Effect of the Factor V Leiden Mutation on the Clinical Expression of Severe Hemophilia A

Abstract

SummaryTo determine whether the factor V Leiden mutation is associated with decreased bleeding in individuals with severe hemophilia A, factor concentrate utilization, maximum annual number of bleeding episodes, and the prevalence of hemophilic arthropathy between carriers and non-carriers of the factor V Leiden mutation were compared. Heterozygosity for the factor V Leiden mutation 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 units/kg/year) and had fewer bleeding episodes than non-carriers (proportion with 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 arthropathy. The intron 22 inversion mutation of the factor VIII gene was tested 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 study are consistent with the hypothesis that the factor V Leiden mutation imparts 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 concentrate or who had experienced 10 or fewer bleeding episodes per year did not carry the factor V Leiden mutation, suggesting that the proportion of severe hemophiliacs whose mild clinical course can be attributed to the factor V Leiden mutation is small.

Targeted exome analysis in patients with rare bleeding disorders: data from the Rare Bleeding Disorders in the Netherlands study

“…Median ISTH-BAT scores of 6 patients with a prothrombotic variant were lower than the overall RBiN population (2.5 vs 10). Co-occurrence of a prothrombotic variant may ameliorate bleeding risk in patients with RBDs, as these variants have been associated with lower annual bleeding rates and delayed onset of first bleeding in patients with hemophilia [ 49 , 50 ]. Investigating prothrombotic variants (including polymorphisms) in a larger cohort of RBDs would be valuable in understanding their potential impact on RBDs.…”

Thrombotic Disease in Hemophilic Patients: Is This a Paradox in a State of Hypocoagulability?

“…Lee et al conducted a study on 137 subjects which reported that patients with an FVL mutation had lower factor concentrate consumption (mean: 310 vs. 1185 U/kg/y) and fewer bleeding episodes. Other studies have also suggested that individuals with hemophilia who carry the FVL mutation may experience a reduction in the development of hemophilic arthropathy, lower factor concentrate utilization, a delayed occurrence of the first symptomatic bleeding, and reduced bleeding symptoms compared to those without this mutation [19,35,56,57].…”