A mong antiphospholipid antibodies, Lupus Anticoagulant (LAC) is recognized as the strongest risk factor for thromboembolic events or pregnancy morbidity. 1 The presence of LAC in a subject with previously documented thromboembolism or a significant history of pregnancy loss defines the Antiphospholipid Syndrome (APS). Some patients, however, are diagnosed with LAC without ever having experienced previous vascular thrombosis or pregnancy morbidity. The antiphospholipid antibody profiles of LAC positive patients with or without associated clinical features of APS have been evaluated by us in a multicenter study.Centers affiliated with Italian Federation of Thrombosis Centers (FCSA) were invited to identify consecutive LAC positive patients diagnosed over a 1-year period. Three hundred twenty-one recruited patients were contacted and after giving informed consent they underwent testing for LAC after at least 12 weeks from the first one using routine laboratory procedures. LAC was not confirmed by Thrombosis Centers in 19 patients (6 were children with previous acute infections). The plasma samples of 302 patients were sent to a central reference laboratory for final LAC confirmation and measurement of anticardiolipin (aCL) and anti-human 2-Glycoprotein I (a2GPI) antibodies by ELISA, as previously described. [2][3][4] On the basis of the results obtained, these patients were classified as category I when either IgG/IgM aCL or IgG/IgM a2GPI were also positive and as category IIa when LAC alone was positive. 5 Fisher exact test (using Woolf approximation) was performed for the comparisons of categorical variables. dRVVT ratios were compared by the unpaired student t test. aCL and a2GPI antibody values were compared by the nonparametric Mann-Whitney U test.Of the 231 patients whose positivity to LAC was confirmed by a central reference laboratory, 152 reported clinical events and had been diagnosed with APS (LAC/APS group) whereas 79 had no previous thromboembolic events or pregnancy morbidity (LAC/no APS group).The subjects in the LAC/APS group were slightly younger, and two-thirds in both groups were female. The ratio between the coagulation times of mixing to control plasma was used to compare LAC potency. Patients in the LAC/APS group had a 1.75Ϯ0.55 dRVVT ratio whereas those in the LAC/noAPS group had a 1.59Ϯ0.43 dRVVT ratio (Pϭ0.02).As shown in the Figure Of the 152 patients in LAC/APS group, 96 were also positive for IgG aCL or IgG a2GPI (71 had triple positivity) and were classified as category I. The rate of patients in category I in the LAC/APS group was significantly higher than that in the LAC/noAPS one (63% versus 30%, ORϭ3.3, 95%CI 2.2 to 7.0, PϽ0.001). On the other hand, the frequency of LAC positivity alone (classification category IIa) was significantly higher in the LAC/noAPS group (51% versus 28%, ORϭ2.7, 95%CI 1.5 to 4.7, PϽ0.001).With reference to a large number of patients with LAC, the LAC/APS group was found to have a stronger LAC potency and higher titers of IgG aCL and IgG a2GPI. This i...