A Comparison of Lupus Anticoagulant–Positive Patients With Clinical Picture of Antiphospholipid Syndrome and Those Without

Abstract

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 (a␤2GPI) 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 a␤2GPI 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 a␤2GPI 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 a␤2GPI (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 a␤2GPI. This i...

Antiphospholipid syndrome: interpretation of laboratory data

“…False positivity for this test can often be encountered in elderly patients or when LA is mild in potency. In our hands, sole positivity for LA (classification category IIa) is not associated with thrombosis [3], or with clinical manifestations of APS [12]. Similar conclusions were drawn from the Leiden thrombophilia case-control study [13], where LA positivity in the absence of ab2GPI or antiprothrombin antibodies was not associated with an augmented risk for deep vein thrombosis (odds ratio, 1.3; 95% confidence interval, 0.3-6.0).…”

Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study

“…22 However, it is mandatory to know the complete aPL profile of patients/carriers as in our hands the sole positivity for LA is not associated with thrombosis, 6 or with clinical manifestations of APS. 23 Similar conclusions were drawn from the Leiden thrombophilia casecontrol study, 24 where LA positivity in the absence of anti-␤ 2 GPI or antiprothrombin antibodies was not associated with an augmented risk for deep vein thrombosis (odds ratio ϭ 1.3; 95% CI, 0.3-6.0). It must be underlined here that, in triple-positive patients, LA potency is strong and the titer of aCL (mostly IgG) and anti-␤ 2 GPI antibodies is high.…”

“…It must be underlined here that, in triple-positive patients, LA potency is strong and the titer of aCL (mostly IgG) and anti-␤ 2 GPI antibodies is high. 7,23 Most carriers of triple positivity in this study (64%) were not prescribed antithrombotic prophylaxis, and the remaining were given low-dose aspirin. However, aspirin use did not result in a significant reduction either of total TEs or of the sole arterial thromboembolism.…”

Challenges in the Diagnosis of the Antiphospholipid Syndrome

“…Patients positive only for aCL and anti-␤2GPI antibodies without any history of TEC present with obstetric complications only (46 ). Isolated LAC positivity is present more frequently in subjects without clinical events and may even be false positive in elderly patients or when diagnosed for the first time (50,51 ).…”