aPLs seroconversion in antiphospholipid syndrome: from definition to clinical relevance

Antiphospholipid syndrome (APS) is an acquired coagulation disorder with an unclear pathogenesis, diagnosed in the presence of thrombotic events, obstetric complications, or non-thrombotic manifestations, alongside persistently detectable antiphospholipid antibodies. aPLs seroconversion, defined as the transition from persistent antibody positivity to sustained antibody negativity, is typically confirmed by at least two negative tests ≥12 weeks apart and maintained for over one year. This phenomenon is distinct from seronegative APS (SNAPS), in which patients present with APS-like clinical features but never fulfill laboratory criteria. Thrombotic risk remains significant in APS, particularly in patients with prior events or persistently elevated aPLs titers. Immunomodulatory therapies, such as hydroxychloroquine, rituximab, eculizumab, sirolimus, or other agents, may reduce antibody levels and contribute to improved outcomes, though evidence is limited. Among these, hydroxychloroquine is the most established agent, particularly in refractory or recurrent thrombotic cases, and is recommended as adjunctive therapy alongside anticoagulation in high-risk thrombotic and obstetric APS. While these therapies may allow cautious adjustments in anticoagulation for low-risk patients, anticoagulants should not be discontinued solely based on seroconversion or adjunctive treatment. Overall, immunomodulatory drugs should be considered strictly as adjuncts, with patient selection guided by clinical phenotype, thrombotic risk, and available evidence.