Patterns and clinical relevance of antiphospholipid antibody profiles in children

The clinical significance of antiphospholipid antibody (aPL) profiles and persistence patterns in children is not well defined. This study aimed to characterize patterns of aPL positivity in children, and describe thrombotic and non-thrombotic manifestations, stratified by aPL profiles. In this single-center retrospective cohort study, we identified patients aged ≤ 18 years with at least one confirmed positive aPL result between 2003 and 2024. Persistent aPL positivity was defined as repeat positivity ≥ 12 weeks apart; transient positivity was defined as an initial positive result followed by a negative result on repeat testing. Antiphospholipid antibody profiles were classified as high-risk (lupus anticoagulant test [LA] positive, and/or anticardiolipin antibody [aCL] or anti–β 2 -glycoprotein-I antibody [aβ 2 GPI] IgG/IgM ≥ 40 U) or low-risk (LA negative with aCL and/or aβ 2 GPI IgG/IgM 20–39 U). Clinical features were compared using chi-square or Fisher’s exact test, as appropriate. Among 462 patients with documented initial aPL positivity, 246 (53%) had no repeat testing, 128 (28%) had transient aPL positivity, and 88 (19%) had persistent aPL positivity. Persistent aPL positivity varied by the antibody profile, occurring in 42% of initially LA-positive patients, while persistence of aCL and aβ 2 GPI increased with antibody level, reaching 75–78% when levels exceeded 80 U. Compared with patients with transient aPL positivity, those with persistent aPL positivity (72/88 [82%] with high-risk profiles) had higher rates of systemic lupus erythematosus (35% vs. 19%), venous or arterial thrombosis (48% vs. 22%), thrombocytopenia (30% vs. 7%), autoimmune hemolytic anemia (AIHA) (9% vs. 1%), and selected neurologic manifestations. Within the persistently aPL-positive cohort, arterial thrombosis (22% vs. 0%) and recurrent thrombosis (19% vs. 0%) were observed only in patients with high-risk aPL profiles. Persistent aPL positivity was documented in one-fifth of patients with at least one positive aPL test, while transient positivity or lack of repeat testing were common. Patients with persistent aPL positivity had a greater burden of thrombotic and non-thrombotic manifestations than those with transient positivity. The exclusive occurrence of arterial and recurrent thrombosis among persistently aPL-positive patients with high-risk aPL profiles supports the utility of serologic risk stratification. These findings highlight the importance of confirming persistence and incorporating risk stratification when interpreting aPL positivity in children.