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 (FVHR2), on thrombin generation. Measurements were performed in platelet-poor plasma of individuals with factor VHR2 or factor VLeiden 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 FVHR2. The level of endogenous thrombin potential is in the same range as in samples of patients heterozygous or homozygous for FVLeiden. The results indicate that FVHR2 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 FVHR2 was studied. Copyright © 2005 S. Karger AG.