We recently reported the LA, IgG binding to protein S and transient protein S deficiency in 7 children with acute VZV complicated by purpura fulminans, DIC or large vessel thrombosis. A prospective study of previously healthy children with acute VZV was initiated. Children with a past history (> 1 year) of VZV served as a reference group. Laboratory evaluation included the APTT and dilute Russell Viper Venom time (dRVVT) to screen for the LA, with phospholipid correction for confirmation. Antiphospholipid lipid antibodies(APA), anticardiolipin antibodies, IgG and IgM binding to prothrombin, protein C, and protein S and the prothrombin fragment F 1+2 were determined in ELISA assays. Free protein S was measured using PEG 8000 and Laurell rocket technique. To date, we have studied 26 children with acute VZV and 20 children with past VZV. In comparison to the reference group, children with acute VZV showed the following: prolonged APTT (41.8 vs. 33.9 sec, p=0.0002), prolonged dRVVT (45.8 vs. 32.6 sec, p <0.0001), lower concentration of free protein S(0.66 vs. 0.87 U/mL, p=0.018), elevated F 1+2 (2.66 vs. 0.98 nM/L, p<0.0001), increased IgG binding to prothrombin (0.147 vs. 0.009 U, p=0.0058), protein C (0.098 vs. 0.004 U, p=0.0043), and protein S (0.220 vs. 0.022, p=0.0044) as well as IgM binding to prothrombin (0.115 vs. 0.047 U, p=0.076), protein C (0.110 vs. 0.029 U, p=0.0149), and protein S (0.188 vs. 0.037 U, p= 0.0059). Regression analysis showed that concentration of free protein S correlated inversely with IgG and IgM binding to protein S as well as concentration of F 1+2 (p<0.0001 for each). Of the 26 children with acute VZV, 20 were confirmed positive for the LA, 16 had an APA, and 8 had anticardiolipin antibodies. These results suggest that the immune response to VZV includes formation of antibodies which react against phospholipids and multiple vitamin K-dependent proteins, especially protein S. Increased thrombin activation found in the presence of antibodies to phospholipid and protein S during acute VZV infection in children suggests that these antibodies may cause hypercoagulability.
