Repeat Testing for Negative APS Antibody Results
No, negative antiphospholipid antibody results do not require routine confirmation or repeat testing, unlike positive results which mandate confirmation at least 12 weeks apart. The laboratory criteria for APS diagnosis specifically require repeat testing only to confirm positive results and rule out transient positivity 1, 2, 3.
Rationale for the Recommendation
The ISTH-SSC guidelines explicitly state that repeat testing after 3 months was designed to avoid over-diagnosis by distinguishing persistent from transient positivity of antibodies 1. The 12-week confirmation requirement applies exclusively to positive test results to ensure reliability and persistence of antibody positivity before making an APS diagnosis 1, 2, 3.
When to Consider Retesting Negative Results
While routine repeat testing of negative results is not recommended, specific clinical scenarios warrant retesting:
High Clinical Suspicion Despite Negative Results
- If strong clinical suspicion persists (recurrent thrombosis, pregnancy morbidity) with negative standard aPL testing, consider retesting with alternative methods or at a later time point 1. Inter-assay and inter-laboratory variability means a sample testing negative in one assay may test positive in another 1.
Testing During Problematic Conditions
- Repeat testing should be performed if initial negative results were obtained during anticoagulation therapy, acute thrombosis, or pregnancy, as these conditions can produce false negative results 1.
Equivocal or Borderline Results
- Low positive or equivocal results near the cutoff value should be repeated to confirm true positivity or negativity 1. Assay imprecision (up to 10%) can affect classification around cutoff values 1.
Important Caveats
Seronegative APS Considerations
- A small subset of patients may have clinical manifestations consistent with APS but persistently negative standard aPL tests (so-called "seronegative APS") 4. In these cases, testing for non-criteria antibodies (aPS/PT, anti-domain I) may be considered in specialized centers 1, 3.
Antibody Fluctuation Over Time
- aPL can fluctuate or even become persistently negative in some patients (approximately 9% in long-term follow-up), most commonly in those with single antibody positivity 5, 6. However, this phenomenon applies to previously positive patients, not those with initial negative results.
Clinical Context is Paramount
- Test results must always be interpreted in clinical context with close laboratory-clinician interaction 1. A negative aPL panel in a patient without clinical features of APS requires no further testing.