Anti-phospholipid Antibodies (aPL) as Prognostic Markers

Anti-phospholipid antibody (aPL) testing is used in the evaluation of suspected antiphospholipid syndrome (APS). aPL may also be detected in patients with systemic lupus erythematosus (SLE) and can inform the assessment of APS-related thrombotic or obstetric risk when interpreted together with established clinical criteria.

A recent 10-year cohort study published in The American Journal of Medicine (2026) investigated the prognostic significance of aPL positivity in hospitalized patients without APS or SLE. The study reported an association between aPL positivity and long-term mortality and hospital readmission under the study conditions.

The study was conducted at Sheba Medical Center (Israel) and included nearly 5,000 hospitalized patients without APS or SLE¹. The investigators evaluated the association between aPL positivity and long-term clinical outcomes using classical aPL ELISAs recommended by the APS classification criteria.

📌 Key Findings

Anti-cardiolipin IgG and Lupus anticoagulant (LA) showed the strongest associations with mortality, independent of APS or SLE diagnosis, thrombotic history, or other comorbidities.
Low-titer IgM aPL (anti-β2GPI, anti-cardiolipin) were also linked to increased mortality, challenging traditional classification criteria that often underweight IgM antibodies²³.
Thrombotic events did not explain the risk, suggesting non-thrombotic mechanisms (e.g., endothelial dysfunction, inflammation).

Patients (no APS or SLE)	aPL-Positive (n=1,485)	aPL-Negative (n=3,316)	Hazard Ratio (HR)
10-Year Mortality	21.8%	12%	1.40
1-Year Readmission	40.9%	32.8%	1.25

🏥 Clinical Implications and conclusion

This study highlights the prognostic significance of anti-phospholipid antibodies (aPL) positivity in hospitalized patients, independent of traditional risk factors. The findings underscore the importance of including aPL testing in risk stratification frameworks to identify high-risk individuals early.

The prognostic value of anti-cardiolipin IgG, which can act in a cofactor-independent manner⁴, further emphasizes the need for comprehensive aPL testing beyond β2GPI-dependent antibodies. Recent studies also demonstrate that some aPLs bind directly to cell-surface targets such as the EPCR/LBPA complex—where LBPA is a phospholipid structurally similar to phosphatidylglycerol and cardiolipin—and that statins may inhibit this binding⁵. This supports the pathogenic role of cofactor-independent aPLs and highlights the importance of detecting all relevant aPL subtypes.

Read more on the value of aPL in severe pregnancy complications due to obstetric anti-phospholipid syndrome, here 👈.

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