What is the recommended test for antiphospholipid (antiphospholipid) syndrome (APS)?

Recommended Tests for Antiphospholipid Syndrome (APS)

For diagnosing antiphospholipid syndrome, a comprehensive panel of three tests is required: lupus anticoagulant (LAC), anticardiolipin antibodies (aCL), and anti-β2-glycoprotein I antibodies (aβ2GPI) of IgG and IgM isotypes, with positive results confirmed on two occasions at least 12 weeks apart. 1, 2

Required Laboratory Testing

The International Society on Thrombosis and Haemostasis (ISTH) and American College of Rheumatology recommend the following tests:

1. Lupus Anticoagulant (LAC):

   • Must be detected using two phospholipid-dependent coagulation tests
   • Requires a 3-step methodology: screening, mixing, and confirmation
   • Parallel testing in APTT and dRVVT as first-choice clotting tests 1, 2

2. Anticardiolipin Antibodies (aCL):

   • Both IgG and IgM isotypes must be measured
   • Must be β2GPI-dependent to avoid detection of non-cofactor antibodies associated with infections
   • Measured by solid phase assays (ELISA or automated systems)
   • Positivity defined as >99th percentile of normal controls 1, 2

3. Anti-β2-glycoprotein I Antibodies (aβ2GPI):

   • Both IgG and IgM isotypes must be measured
   • Measured by solid phase assays (ELISA or automated systems)
   • Positivity defined as >99th percentile of normal controls 1, 2

Important Testing Considerations

• Persistence requirement: The same antibodies must be positive on two separate occasions at least 12 weeks apart for definitive diagnosis 1, 2

• Risk stratification: Comprehensive testing for all three antibodies is crucial as triple-positive patients have the highest risk for thrombosis and pregnancy morbidity 1, 2

• Timing of testing: Testing should ideally be done before anticoagulation is started, as anticoagulants can affect LAC testing results 2

• Interpretation: Laboratory results should be reviewed and interpreted through collaboration between a clinical pathologist and a clinician skilled at interpreting the data 1

Testing Methods

• Traditional ELISA methods are acceptable, but newer automated platforms using chemiluminescence, flow cytometry, or multiplex systems offer advantages:
  • More harmonized working conditions
  • Reduced inter-laboratory variation
  • Less labor intensive
  • Provide multiple results simultaneously 1, 3

Pitfalls and Caveats

1. LAC testing limitations:

   • No single test has sufficient sensitivity and specificity for LAC, necessitating multiple tests 1
   • Anticoagulant therapy can cause erroneous results 1, 4
   • Consider pretest anticoagulant removal procedures if patient is already on anticoagulants 2

2. aCL testing specificity:

   • Must be β2GPI-dependent to avoid false positives from infections or drugs 1
   • Specificity depends on the source and amount of β2GPI 1

3. Result interpretation:

   • Results should always be interpreted in relation to clinical symptoms 2
   • Isolated LAC positivity without ELISA test positivity carries a lower thrombosis risk 1

4. Other antibody tests:

   • Tests like anti-phosphatidylserine antibodies (aPS) may have diagnostic value but are not yet recommended for routine testing 1, 5

By following this comprehensive testing approach, clinicians can accurately diagnose APS and appropriately stratify patients' risk for thrombotic events and pregnancy complications.