What are the diagnostic criteria for Antiphospholipid Syndrome (APS)?

Diagnostic Criteria for Antiphospholipid Syndrome (APS)

The diagnosis of Antiphospholipid Syndrome (APS) requires the presence of at least one clinical criterion (vascular thrombosis or pregnancy morbidity) AND at least one laboratory criterion (persistent presence of antiphospholipid antibodies) confirmed on two separate occasions at least 12 weeks apart. 1

Clinical Criteria

1. Vascular Thrombosis

• One or more episodes of arterial, venous, or small vessel thrombosis in any tissue or organ
• Must be confirmed by objective validated criteria (imaging studies or histopathology)
• For histopathological confirmation, thrombosis should be present without significant inflammation in the vessel wall 1

2. Pregnancy Morbidity

Any one of the following:

• One or more unexplained deaths of morphologically normal fetuses at or beyond the 10th week of gestation
• One or more premature births of morphologically normal neonates before the 34th week of gestation due to:
  • Severe preeclampsia
  • Eclampsia
  • Placental insufficiency
• Three or more unexplained consecutive spontaneous abortions before the 10th week of gestation, with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded 1

Laboratory Criteria

Presence of any one of the following antiphospholipid antibodies on two or more occasions at least 12 weeks apart:

1. Lupus Anticoagulant (LA)

• Detected according to the guidelines of the International Society on Thrombosis and Haemostasis (ISTH)
• Requires two phospholipid-dependent coagulation tests, including dRVVT and APTT 1, 2

2. Anticardiolipin Antibodies (aCL)

• IgG and/or IgM isotype in medium or high titer (>99th percentile)
• Measured by standardized ELISA or other solid-phase assays 1, 3

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

• IgG and/or IgM isotype in high titer (>99th percentile)
• Measured by standardized ELISA or other solid-phase assays 1, 3

Important Considerations

Testing Recommendations

• Testing should ideally be performed before starting anticoagulation therapy 1
• The same antibody must be positive on two separate occasions at least 12 weeks apart to confirm persistence 1, 2
• Triple positivity (positive for all three antibody types) carries the highest risk for thrombosis and pregnancy morbidity 1

Common Pitfalls

1. Transient antibody positivity: A single positive test is insufficient for diagnosis; persistence must be confirmed after at least 12 weeks 1, 4
2. Interference with LA testing: Anticoagulant therapy can interfere with LA detection, potentially leading to false results 3
3. Variability in solid-phase assays: Lack of universal calibrators results in high variability between different aCL and aβ2GPI assays 3
4. Interpretation in clinical context: Results should always be interpreted in relation to clinical symptoms 1

Non-criteria Antibodies

• Antiphosphatidylserine antibodies (aPS) may have diagnostic value, especially in cases where other aPL tests are negative 5
• Anti-domain I β2 glycoprotein I and antiphosphatidylserine/prothrombin antibodies have been suggested for risk stratification but are not currently included in the diagnostic criteria 3

Risk Stratification

• Triple positivity (positive for all three antibody types) indicates the highest risk profile 1
• The type and titer of antibodies present can help determine the risk of thrombosis and pregnancy complications 1, 6
• Additional risk factors (traditional cardiovascular risk factors, autoimmune disorders) should be considered in the overall risk assessment 1