Antiphosphatidylserine/prothrombin antibodies define a high-risk antiphospholipid syndrome profile associated with organ damage

Objectives Antiphosphatidylserine/prothrombin (aPS/PT) antibodies are promising non-criteria aPLs associated with antiphospholipid syndrome (APS) manifestations. Their influence on long-term outcomes and damage remains uncertain. To assess aPS/PT antibodies association with accrual damage and severe APS disease phenotypes, focusing on their potential for risk stratification. Methods This single-centre cohort study involved 163 patients who fulfilled the 2023 ACR/EULAR APS criteria. IgG/IgM aPS/PT, aCL, and anti-β2GPI antibodies were measured by commercial ELISA. Lupus anticoagulant (LA) was detected in accordance with the ISTH-SSC recommendation. Clinical data covered macrovascular, microvascular, obstetric, and hematologic manifestations. Damage was assessed using DIAPS. Results aPS/PT IgG and IgM were positive in 46.0 % and 65.6 %, respectively. aPS/PT IgG positivity was linked to microvascular involvement (58.7 % vs. 34.1 %, p=0.002), obstetric APS (57.4 % vs. 24.6 %, p<0.0001), valvular disease (17.3 % vs. 4.6 %, p=0.008), and thrombocytopenia (37.3 % vs. 12.5 %, p<0.0001). aPS/PT IgM positivity was also associated with microvascular APS (p=0.006), obstetric morbidity (p=0.02), and thrombocytopenia (p=0.01). In multivariable analysis, quadruple aPL positivity (LA + aCL + anti-β2GPI + aPS/PT) was independently linked to damage (OR 4.3, 95 % CI 1.3–14.5; p=0.02), with no other factors remaining significant. Conclusions Both IgG and IgM aPS/PT antibodies are associated with severe APS features, including microvascular and obstetric issues, as well as overall organ damage. Adding aPS/PT to standard aPL tests finds a subgroup of quadruple-positive APS patients at higher risk of damage. These results could help guide personalized APS management.