Improving diagnosis in patients with obstetric antiphospholipid syndrome through the evaluation of non-criteria antibodies

Objectives: Antiphospholipid syndrome (APS) is an autoimmune disease driven by antiphospholipid antibodies (aPL). Currently, APS diagnosis requires a combination of clinical manifestations (thrombosis and/or obstetric morbidity) and the persistent presence of at least one criteria aPL: anti-cardiolipin antibodies (aCL), anti-β2-glycoprotein I antibodies (aβ2GPI) or lupus anticoagulant (LA). Patients with suggestive obstetric symptoms but lacking criteria aPL face diagnostic challenges. Non-criteria aPL screening may enhance discrimination. This study proposes a classification incorporating both criteria and non-criteria antibodies to improve obstetric APS diagnosis.

Methods: Blood samples from non-pregnant women (n = 68) with a history of vascular, obstetric, or vascular and obstetric manifestations were analysed. Among them, 30 had previous diagnosis of APS. Healthy women with proven gestational success were included as controls (n = 16). Criteria and non-criteria (anti-phosphatidylglycerol, anti-phosphatidylethanolamine, anti-phosphatidylinositol, anti-phosphatidylserine and anti-phosphatidic acid) IgG aPL were evaluated by ELISA and coagulation tests. Based on the resulting aPL profile, patients were reclassified. Responsiveness to treatment was obtained from medical records.

Results: Criteria aPL levels marginally differentiated women previously managed as obstetric APS from unexplained/other causes of obstetric morbidity. Including non-criteria aPL improved separation. The proposed classification identified an obstetric APS group that exhibits non-criteria aPL and aβ2GPI titres below the cut-off but higher than healthy women (7.88 vs. 2.47 SGU, P = 0.006). Compared to cases of other causes of obstetric morbidity, these patients retrospectively responded better to aspirin and/or heparin treatment (71.43% vs. 11.11%, P = 0.035).

Conclusions: Assessing non-criteria antibodies may identify isolated obstetric APS cases benefiting from established therapies.