Gene targeting in hemostasis. tissue factor pathway inhibitor

Abstract

Factor VII (FVII), in concert with its natural cofactor and receptor, Tissue Factor (TF), initiates the process of blood coagulation following vascular injury. Mice completely deficient in FVII were generated via specific deletion of exons 2 to 8, thus deleting the entire coding region of the mature protein. In contrast to the early lethality observed in TF-deficient embryos (TF-/-), embryos deficient in FVII (FVII-/-) developed normally, without incidence of hemorrhage. However, FVII-/- neonates succumbed to either early intraabdominal or intracranial hemorrhage in later life.

Aetiology of Venous Thrombosis

“…Experiments on genetically modified mice with TFPI gene disruption showed that they die prematurely in embryonic stage and before birth due to haemorrhagic and intravascular thrombi. Human embryos with TFPI deficiency may suffer a similar problem and this may explain why no cases with TFPI deficiency has been identified so far (Broze, 1998;Chan, 2001;Maroney & Mast;2008).…”