Lupus anticoagulants and thrombosis: Clinical association of different coagulation and immunologic tests

The dilute Russell's viper venom time (dRVVT) and the kaolin clotting time (KCT) are two among the most commonly used coagulation tests for the detect ion of lupus anticoagulants. The dRVVT seems superior to the KCT in identif ying LA-positive patients at risk of thrombosis. However, this relationship is greatly influenced by both the source of reagents and the instrumentati on employed to carry out the assays. Therefore, 4 dRVVTs ("home-made" dRVVT , DVV test, Bioclot LA, LA Screen), and one KCT (Kaoclot) were performed in two centers and compared for their retrospective correlation with the thro mbotic complications of 72 patients with a previously established diagnosis of lupus anticoagulants. Two other assays ("home-made" KCT, and Colloidal Silica Clotting Time, CSCT) were performed in one of the two centers, and c ompared with Kaoclot for their clinical correlations in the same population of patients, 44 of whom (61%) had suffered from arterial and/or venous thr ombosis. A rather good degree of inter-laboratory and inter-assay correlati ons of the different tests was found. However, a statistically significant association with thrombosis was found only with the coagulation profile gen erated using the "homemade" dRVVT. When the commercially available dRVVTs w ere used, none of the coagulation profiles remained associated with thrombo sis. When the assays were analyzed separately, the association with thrombo sis was statistically significant for LA screen (p = 0.0019), DVV test (p = 0.0043), and Bioclot (p = 0.0255), and of borderline significance for the "home-made" dRVVT (p = 0.0503) in one center. This last assay was also sign ificantly associated with thrombosis in the other center (p = 0.0139). When venous and arterial thrombosis were considered separately, DVV test was st atistically associated with venous thrombosis in both centers (p = 0.0076 a nd p = 0.0187, respectively), and LA screen in one center (p = 0.0303). No dRVVT was found to correlate with arterial thrombosis. Kaoclot, Colloidal S ilica Clotting Time, and the "home-made" KCT did not correlate with thrombo sis. The prevalence of IgG and/or IgM antibodies to cardiolipin, beta2-glyc oprotein I and prothrombin were 74%, 86% and 85%, respectively. Increased t iters of IgG anticardiolipin antibodies were associated with arterial throm bosis (p = 0.0375), whereas IgM anti-beta2-glycoprotein I antibodies were a ssociated with venous thrombosis (p = 0.0433). In conclusion, these retrosp ective data support the notion that the dRVVT, rather than other coagulatio n or ELISA tests, are able to identify lupus anticoagulant-positive patient s at risk of thrombosis. This property appears common to several commercial ly available dRVVT kits, making this type of assay the ideal target of futu re efforts of laboratory standardization.