Summary. Background: The characteristics and the clinical course of antiphospholipid syndrome (APS) in high-risk patients that are positive for all three recommended tests that detect the presence of antiphospholipid (aPL) antibodies have not been described. Methods: This retrospective analysis of prospectively collected data examined patients referred to Italian Thrombosis Centers that were diagnosed with definite APS and tested positive for aPL [lupus anticoagulant (LA), anti-cardiolipin (aCL), and anti-b2-glycoprotein I (b2GPI) antibodies]. Laboratory data were confirmed in a central reference laboratory. Results: One hundred and sixty patients were enrolled in this cohort study. The qualifying events at diagnosis were venous thromboembolism (76 cases; 47.5%), arterial thromboembolism (69 cases; 43.1%) and pregnancy morbidity (11 cases; 9.7%). The remaining four patients (2.5%) suffered from catastrophic APS. The cumulative incidence of thromboembolic events in the follow-up period was 12.2% (95%CI, 9.6-14.8) after 1 year, 26.1% (95%CI, 22.3-29.9) after 5 years and 44.2% (95%CI, 38.6-49.8) after 10 years. This was significantly higher in those patients not taking oral anticoagulants as compared with those on treatment (HR=2.4 95%CI 1.3-4.1; P < 0.003). Major bleeding associated with oral anticoagulant therapy was low (0.8% patient/years). Ten patients died (seven were cardiovascular deaths). Conclusions: Patients with APS and triple positivity for aPL are at high risk of developing future thromboembolic events. Recurrence remains frequent despite the use of oral anticoagulants, which significantly reduces the risk of thromboembolism.

Summary. Background: Determination of lupus anticoagulant (LA), anticardiolipin (aCL) and b2-Glycoprotein 1 (ab2GP1) antibodies is mandatory to classify patients with antiphospholipid syndrome (APS) into risk categories. Objectives: To measure relevant antibodies, considered to be those of the IgG isotype directed towards b2GP1 and particularly those directed to Domain 1 (Dm1) of the molecule. Patients/methods: In this cross-sectional study we measured IgG ab2GP1-Dm1 by a chemiluminescent immunoassay in a group of individuals initially positive for IgG ab2GP1 and classified as triple (LAC+, IgG aCL+, IgG ab2GP1+, n = 32), double (LAC-, IgG aCL+, IgG ab2GP1+, n = 23) or single positive (LA-, IgG aCL-, IgG ab2GP1+, n = 10). Results and conclusion: Geometric mean and standard deviation expressed as chemiluminescent units (CU) in triple, double and single positive groups were 273.0 AE 6.2, 18.2 AE 9.6 and 4.4 AE 2.2, respectively. The geometric mean obtained in 40 healthy subjects was 2.0 AE 2.0. Mean CU values were significantly different among groups and with respect to values found in 40 healthy subjects (P < 0.0001). Positive values of IgG ab2GP1-Dm1 (above 14.2 CU) were found in 45 individuals while 20 individuals (20/65 = 30.8%) positive for IgG ab2GP1 were negative for IgG ab2GPI-Dm1. There was a significant association between positive IgG ab2GP1-Dm1 and thromboembolic events (P = 0.001). Positive and negative values of IgG ab2GP1-Dm1 were consistently confirmed after 12 weeks, with only three low positive values being negative after 12 weeks. In conclusion, IgG ab2GP1-Dm1 seems a robust and reproducible test that in association with the classic tests may be useful in clinical practice in identifying individuals at high risk of developing thromboembolic events.

Our results show that high-risk subjects with triple-positive aPL profiles are identified early, at the time of the initial screening tests.

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The methods and the study design should be appropriate to achieve study results that are both scientifically valid and relevant to clinical practice.