aCL)
- Test both IgG and IgM isotypes using solid-phase assays (ELISA or validated automated systems) 1, 2
- Positivity defined as values above the 99th percentile of normal controls 1, 2
- The 2023 ACR/EULAR criteria define moderate titer as >40 Units and high titer as >80 Units 1, 2
- Results must be reported with their quantitative level 2, 4
3. Anti-β2 Glycoprotein I Antibodies (aβ2GPI)
- Test both IgG and IgM isotypes using solid-phase assays (ELISA or validated automated systems) 1, 2
- Same positivity thresholds as aCL: above 99th percentile, with moderate (>40 U) and high (>80 U) titer thresholds 1, 2
- Results must be reported with their quantitative level 2, 4
Confirmation Requirement
All positive results must be confirmed by repeat testing at least 12 weeks (but not more than 5 years) after the initial test to establish persistence and rule out transient antibody presence. 1, 4, 5
Risk Stratification Based on Laboratory Profile
The antibody profile determines thrombotic risk and guides management intensity: 2, 4
- Triple positivity (LA + aCL + aβ2GPI all positive): Highest risk 2, 3, 4
- Double positivity with concordant isotype (both aCL and aβ2GPI of same isotype, especially IgG): High risk 2, 3
- Medium/high titer antibodies (>40 Units): Higher risk than low-positive 2, 4
- IgG isotype: More clinically relevant than IgM 2, 3, 4
- Single LA positivity alone: Lower risk compared to triple positivity 1, 3
Clinical Criteria Required for Diagnosis
At least one of the following clinical manifestations must be present: 1, 6
Vascular Thrombosis
- One or more episodes of arterial, venous, or small vessel thrombosis in any tissue or organ 6, 7
- Must be confirmed by objective validated criteria (imaging or histopathology) 6
Pregnancy Morbidity
- Three or more consecutive spontaneous losses before 10 weeks' gestation 2
- One or more unexplained fetal deaths at or after 10 weeks' gestation 2
- One or more premature births before 34 weeks due to preeclampsia, eclampsia, placental insufficiency, or intrauterine growth restriction 2
Critical Pitfalls to Avoid
- Never test for LA during anticoagulation therapy—this is the most common source of false results 3, 4
- Never rely on a single positive test—confirmation at 12 weeks is mandatory 1, 4
- Never use only one LA assay (APTT or dRVVT alone)—both are required 2, 3
- Low-positive results near threshold values should be interpreted cautiously due to 10% assay imprecision 3
- Classification criteria are stricter than clinical diagnostic criteria—inappropriate use of classification criteria may lead to underdiagnosis 1, 3
Ongoing Monitoring
Annual retesting of LA, aCL, and aβ2GPI is recommended to evaluate titer fluctuation and changes in antibody profile over time. 2, 3, 4