What is the best investigation for recurrent pregnancy losses in patients suspected to have Antiphospholipid Syndrome (APS)?

Best Investigation for Recurrent Pregnancy Losses in Suspected Antiphospholipid Syndrome (APS)

For patients with recurrent pregnancy losses suspected of having Antiphospholipid Syndrome (APS), lupus anticoagulant (LA) testing is the most important investigation, followed by anticardiolipin antibodies (aCL) and anti-β2 glycoprotein I antibodies (aβ2GPI). Among the options presented, ANA (antinuclear antibody) would be more appropriate than B2 microglobulin.

Recommended Laboratory Testing for APS

The diagnosis of APS requires specific laboratory criteria along with clinical manifestations. According to the International Society on Thrombosis and Haemostasis (ISTH) and American College of Rheumatology (ACR) guidelines, the following tests are essential:

1. Lupus Anticoagulant (LA) - detected according to standardized protocols 1

   • Requires multiple tests including dRVVT (dilute Russell's viper venom time) and APTT (activated partial thromboplastin time)
   • Strongest association with pregnancy morbidity

2. Anticardiolipin antibodies (aCL) - IgG/IgM isotypes 1

   • Must be β2GPI-dependent
   • Measured at levels > 99th percentile or >40 units

3. Anti-β2 glycoprotein I antibodies (aβ2GPI) - IgG/IgM isotypes 1

   • Measured at levels > 99th percentile or >40 units

Why These Tests Are Superior to Other Options

• Lupus anticoagulant (LA) has been confirmed as the strongest risk factor for pregnancy morbidity 1
• In obstetric APS, LA positivity is the main predictor for adverse pregnancy outcomes 1
• Tests must be positive on two occasions at least 12 weeks apart to confirm diagnosis 1

Antibody Profiles and Risk Assessment

The risk of pregnancy complications varies according to antibody profile:

• Triple positivity (LA + aCL + aβ2GPI) carries the highest risk 1
• Double positivity (any two tests positive) carries intermediate risk
• Single positivity (only one test positive) carries lower risk

Why ANA Is Preferred Over B2 Microglobulin

• ANA testing is valuable because APS can be secondary to Systemic Lupus Erythematosus (SLE) 2
• B2 microglobulin is not included in any guideline for APS diagnosis
• B2 microglobulin is not specific for APS and is more relevant to other conditions like renal dysfunction or lymphoproliferative disorders

Clinical Pitfalls to Avoid

1. Timing of testing - Antibody levels may fluctuate during pregnancy or after thrombotic events; ideally test before pregnancy or at least 12 weeks after delivery/thrombotic event 1

2. Single testing is insufficient - Persistent positivity (two positive tests at least 12 weeks apart) is required for diagnosis 1

3. Incomplete antibody profile - Testing only one antibody increases the risk of underdiagnosis; comprehensive testing (LA, aCL, and aβ2GPI) is essential 1

4. Interpretation errors - Laboratory results should be reviewed collaboratively between a clinical pathologist and clinician skilled in data interpretation 1

5. Anticoagulant therapy interference - LA testing during anticoagulant therapy may yield false results 1

Conclusion

When investigating recurrent pregnancy losses with suspected APS, a complete antiphospholipid antibody panel (LA, aCL, and aβ2GPI) should be ordered. Between the options presented in the question, ANA would be more appropriate than B2 microglobulin, particularly to identify potential secondary APS associated with SLE.