The Influence of Tissue Factor and Tissue Factor Pathway Inhibitor Polymorphisms on Thrombin Generation in Stable Coronary Artery Disease

Abstract

In patients with stable coronary heart disease (n = 1,001) we investigated the influence of tissue factor (TF) and TF pathway inhibitor (TFPI) polymorphisms on thrombin generation in vivo, measured by prothrombin fragment (F) 1 and 2, and the potential to generate thrombin ex vivo, measured by the calibrated automated thrombogram assay. Additionally, circulating levels of TF and TFPI were correlated to the different parameters of thrombin generation. The TF 5466 and TFPI –399 polymorphisms associated with higher thrombin generation in vivo, the latter also with a prolonged lag time of the thrombin generation ex vivo(p < 0.05 for all).The TF –1812 TT and the TF –603 GG genotypes were associated with lower peak thrombin and a decreased average net rate of thrombin activation during the propagation phases (p ≤ 0.05), and the TFPI –33 TC genotype with prolonged lag time (p < 0.05) and additionally time to peak (p = 0.06). Strong correlations between TFPI levels, prothrombin fragment 1 and 2 as well as calibrated automated thrombogram parameters were observed.