Tissue Factor Pathway Inhibitor, Hormone Replacement Therapy and risk of Venous Thromboembolism

Abstract

SUMMARY

Blood coagulation may lead to venous thromboembolism (VTE). Tissue factor pathway inhibitor (TFPI) is an important inhibitor of blood coagulation, however, the clinical significance or frequency of TFPI deficiency is yet not known. In the present study four known single nuclear polymorphisms (5 fUTR -287T ¨C, 5 fUTR -399C ¨T, intron 7 ¨33T-C, exon 9, 874G ¨A) of the TFPI gene has been investigated. Materials from two clinical trials (the EVTET and RET trials), including women previously suffering from VTE and healthy women, have been studied. All participants were randomized to different hormone replacement therapy (HRT) or placebo, i.e. high- and low dose estrogen or different formulas. A third group of healthy blood donors were also studied. All four TFPI polymorphisms were identified using Real Time Polymerase Chain Reaction, RT-PCR, and fluorescent hybridization probe melting curves. The results suggest that the 5 fUTR -287T ¨C and the intron 7 polymorphisms may protect against VTE, whereas 5 fUTR -399C ¨T may be associated with an increased risk of VTE. No clear association was seen between the exon 9 polymorphism and VTE, but this may due to the low frequency of the polymorphism. The study also suggests a considerable variance in the effect of the different TFPI polymorphisms on various estrogen formulas and doses, indicating that HRT should be individually adjusted.