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. In this study, a classification system based on both criteria and non‐criteria antiphospholipid antibodies (aPL) is proposed to identify patients with Obstetric Antiphospholipid Syndrome. The resulting group exhibits non‐criteria aPL, and aβ2GPI titers below the cut‐off but higher than those in healthy women. These patients retrospectively responded better to aspirin and/or heparin treatment.