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

Risk factors for venous thrombosis in adults are the prothrombin G20210A and the factor V (FV) G1691A mutations and hereditary deficiencies of protein C, protein S and antithrombin. However, data are limited on the relevance of these risk factors for thrombosis in children and adolescents. We therefore 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 risk factors including the prothrombin G20210A mutation. The following frequencies of hereditary risk factors (patients versus controls), odds ratios (OR) and 95% confidence intervals (CI), or results of Fisher's exact test, respectively, 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 mutation was combined with the heterozygous FV G1691A mutation (2. 3%) or protein C deficiency (0.3%) in the patients, but not in the controls (prothrombin and FV mutation, P=0.0048; prothrombin and protein C deficiency, not significant). The carrier frequencies and ORs of all hereditary risk factors showed a non-significant trend toward higher prevalences in patients suffering spontaneous thrombosis, compared with those with an additional underlying disease. In conclusion, the prothrombin G20210A and the FV G1691A mutation, deficiencies of protein C, protein S, and antithrombin are important risk factors for venous thrombosis during childhood and adolescence.