Background APS ACTION “Registry” was created to study the natural course of disease over 10 years in persistently aPL-positive patients with/without other systemic autoimmune diseases. “Cluster analysis (CA)” is a data driven method that can group patients in a way that patients in the same group (cluster) are more similar to each other than to those in other groups.
Objectives To identify novel clinical phenotypes among aPL-positive patients.
Methods A web-based data capture system is used to store patient demographics, aPL-related history, and medications. The inclusion criteria are positive aPL based on the Revised Sapporo Classification Criteria at least twice within one year prior to enrollment. CA, using Ward's minimum-variance hierarchical method, was performed on the baseline characteristics of the first 500 patients. Thirty clinical data points were included in the CA to cover a broad spectrum of aPL-positive patients. To identify differences between clusters, ANOVA and χ2 test of independence were used. Tests were adjusted for all pairwise comparisons within a row using the Bonferroni correction to identify predominant and discriminant variables (Table).
Results After excluding missing data, 497 patients from 20 centers were analyzed. Three main exclusive clusters with different combinations of predominant demographic, clinical, and laboratory features were (Table): a) Cluster 1 – female patients with no other autoimmune diseases, but with venous thromboembolism (VTE) and triple-aPL positivity; b) Cluster 2 – female patients with lupus, VTE, aPL-related nephropathy, thrombocytopenia, hemolytic anemia, and positive lupus anticoagulant test; and c) Cluster 3 – older patients with arterial thrombosis, heart valve disease, livedo, skin ulcer, neurological manifestations, and cardiovascular risk factors.
Conclusions Based on our hierarchical cluster analysis, we identified three different clinical phenotypes of aPL-positive patients discriminated by antiphospholipid antibodies, lupus, or cardiovascular risk factors, respectively. Our results: a) support the heterogeneity of aPL-positive patients; and b) provide a foundation to understand disease mechanisms, create new approaches for APS classification, and ultimately to develop new management approaches.
Acknowledgements APS ACTION Members (*Top 5 Recruiting Centers): Australia: Sydney (B Giannakopoulos, S Krilis); Brazil: Rio de Janeiro (G de Jesus, R Levy), São Paulo (R Rosa*, D Andrade*); Canada: Quebec (PR Fortin); China: Beijing (Z Zhang); France: Nancy (S Zuily, D Wahl); Greece: Athens (M Tektonidou*); Italy: Brescia (C Nalli, L Andreoli, A Tincani), Milan (CB Chighizola, PL Meroni), Padova (A Banzato*, V Pengo*); Jamaica: Kingston (K De Ceulaer); Japan: Sapporo (T Atsumi); Lebanon: Beirut (I Uthman); Netherlands: Utrecht (RH Derksen, PG de Groot); Spain: Barakaldo (G Ruiz Irastorza*), Barcelona (I Rodriguez-Pinto, G Pons-Estel, R Cervera), Madrid (E Rodriguez); United Kingdom: London (I Mackie, H Cohen; and S Sciascia, ML Bertolaccini, M Cuadrado, M Khamashta); USA: Baltimore (M Petri), Boston (M Barbhaiya), Chapel Hill (R Roubey), Durham (T Ortel), Galveston (E Gonzalez, R Willis), New York City (SR Levine; J Rand; and D Erkan*, J Salmon*, MD Lockshin*), Salt Lake City (W Branch).
Disclosure of Interest None declared