Evans Syndrome Predicts Progression to Antiphospholipid Syndrome and/or Systemic Lupus Erythematosus in Children with Persistent Antiphospholipid Antibodies: A Prospective Cohort Study with Up to 29 Years of Follow‐up

OBJECTIVE: To characterize the long-term clinical course of children with hematologic non-criteria manifestations and persistent antiphospholipid antibodies (aPL), and to identify predictors of progression to antiphospholipid syndrome (APS) and/or systemic lupus erythematosus (SLE). METHODS: We conducted a prospective cohort study of children (<18 years) with persistent aPL positivity and hematologic involvement (thrombocytopenia, autoimmune hemolytic anemia [AIHA], or Evans syndrome) followed at a tertiary pediatric rheumatology center between 1995 and 2024, with follow-up extending into adulthood. Progression to clinically classifiable APS and/or SLE was the primary endpoint. Kaplan-Meier and Cox proportional hazards models evaluated predictors at presentation and in complementary time-dependent analyses. RESULTS: Among 42 enrolled children, 40 were evaluable, of whom 11 (27.5%) progressed to APS and/or SLE. Evans syndrome at presentation was associated with the highest hazard of progression compared with isolated thrombocytopenia (HR 6.21, 95% CI 1.46-26.41). In time-dependent analyses, Evans syndrome emerging during follow-up remained associated with progression. Isolated thrombocytopenia showed the lowest risk, whereas AIHA represented an intermediate state that did not independently predict progression. Lupus anticoagulant was nearly universal, and broader high-risk aPL profiles were more common among progressors but were not statistically significant. CONCLUSION: In children with persistent aPL positivity, Evans syndrome was the hematologic phenotype most strongly associated with progression to APS and/or SLE, whereas isolated thrombocytopenia followed a largely indolent course. Evolving hematologic phenotypes may improve risk stratification and inform long-term monitoring strategies within the APS-SLE spectrum.