What are the clinical criteria for diagnosing antiphospholipid syndrome (APS)?

Clinical Criteria for Diagnosing Antiphospholipid Syndrome

The diagnosis of APS requires BOTH a clinical criterion (thrombosis or pregnancy morbidity) AND laboratory confirmation of antiphospholipid antibodies, with positive tests confirmed at least 12 weeks apart. 1, 2

Clinical Criteria

You must document at least ONE of the following clinical manifestations:

Vascular Thrombosis

• Any vascular bed can be affected—venous, arterial, or small vessel thrombosis 3
• This includes deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, or microvascular occlusions 3
• The thrombotic event must be confirmed by objective validated criteria (imaging studies, histopathology) 4

Pregnancy Morbidity

• One or more unexplained deaths of a morphologically normal fetus at or beyond 10 weeks of gestation 2
• One or more premature births of a morphologically normal neonate before 34 weeks due to eclampsia, severe preeclampsia, or placental insufficiency 2
• Three or more unexplained consecutive spontaneous abortions before 10 weeks of gestation (after excluding anatomic, hormonal, and chromosomal causes) 2

Laboratory Criteria

You must confirm at least ONE of the following antibodies on two separate occasions at least 12 weeks apart: 1, 2

The Three Required Tests

• Lupus anticoagulant (LAC) detected by functional phospholipid-dependent clotting assays 1
• Anticardiolipin antibodies (aCL) IgG or IgM isotype at levels >99th percentile (or per 2023 ACR/EULAR criteria: moderate titer ≥40 Units or high titer ≥80 Units) 1
• Anti-β2-glycoprotein I antibodies (aβ2GPI) IgG or IgM isotype at levels >99th percentile (or moderate/high titers as above) 1

Critical Testing Requirements

• All three tests should be performed simultaneously on the same sample to fully characterize the antibody profile 1
• The 12-week confirmation interval is mandatory to exclude transient antibody positivity from infections or other causes 1, 2
• Only IgG and IgM isotypes are included in classification criteria; IgA remains controversial 1

Risk Stratification Based on Antibody Profile

Triple-positive patients (LAC + aCL + aβ2GPI of same isotype) have the highest risk of thrombosis and pregnancy complications and should be managed most aggressively 1, 2

• Triple positivity shows the strongest association with both thrombotic and obstetric APS 1, 2
• Single antibody positivity confers lower risk 5
• β2GPI domain I antibodies (aD1), while not part of diagnostic criteria, confirm higher thrombotic risk when present in triple-positive patients 1

Common Pitfalls to Avoid

• Do not diagnose APS based on a single positive test—the 12-week confirmation is essential to avoid over-diagnosis 1, 2
• Do not test during acute thrombosis or anticoagulation when possible, as these interfere with LAC assays 4
• Do not ignore the clinical context—antibodies without clinical manifestations do not constitute APS; these patients are asymptomatic carriers 5
• Be aware of significant inter-laboratory variability in solid-phase assays for aCL and aβ2GPI due to lack of universal calibrators 4
• Consider APS in any patient with unexplained thrombosis (especially in unusual sites) or recurrent pregnancy loss, as it remains frequently overlooked across medical specialties 3