Silvia Grazietta Foddai, Irene Cecchi, Massimo Radin, Laura Bertolaccini, Danieli de Andrade, Maria Tektonidou, Vittorio Pengo, Chary Lopez-Pedrera, Diana Paredes-Ruiz, Howard Michael Belmont, Paul R Fortin, Denis Wahl, Ware Branch, Maria Gerosa, Guilherme de Jesus, Zhouli Zhang, Tatsuya Atsumi, Maria Efthymiou, Laura Andreoli, Esther Rodriguez, Michelle Petri, Ricard Cervera, Bahar Artim-Esen, Rosana Quintana, Jason S Knight, Rohan Willis, Reyhan Kose Cobanoglu, Hannah Cohen, Doruk Erkan, Savino Sciascia
ObjectiveWhile triple antiphospholipid antibody (aPL) positivity is associated with a higher risk of thrombosis, the clinical significance of single aPL positivity remains unclear. This study aimed to assess the prevalence, clinical characteristics, and cardiovascular disease (CVD) risk profile of persistently single aPL-positive primary antiphospholipid syndrome (PAPS) patients.MethodsWe conducted a retrospective analysis for APS patients from the APS ACTION registry with confirmed persistent single aPL positivity (after testing for lupus anticoagulant [LA], anticardiolipin [aCL] IgG/IgM, or anti-β2-glycoprotein I [aβ2GPI] IgG/IgM), defined by the Revised Sapporo APS Classification Criteria. Triple aPL-tested single aPL-positive patients with no APS classification were used as a control group. Demographics, clinical characteristics, aPL profiles, and adjusted Global APS Score (aGAPSS) were compared between two groups.ResultsAmong 233 PAPS patients tested, 84 (36%) had single aPL positivity: 67 (79%) LA positive, eight (10%) aCL IgG or IgM positive, and 9 (11%) aβ2GPI IgG or IgM positive. Among 97 aPL-positive patients with no APS classification, 22 (22.7%) had single aPL-positivity: nine LA positive, eight aCL IgG or IgM positive, and 5 aβ2GPI IgG or IgM positive. Single LA positivity was significantly more common in PAPS patients, whereas aCL IgM or aβ2GPI IgM positivity were significantly more common in those without APS classification. Historical thrombosis recurrence was observed in 26% of single aPL-positive PAPS patients, predominantly among those with LA positivity (86%).ConclusionsIn this international cohort of persistently aPL-positive individuals, 36% had single aPL positivity, mostly positive LA test. Although "single" aPL-positivity is traditionally considered as a lower-risk profile, findings highlight the importance of differentiating between single LA-positivity and single aCL/aβ2GPI positivity, and the need for individualized risk stratification.