Tissue Factor Deficiency

Abstract: Tissue factor is now widely accepted to be the major physiological initiator of blood coagulation. The importance of this protein to normal haemostasis may be inferred from the clinical effects of factor VII deficiency and by the fact that congenital tissue factor deficiency has not been described. Tissue factor is a single polypeptide with an established amino acid sequence that may be divided into cytoplasmic, extracellular and transmembrane regions. There are no close structural similarities with other proteins although tissue factor may be a member of the cytokine receptor family. This paper reviews current knowledge of the role of tissue factor in the production of thrombin with particular reference to its expression, location, control and relevance to haemostasis.

Abstract: Exposure of blood to tissue factor (TF) activates the extrinsic (TF:FVIIa) and intrinsic (FVIIIa:FIXa) pathways of coagulation. In this study, we found that mice expressing low levels of human TF (≈1% of wild-type levels) in an mTF−/− background had significantly shorter lifespans than wild-type mice, in part, because of spontaneous fatal hemorrhages. All low-TF mice exhibited a selective heart defect that consisted of hemosiderin deposition and fibrosis. Direct intracardiac measurement demonstrated a 30% reduction (P < 0.001) in left ventricular function in 8-month-old low-TF mice compared with age-matched wild-type mice. Mice expressing low levels of murine FVII (≈1% of wild-type levels) exhibited a similar pattern of hemosiderin deposition and fibrosis in their hearts. In contrast, FIX−/− mice, a model of hemophilia B, had normal hearts. Cardiac fibrosis in low-TF and low-FVII mice appears to be caused by hemorrhage from cardiac vessels due to impaired hemostasis. We propose that TF expression by cardiac myocytes provides a secondary hemostatic barrier to protect the heart from hemorrhage.