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Objectives To explore the relationship between autoantibodies targeting the phosphatidylserine/prothrombin (PS/PT) complex, markers of complement activation and clinical manifestations. The results will be compared to conventional antiphospholipid antibodies (aPL) in patients with primary and secondary antiphospholipid syndrome (APS).Methods We included 100 patients from the APS cohort at Karolinska University Hospital, Stockholm, Sweden, recruited between 2009 and 2022. Sixteen patients were purely obstetric APS without thrombotic manifestations, 12 were asymptomatic aPL carriers, 51 had primary APS (PAPS), and 37 had secondary APS (SAPS) ( table 1). aPS/PT, anti-b2 glycoprotein I (GPI), anti-cardiolipin (CL) antibodies of IgG and IgM isotype (ELISA) and complement components C3 and C4 were analyzed in samples collected at inclusion.Results We found an inverse correlation between aPS/PT IgG titers and C3 C4 levels (p=0.0347, p=0.0006). Patients positive for aPS/PT IgG (cut-off 30 units) had lower C3 and C4 levels (p=0.0138, p=0.0356). SAPS had lower levels of C4 compared to PAPS (0.16 ± 0.08 vs 0.21 ± 0.08, p=0.0110). SAPS presented with higher titers of aPS/PT IgG (71.45 ± 64.30 vs 43.36 ± 48.24, p=0.0215), but the percentage of patients positive for aPS/PT IgG was not significantly different between SAPS and PAPS (49% vs 39%, p=0.3779). aPS/PT IgG were more frequently positive (53% vs 31%, p=0.0264) and with higher titers (66.50 ± 61.86 vs 40.65 ± 48.77, p=0.0214) in patients affected by venous thrombosis compared to other APS clinical manifestations. aPS/PT IgM, anti-b2GPI IgG and IgM and anti-CL IgG and IgM were not associated with venous thrombosis.Abstract PO:01:023 Table 1Demographic, clinical and laboratory characteristics of APS cohortConclusions Novel antibodies aPS/PT IgG are inversely associated with C3 and C4 levels in APS, independently from treatment, Lupus Anticoagulant or triple positivity. aPS/PT IgG are positively associated with venous thrombosis, in contrast to aPS/PT IgM, anti-b2GPI IgG, IgM and anti-CL IgG, IgM that do not present this association. The increased thrombotic burden conveyed by the presence of aPS/PT IgG could be associated to complement activation.