Antiphospholipid Antibody Panel: Expected Components and Values
Standard Panel Components (Blue Top Tube - Sodium Citrate)
The antiphospholipid antibody panel consists of three mandatory tests: lupus anticoagulant (LAC), anticardiolipin antibodies (aCL) IgG and IgM, and anti-β2-glycoprotein I antibodies (aβ2GPI) IgG and IgM, all performed on the same citrated plasma sample. 1
1. Lupus Anticoagulant (LAC)
- Detected using phospholipid-dependent clotting assays (typically dilute Russell's viper venom time [dRVVT] and/or activated partial thromboplastin time [aPTT]) 1
- Result reported as positive or negative based on mixing studies and confirmatory testing with excess phospholipid 2
- LAC is the strongest predictor for thrombotic events and adverse pregnancy outcomes, independent of other aPL 3
2. Anticardiolipin Antibodies (aCL)
- IgG and IgM isotypes measured by ELISA or automated solid-phase assays 1
- Positive threshold: >99th percentile of normal controls 1
- The 2023 ACR/EULAR criteria use moderate (40 Units) and high (80 Units) titer thresholds instead of the 99th percentile 1
- Must be β2GPI-dependent to be clinically significant 1
3. Anti-β2-Glycoprotein I Antibodies (aβ2GPI)
- IgG and IgM isotypes measured by ELISA or automated solid-phase assays 1
- Positive threshold: >99th percentile of normal controls 1
- The 2023 ACR/EULAR criteria use moderate (40 Units) and high (80 Units) titer thresholds 1
Risk Stratification Based on Antibody Profile
Triple Positivity (Highest Risk)
- LAC + aCL + aβ2GPI (same isotype) indicates the strongest association with thrombotic and obstetric APS 3, 1
- Triple-positive patients have the highest risk of recurrent thrombosis or development of first thrombosis 3
Double Positivity (Intermediate Risk)
- Two positive tests (typically LAC negative) indicate generally lower risk than triple positivity 3
- In these patients, aβ2GPI levels may be insufficient to induce LAC positivity 3
Single Positivity (Lower Risk)
- Single-positive patients (LAC alone, aCL alone, or aβ2GPI alone) are less likely to develop aPL-related events 3
- However, LAC positivity alone remains the main predictor for thrombotic events in obstetric APS and arterial thrombosis 3
Critical Testing Requirements
Confirmation Testing
- All positive results must be confirmed with repeat testing at least 12 weeks (3 months) apart 3, 1
- This requirement distinguishes persistent from transient antibody positivity and ensures test reliability 3
Timing Considerations
- Avoid testing during anticoagulation therapy (VKA, DOAC, heparin), acute thrombosis, or pregnancy, as these produce false negative or unreliable results 1
- Factor VIII increases during pregnancy can mask lupus anticoagulant by shortening aPTT 1
- Antibody levels may decrease during acute thrombosis due to antibody deposition at the thrombotic site 1
Common Pitfalls
Inter-Laboratory Variability
- A sample testing positive in one assay does not automatically test positive in assays from different manufacturers or laboratories 3
- Test results should always be related to clinical symptoms with close laboratory-clinician interaction 3, 1
IgA Antibodies
- IgA aCL and aβ2GPI are NOT included in classification criteria, and their significance remains controversial 1
Low Positive or Equivocal Results
- Results near the cutoff value should be repeated to confirm true positivity or negativity, as assay imprecision (up to 10%) can affect classification 1
Emerging Biomarkers (Not Standard Panel)
β2GPI Domain I Antibodies (aD1)
- Strongly associated with thrombosis and mainly present in triple-positive patients 3, 1
- Currently considered confirmation of higher thrombotic risk rather than replacement for standard aβ2GPI testing 3, 1