What is APLA Positive?
APLA (antiphospholipid antibody) positivity refers to the laboratory detection of autoantibodies directed against phospholipid-binding proteins in the blood, which must be confirmed on repeat testing at least 12 weeks apart to distinguish persistent from transient antibodies. 1, 2
Core Laboratory Tests
APLA positivity is defined by the presence of one or more of three specific antibodies 2, 3:
- Lupus anticoagulant (LA): A functional plasma test using phospholipid-dependent clotting assays (requires two different assays for detection) 2, 4
- Anticardiolipin antibodies (aCL): IgG and/or IgM isotypes measured by ELISA, present at levels >99th percentile of normal controls 2
- Anti-β2-glycoprotein I antibodies (aβ2GPI): IgG and/or IgM isotypes measured by ELISA, present at levels >99th percentile 2
Confirmation Requirements
All positive tests must be confirmed by repeat testing after at least 12 weeks to avoid over-diagnosis from transient antibody positivity. 1, 2, 3 This confirmation requirement applies exclusively to positive results, not negative ones. 2 Transient antibodies commonly occur with infections and certain medications. 1, 3
Risk Stratification by Antibody Profile
The clinical significance varies dramatically based on which antibodies are positive 1, 3:
- Triple-positive profile (LA + aCL + aβ2GPI of same isotype): Highest thrombotic risk and strongest association with clinical events 1, 5, 3
- Double-positive profile: Intermediate risk 3
- Single-positive profile: Lower risk, particularly isolated IgM positivity 1
- Isolated LA positivity: Carries significant thrombotic risk even as a single positive test 1
Among the three antibodies, LA conveys the greatest risk for adverse outcomes, with a relative risk of 12.15 for adverse pregnancy outcomes. 1
Isotype Considerations
IgG antibodies show stronger association with clinical events than IgM antibodies. 1 However, the role of IgM differs between thrombotic and obstetric presentations 1:
- In thrombotic APS: IgM testing is not strictly necessary first-line but useful for risk stratification 1
- In obstetric APS: Both IgG and IgM should be tested, as isolated IgM is more frequent and represents an independent risk factor 1
- IgA antibodies: Insufficient evidence for routine diagnostic testing, though associations exist particularly in systemic lupus erythematosus 1
Clinical Context
APLA positivity does not automatically equal disease 6, 4. These antibodies occur in 6, 7:
- Healthy individuals (particularly elderly)
- Patients with infections
- Patients with cancer (6% prevalence in some populations)
- Pregnant women without APS (6% prevalence)
- Other autoimmune diseases (SLE, systemic sclerosis, Sjögren's syndrome)
The diagnosis of antiphospholipid syndrome (APS) requires both persistent laboratory positivity AND clinical manifestations (thrombosis or pregnancy morbidity). 2, 4
Testing Pitfalls
Several factors can produce unreliable results 1, 2:
- Anticoagulation therapy: Warfarin, DOACs, and heparin interfere with LA testing 1, 2
- Pregnancy: Factor VIII increases can mask LA by shortening APTT 1, 2
- Acute thrombosis: Antibody levels may decrease due to deposition at thrombotic sites 1
- Assay variability: Results near cutoff values (within 10%) should be interpreted cautiously and repeated 1, 2
Emerging Biomarkers
Anti-phosphatidylserine/prothrombin antibodies (aPS/PT) show strong association with thrombosis (85% prevalence in LA-positive patients) but are not yet part of standard diagnostic criteria. 1 They may be useful when LA testing is unreliable or uncertain. 1