Anti-prothrombin antibodies combined with lupus anticoagulant activity is an essential risk factor for venous thromboembolism in patients with systemic lupus erythematosus

Anti-prothrombin antibodies (anti-prothrombin) and anti-beta2-glycoprotein I antibodies (anti-beta2-GP I) are the most common and characterized anti-p hospholipid antibodies (aPL) detected using specific enzyme-linked immunoso rbent assay (ELISA) systems, Recently, lupus anticoagulant (LA) activity de tected by a phospholipid-dependent coagulation assay was reported to be ass ociated with anti-prothrombin and/or anti-beta2-GP I. Here we show that the co-existence of IgG anti-prothrombin and LA activity might be an essential risk factor for venous thromboembolism (VTE) in patients with systemic lup us erythematosus (SLE). We examined not only the levels of antibodies to pr othrombin and anti-beta2-GP I (both IgG and IgM isotypes) using an ELISA sy stem, but also LA activity detected using both diluted Russell's viper veno m time (dRVVT) and STACLOT LA test in 124 patients with SLE. The SLE patien ts were divided into four groups according to the results of ELISA and LA a ssay results for each aPL: group A, ELISA(+) and LA(+) group B, ELISA(+) an d LA(-); group C, ELISA(_) and LA(+) group D, ELISA(-) and LA(-). Regarding IgG anti-prothrombin, the prevalence of VTE was significantly higher in gr oup, A (16/35 cases, 45.7%, P < 0.001, Fisher's exact probability test) tha n in the other groups (B, 2/30, 6.7%; C, 1/22, 4.5%; D, 1/3 7, 2.7%). With respect to IgM anti-prothrombin and IgG or IgM anti-<beta>2-GP I, the preva lence of VTE was higher in both groups A and C than in group D, but no stat istical difference in prevalence was found between groups A and C. Multivar iate logistic regression analysis of risk, factors for VTE confirmed that t he co-existence of IgG anti-prothrombin and LA activity was the only signif icant risk factor for VTE (odds ratio, 19.13; 95% confidence intervals, 4.7 4-77.18).