Prothrombin G20210A gene mutation and further prothrombotic risk factors in childhood thrombophilia

Risk factors for venous thrombosis in adults are the prothrombin G20210A an d the factor V (FV) G1691A mutations and hereditary deficiencies of protein C, protein Sand antithrombin. However, data are limited on the relevance o f these risk factors for thrombosis in children and adolescents. We therefo re investigated 261 patients aged 0 to 18 (median 5.7 years, 48% male) with venous thrombosis and controls (n=370) for the presence of prothrombotic r isk factors including the prothrombin G20210A mutation. The following frequ encies of hereditary risk factors (patients Versus controls), odds ratios ( OR) and 95% confidence intervals (CI), or results of Fisher's exact test, r espectively, were found: prothrombin G20210A, 4.2% versus 1.1%, OR.CI 4.1/1 .3 to 12.8; FV G1691A, 31.8% versus 4.1%, OR/CI 11.0/6.2 to 19.7; protein C deficiency, 9.2% versus 0.8%, OR/CI 12.4/3.7 to 41.6, protein S deficiency , 5.7% versus 0.8%, OR/CI 7.5/2.1 to 26.0; antithrombin deficiency in 3.4% in the patients, but not in the controls, P=0.0003. The prothrombin mutatio n was combined with the heterozygous FV G1691A mutation(2.3%)or protein C d eficiency (0.3%) in the patients, but not in the controls (prothrombin and FV mutation, P=0.0048; prothrombin and protein C deficiency, not significan t). The carrier frequencies and ORs of all hereditary risk factors showed a non-significant trend toward higher prevalences in patients suffering spon taneous thrombosis, compared with those with an additional underlying disea se. In conclusion, the prothrombin G20210A and the FV G1691A mutation, defi ciencies of protein C, protein S, and antithrombin are important risk facto rs for venous thrombosis during childhood and adolescence.