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.

Abstract

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). 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. 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. 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.