Factor V G1691A and prothrombin G20210A in childhood spontaneous venous thrombosis - Evidence of an age-dependent thrombotic onset in carriers of factor V G1691A and prothrombin G20210A mutation

Risk factors for venous thrombosis in adults are the prothrombin (PT) G2021 0A, the factor (F) V G1691A mutations and hereditary deficiencies of protei n C, protein S and antithrombin. However, data are limited on the relevance of these risk factors for thrombosis in children and adolescents. We there fore investigated 119 patients aged 0-18 with spontaneous venous thrombosis and controls (n = 100) for the presence of the factor V G1691A mutation an d the prothrombin G20210A variant with respect to thrombotic onset and thro mbosis location. The following frequencies (patients vs. controls), odds ra tios (OR), 95%-confidence intervals (CI) and p-values were found: FV G1691A , 19.3% vs. 5%, OR/CI 4.55/1.66-12.5, p = 0.0038 and prothrombin G20210A, 8 .4% vs. 3%, OR/CI 2.96/0.8-11, p = 0.17. A combination of the FV G1691A mut ation with the PT G20210A variant was found in 3 children (2.5% of cases) b ut only once in the controls. With a median (range) age of 2 years (0-17), carriers of the FV mutation were significantly younger compared with patien ts carrying the PT variant (16 years: 0-18, p < 0.001). Vascular accidents in carriers of the FV mutation occurred in deep veins of the leg (n = 11), cerebral veins (n = 4), renal veins (n = 3) and portal veins (n = 2). Patie nts with the PT mutation showed spontaneous thrombosis in the majority of c ases in the deep veins of the leg (n = 5) and in the central nervous system (n = 2). Combined defects were found in a neonate with renal venous thromb osis and in two adolescents with deep vein thrombosis. Conclusion Data presented here suggest that the heterozygous FV mutation is the most commonly found prothrombotic risk factor responsible for spontane ous thrombosis during infancy and early childhood. In contrast, the PT G202 10A variant is likely to be more important during puberty and adolescence.