title: Factor V Leiden and hemophilia.
abstract: Several inherited prothrombotic risk factors have been identified so far. Among them, the factor V (FV) Leiden mutation causes a reduced ability of activated protein C to inactivate activated FV and is the most frequent genetic predisposing factor for venous thromboembolism. However, the high prevalence of FV Leiden (up to 15%) in the Caucasian population suggests that this mutation might confer an evolutionary survival advantage. Indeed, there is mounting evidence about the role of FV Leiden in modulating the clinical phenotype of some physiological and pathological conditions, including hemophilia. The existing literature on the interaction between FV Leiden and hemophilia-related factor VIII or IX mutations is analyzed in this review focusing on the clinical effects and possible pathogenic mechanisms. In summary, current evidence suggests that this prothrombotic mutation may compensate for the low factor VIII or IX levels, resulting in more efficient thrombin generation and ensuing attenuation of clinical symptoms. On the other hand, the association of this prothrombotic mutation with other acquired or inherited thrombophilic factors might overcome the congenital bleeding tendency in hemophiliacs, thereby increasing the risk of thrombotic complications.
authors.affiliation: Immunohematology and Transfusion Center, Department of Pathology and Laboratory Medicine, University Hospital of Parma, Parma, Italy. mfranchini@ao.pr.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Franchini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lippi
mesh_terms: D005165:Factor V / Q000235:genetics*; D006467:Hemophilia A / Q000235:genetics*; D006801:Humans; D009154:Mutation; D013927:Thrombosis / Q000235:genetics
chemical_list: C095381:factor V Leiden; D005165:Factor V