The role of different aPL subpopulations in the lupus anticoagulant phenomenon

The lupus anticoagulant (LA) phenomenon represents a paradoxical prothrombotic state characterised by inhibition of phospholipid-dependent coagulation assays in vitro, despite a strong association with thrombosis and pregnancy morbidity in vivo. LA is a central laboratory criterion for the diagnosis and risk stratification of antiphospholipid syndrome and reflects the functional activity of heterogeneous antiphospholipid antibodies (aPL) targeting phospholipid-binding plasma proteins. Among these, LA shows the strongest association with thrombotic outcomes. LA detection relies on clotting-based assays, principally the dilute Russell's viper venom time and LA-sensitive activated partial thromboplastin time, interpreted within a standardised three-step framework. However, LA testing remains technically challenging, particularly in anticoagulated patients, and is influenced by biological variability and assay heterogeneity. This review summarises the mechanisms by which distinct aPL subpopulations generate LA activity and their pathophysiological and clinical implications.