Combined Genetic Defect (Homogeneity for Factor V Leiden and Heterogeneity for Prothrombin G20210A Allele), in a Young Patient, with Recurrent Deep Vein Thrombosis and Serious Postphlebitic Syndrome

Abstract

Just a few years ago, resistance to activated protein C (APCR) was reported to be of high significance representing a strong predisposing factor in the development of venous thrombosis (VT). A little while later, APCR was established to be the result of a point mutation of the factor V gene (factor V Leiden: a G-to-A transition at position 1691). Up to today, it is not certain whether factor V Leiden is in itself able to lead to VT, or whether it acts in synergy with other factors. Nevertheless, heterozygous subjects have a tenfold increase in the risk of VT when compared to general population, whereas the risk is 80 times greater in homozygous individuals. In 1996, a prothrombin gene mutation (prothrombin G20210A allele), which is a single-nucleotide G-to-A transition at position 20210 in the sequence of the 3'-untranslated region (3'UTR) on chromosome 11, was discovered. The presence of this mutant gene results in elevated plasma prothrombin concentrations, increasing the possibility for the development of VT. However, the coex- istence of these two abnormalities, as well as the clinical consequence, have not yet been studied. So far, only a few reports are found in the literature describing the coexistence of both mutations. The authors present a 25-year-old patient with a simultaneous double mutation of the FV and F II gene. The patient was homozygous for the factor V Leiden and heterozygous for the prothrombin G20210A allele. It is unclear whether the coexis tence of the two predisposes more to the development of VT than the summation of the two as independent factors.