High levels of endogenous PAI-1 are known to cause thrombophilia in humans due to marked inhibition of fibrinolysis [43], while over-expression of PAI-1 in liver of the Rf- embryo could represent an attempt to promote blood clotting in riboflavin-deficient embryos already experiencing marked hemophilia. This evidence concerns the gene SERPINE1 and Rare hereditary thrombophilia.