prothrombin deficiency results in embryonic and neonatal lethality in mice the conversion of prothrombin fii to the serine protease thrombin fiia is a key step in the coagulation cascade because fiia triggers platelet activation converts fibrinogen to fibrin and activates regulatory pathways that both promote and ultimately suppress coagulation however several observations suggest that fii may serve a broader physiological role than simply stemming blood loss including the identification of multiple g proteincoupled thrombinactivated receptors and the welldocumented mitogenic activity of fiia in in vitro test systems to explore in greater detail the physiological roles of fii in vivo fiideficient fii mice were generated inactivation of the fii gene leads to partial embryonic lethality with more than onehalf of the fii embryos dying between embryonic days 95 and 115 bleeding into the yolk sac cavity and varying degrees of tissue necrosis were observed in many fii embryos within this gestational time frame however at least onequarter of the fii mice survived to term but ultimately they too developed fatal hemorrhagic events and died within a few days of birth this study directly demonstrates that fii is important in maintaining vascular integrity during development as well as postnatal life