Antiphospholipid Antibodies and Atrial Fibrillation: Clinical Implications and the TaPL-AF Study Design

Antiphospholipid antibodies (aPL) are a heterogeneous group of autoantibodies that target phospholipids and phospholipid-binding proteins, and are identified clinically by anticardiolipin, anti-β2-glycoprotein I, or lupus anticoagulant assays. While aPL are a well-established mediator of thrombosis through both proinflammatory and prothrombotic pathways, the role of aPL in arrhythmogenesis including atrial fibrillation (AF) and their association with AF-related thromboembolic outcomes remains poorly defined. In small observational studies, testing positive for aPL has been reported in up to 20% of patients with AF and has been associated with a higher risk of ischemic stroke and other thromboembolic events. In this mini-review, in addition to sharing a succinct summary on prevalence and pathogenicity of aPL in various vascular and thrombotic conditions, we specifically summarize the existing body of literature investigating the association between aPL and AF prevalence and clinical outcomes. Furthermore, we describe the rationale and study design of the TaPL-AF (Thrombophilia with aPL in Atrial Fibrillation) study, an ongoing investigation leveraging Mass General Brigham (MGB) Biobank data to provide evidence on the incidence and prognostic relevance of aPL positivity in AF and explore the impact of aPL on the effectiveness of direct oral anticoagulants in preventing thromboembolic events. These efforts aim to define the clinical relevance of aPL in AF, including their potential role in refining thromboembolic risk stratification and guiding anticoagulation strategies.