Summary. Tissue factor pathway inhibitor (TFPI) inhibits tissue factor-induced coagulation. The major part of TFPI is releasable by heparin. We recently found eight patients with thrombosis and low levels of heparin-releasable TFPI in whom we investigated the TFPI gene for mutations. A transition of G to A coding for Valine264Methionine in the heparin-binding domain was found. The Val264Met polymorphism had an allele frequency of 3% in 96 healthy individuals. A silent polymorphism was identified in TFPI exon IV (T!C), which does not alter Tyrosine 56. Apart from Val264Met, which was detected in one out of the eight patients, no other mutations in the TFPI gene were found in patients with low heparin-releasable TFPI. Analysis of Val264Met in 317 patients with deep vein thrombosis (DVT) and 292 controls showed no association between Val264-Met and DVT. However, a study of total TFPI antigen levels in 122 DVT patients and 126 controls demonstrated an association between TFPI levels and venous thrombosis (P 0´0001). These results provide evidence for a relationship between venous thrombosis and total TFPI level as a possible risk factor, whereas they do not support a link between DVT and mutations in the nine exons of the TFPI gene.
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