Identification of phenotypes in thrombotic primary antiphospholipid syndrome using cluster analysis: a step toward personalized medicine

Abstract

Background: Thrombotic risk in primary antiphospholipid syndrome (APS) is a result of complex, yet undefined, interactions among multiple factors. While long-term anticoagulation reduces thrombotic complications, its efficacy varies, with thrombosis recurrence rates ranging from 5% to 20% within 2 years. Emerging therapies may benefit specific APS subgroups, although identifying and stratifying these groups remains a significant challenge.

Objectives: To identify specific phenotypic subgroups of thrombotic primary APS based on clinical and laboratory characteristics to provide insight for both personalized diagnostic and therapeutic strategies.

Methods: Multicenter retrospective cohort study including 663 patients with thrombotic primary APS who were followed in Brazil, Israel, and Mexico (2018-2023). Hierarchical cluster analysis categorized patients based on demographics, thrombotic characteristics, comorbidities, and laboratory data.

Results: Cluster analysis identified 3 distinct phenotypes. Cluster 1 (n = 348) included older patients (median age 43 years) with high cardiovascular risk factors (hypertension, diabetes, and dyslipidemia) and predominantly arterial thrombosis (53%, P < .001). Cluster 2 (n = 119) included younger patients (median age 35 years) with high recurrence rates (71%, P < .001) of venous thromboembolism (80%, P < .001) and higher anticardiolipin prevalence (29%, P < .001). Cluster 3 (n = 196) featured the youngest patients (median age 29 years), predominantly triple antiphospholipid antibody positive (98.5%, P < .001), with complement consumption (C3: 17%, P = .003), thrombocytopenia (12%, P = .05), and venous thrombosis (73%, P < .001).

Conclusion: This study identified 3 distinct phenotypes of thrombotic primary APS, each characterized by the predominance of cardiovascular risk factors, hypercoagulability, or immunologic derangements. The findings provide a basis for developing personalized management strategies to improve patient outcomes.

Keywords: antiphospholipid syndrome; autoantibodies; individualized medicine; risk factors; thrombosis.