Background: Antiphospholipid syndrome (APS) is a thrombotic condition affecting young adults, characterized by thromboembolic events in the presence of circulating antiphospholipid antibodies (aPL). Recurrent thrombosis remains a significant clinical challenge in managing patients with APS, necessitating a comprehensive evaluation of the associated risk factors.
Objectives: To assess the frequency of recurrent thrombosis and identify risk factors associated with this condition in patients diagnosed with antiphospholipid syndrome.
Methods: This retrospective study included 100 patients diagnosed with APS, observed at the University Hospital of the Andes in Mérida, Venezuela, from 2013 to 2023. The cohort comprised 74 women and 26 men, aged between 16 and 60 years. Systemic lupus erythematosus (SLE) was diagnosed in 86% of the patients. Various aPLs were detected, including IgG/IgM antibodies against cardiolipin (aCL), β2-glycoprotein 1 (aβ2GP1), IgG antibodies against the domain 1 of β2-glycoprotein 1 (aβ2GP1-D1), and IgG/IgM antibodies against the phosphatidylserine/prothrombin complex (aPS/PT). The levels of aPLs were determined using enzyme-linked immunosorbent assay (ELISA) and chemiluminescent analysis (CLA).
Results: Recurrent thrombosis was observed in 33% of patients, with the primary cause of relapse attributed to the use of direct oral anticoagulants (DOACs). The duration of treatment with DOACs ranged from 6 to 24 months, which was not extended despite clear indications for prolonged therapy. Among the patients, 21 experienced recurrent thrombosis while on warfarin. Recurrent thrombotic events primarily manifested as arterial thromboembolism, with repeated strokes occurring in 18 patients. The level of positivity for aPL did not significantly impact outcomes; however, all patients were triple-positive for aPL IgG. Eight patients were found to have lupus anticoagulant (LA) at disease onset prior to anticoagulant therapy initiation. Notably, aPS/PT IgG exhibited the strongest association with recurrent thrombosis, with 19 patients testing positive for this marker. CLA detected aPL more frequently than ELISA, identifying 23 positive cases; however, recent classification criteria recommend the use of ELISA for aPL determination. Triple positivity for IgG aCL, IgG aβ2GP1, and IgG aβ2GP1-D1 according to CLA was also identified as a recurrent thrombosis risk factor, with the risk of relapse increasing more than threefold. Additionally, obesity significantly raised the risk of recurrent thrombosis by five times compared to patients without obesity (p = 0.041).
Conclusion: Recurrent thrombosis in APS is significantly associated with the presence of IgG aCL, IgG aβ2GP1, IgG aβ2GP1-D1, and IgG aPS/PT. The risk of recurrent thrombosis substantially increases with triple positivity for any combination of IgG aPL. The presence of IgG aPL, detected by both ELISA and CLA, influences the rate of recurrent thrombosis in APS. Furthermore, obesity emerged as a significant risk factor for recurrent thrombotic events. These findings highlight the need for thorough characterization of Latin American patients with APS to optimize management strategies.
REFERENCES: [1] Lambert M, Brodovitch A, Mège J-L, Bertin D, Bardin N. Biological markers of high risk of thrombotic recurrence in patients with antiphospholipid syndrome: A literature review. Autoimmun Rev [Internet]. 2024;23(6):103585. Disponible en:
[2] Kearon C, Parpia S, Spencer FA, Baglin T, Stevens SM, Bauer KA, et al. Antiphospholipid antibodies and recurrent thrombosis after a first unprovoked venous thromboembolism. Blood [Internet]. 2018;131(19):2151–60. Disponible en:
[3] Mittal P, Pacheco M, Trives-Folguera L, Rua J, Tohidi-Esfahani I, Cohen H, et al. Comparison of clinical and serological features in thrombotic antiphospholipid syndrome patients, with and without associated systemic lupus erythematosus, followed for up to 42 years: A single centre retrospective study. Lupus [Internet]. 2024;33(10):1082–8. Disponible en:
[4] Celinska-Löwenhoff M, Zabczyk M, Iwaniec T, Plens K, Musial J, Undas A. Reduced plasma fibrin clot permeability is associated with recurrent thromboembolic events in patients with antiphospholipid syndrome. Rheumatology (Oxford) [Internet]. 2018;57(8):1340–9. Disponible en:
[5] Egri N, Bentow C, Rubio L, Norman GL, López-Sañudo S, Mahler M, et al. Anti-phosphatidylserine/prothrombin antibodies at two points: Correlation with lupus anticoagulant and thrombotic risk. Front Immunol [Internet]. 2021;12:754469. Disponible en:
Acknowledgements: NIL.
Disclosure of Interests: None declared.
© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (