What initial blood tests should be used to diagnose anti-phospholipid syndrome (APS)?

Initial Blood Tests for Antiphospholipid Syndrome Diagnosis

For initial diagnosis of antiphospholipid syndrome (APS), you should order a comprehensive panel consisting of lupus anticoagulant (LAC), anticardiolipin antibodies (aCL) IgG/IgM, and anti-β2 glycoprotein I antibodies (aβ2GPI) IgG/IgM tests concurrently. 1

Recommended Initial Laboratory Panel

1. Lupus Anticoagulant (LAC)

   • Must be measured in citrated plasma
   • Requires 3-step methodology: screening, mixing, and confirmation
   • Should include parallel testing in APTT and dRVVT as first-choice clotting tests 1
   • Testing requires two phospholipid-dependent coagulation tests for adequate sensitivity and specificity 1

2. Anticardiolipin Antibodies (aCL)

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

3. Anti-β2 Glycoprotein I Antibodies (aβ2GPI)

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

Important Testing Considerations

Timing and Confirmation

• For definitive diagnosis, the same antibodies must be positive on two separate occasions at least 12 weeks apart 1, 2
• This interval is crucial to rule out transient antibody positivity that can occur with infections or medications 1

Test Interpretation

• Results should be interpreted according to local cutoff values
• Low positive results around the cutoff value should be interpreted with caution (consider 10% imprecision of solid phase methods) 1
• Laboratory results should be reviewed collaboratively between a clinical pathologist and the treating clinician 1, 2

Antibody Profile Assessment

• Triple positivity (positive for all three tests) indicates highest risk for thrombosis and pregnancy morbidity 1, 2
• Double positivity (especially aCL and aβ2GPI with concordant isotype) also increases confidence in APS diagnosis 1
• IgG isotypes generally have greater clinical relevance than IgM isotypes 1

Testing Pitfalls to Avoid

• Anticoagulant Interference: LAC testing can be affected by anticoagulant treatments, especially vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) 1, 2

  • Ideally, assess LAC 1-2 weeks after discontinuation of VKA (if clinically feasible)
  • For patients on DOACs, consider pretest DOAC removal procedures 1

• Single Test Reliance: Using only one test for LAC increases risk of underdiagnosis by up to 31% 2

• Non-Recommended Initial Tests: Do not include antibodies against phosphatidylserine/prothrombin (aPS/PT) or domain I of β2GPI (aDI) in first-line testing 1

Clinical Context

The laboratory diagnosis must be interpreted in the context of clinical manifestations (vascular thrombosis and/or pregnancy morbidity) to establish APS diagnosis 2. The antibody profile helps determine thrombotic risk and guides management decisions, with triple-positive patients requiring more aggressive treatment approaches due to higher recurrence risk 3.

Remember that significant variability exists between laboratories and assays, emphasizing the need for standardized testing methods 2, 4. Always ensure your laboratory follows the International Society on Thrombosis and Haemostasis (ISTH) recommendations for these tests to minimize false results 1.