title: Influence of factor V HR2 on thrombin generation and clinical manifestation in rare bleeding disorders.
abstract: In this study we investigated the influence of the presence of the factor V HR2 haplotype, defined by the factor V gene mutation H1299R (FV(HR2)), on thrombin generation. Measurements were performed in platelet-poor plasma of individuals with factor V(HR2) or factor V(Leiden) in comparison to a control group carrying none of these mutations. Coagulation was triggered by low concentrations of recombinant tissue factor in the presence of activated protein C. Thrombin generation was monitored by a fluorogenic substrate. The endogenous thrombin potential was calculated from the obtained curves. As a result we observed an increased thrombin generation both for individuals heterozygous and homozygous for FV(HR2). The level of endogenous thrombin potential is in the same range as in samples of patients heterozygous or homozygous for FV(Leiden). The results indicate that FV(HR2) plays a role as a risk factor for venous thrombosis in homozygous patients through an increased thrombin generation. The association between different clinical manifestations in individuals with FVII deficiency and endogenous thrombin potential and the presence of FV(HR2) was studied.
authors.affiliation: Department of Human Genetics, EMA University of Greifswald, Greifswald, Germany. strey@uni-greifswald.de
authors.forename: Rüdiger F
authors.initials: RF
authors.lastname: Strey
authors.forename: Annelie
authors.initials: A
authors.lastname: Siegemund
authors.forename: Thomas
authors.initials: T
authors.lastname: Siegemund
authors.forename: Christine
authors.initials: C
authors.lastname: Schubert
authors.forename: Gudrun
authors.initials: G
authors.lastname: Schuster
authors.forename: Karin
authors.initials: K
authors.lastname: Wulff
authors.forename: Falko H
authors.initials: FH
authors.lastname: Herrmann
mesh_terms: D001778:Blood Coagulation Disorders / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D005165:Factor V / Q000235:genetics* / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D012307:Risk Factors; D013917:Thrombin / Q000378:metabolism*
chemical_list: C095381:factor V Leiden; D005165:Factor V; D013917:Thrombin