Effect of the factor V Leiden mutation on the clinical expression of severe hemophilia A

To determine whether the factor V Leiden mutation is associated with decrea sed bleeding in individuals with severe hemophilia A, factor concentrate ut ilization, maximum annual number of bleeding episodes, and the prevalence o f hemophilic arthropathy between carriers and non-carriers of the factor V Leiden mutation were compared. Heterozygosity for the factor V Leiden mutat ion was found in 6 of 137 subjects (4.4%). Carriers of the factor V Leiden mutation utilized less factor concentrate (geometric mean: 310 vs. 1185 uni ts/kg/year) and had fewer bleeding episodes than non-carriers (proportion w ith 10 or fewer bleeding episodes in their worst year: 50 vs. 11%). However , the factor V Leiden mutation was not associated with the absence of arthr opathy. The intron 22 inversion mutation of the factor VIII gene was rested for in a subgroup of 80 subjects, but it was not found to be a significant variable for any of the bleeding endpoints. The results of this small stud y are consistent with the hypothesis that the factor V Leiden mutation impa rts a protective effect; however, a larger confirmatory study in which the factor VIII molecular defects can be controlled for is needed. Furthermore, most severe hemophiliacs who used fewer than 200 units/kg/year of factor c oncentrate or who had experienced 10 or fewer bleeding episodes per year di d not carry the factor V Leiden mutation, suggesting that the proportion of severe hemophiliacs whose mild clinical course can be attributed to the fa ctor V Leiden mutation is small.