The presence of non-criteria manifestations negatively affects the prognosis of seronegative antiphospholipid syndrome patients: a multicenter study.

Abstract

Background: Seronegative antiphospholipid syndrome (SN-APS) is often defned as the presence of APS criteria manifestations, negative antiphospholipid antibodies (aPL), and coexistence of APS non-criteria manifestations. Nevertheless, the impact of these non-criteria features is still unclear. On a diferent note, the relevance of one single aPL positive determination in patients with APS manifestations is another domain with limited evidence. We aim to compare the course of SN-APS and single-positive aPL (SP-aPL) patients with that of individuals with APS manifesta‑ tions without non-criteria features/aPL positivity (controls). Methods: Retrospective analysis of patients with thrombosis/obstetric morbidity assessed in two European hospi‑ tals between 2005 and 2020. Patients were divided into SN-APS, SP-aPL, and control groups. Clinical characteristics, comorbidities, and therapies were compared. Results: A total of 82 patients were included in the SN-APS group, 88 in the SP-aPL group, and 185 in the control group. In Cox regression model, SN-APS displayed more thrombosis recurrence than controls (HR 3.8, 95% CI 2.2-6.5, p<0.001) even when adjusting for the presence of hereditary thrombophilia, systemic lupus erythematosus, or con‑ traceptive hormonal treatment. In SP-aPL, the diference in thrombosis recurrence did not reach statistical signifcance (p=0.078). Indefnite anticoagulation (p<0.001 and p=0.008, respectively) and vitamin K antagonist (VKA) use (p<0.001 in both cases) were more common in SN-APS/SP-aPL. Conclusion: SN-APS displayed more thrombosis recurrence, indefnite anticoagulation, and VKA use than controls without non-criteria manifestations. The presence of such features in patients with thrombosis and negative aPL may negatively impact their clinical course. Keywords: Antiphospholipid syndrome, Antiphospholipid antibodies, Seronegative, Single positive, Non-criteria manifestations