Factor IX (F.IX, Christmas Factor) is a vitamin K-dependent glycoprotein produced in the liver. Plasma concentration of F.IX is normally around 5ug/ml (87nM) in plasma. The biological importance of F.IX is demonstrated in Haemophilia B (Christmas disease), an X-linked congenital bleeding disease resulting from a quantitative (low activity and low antigen) or qualitative (low activity and normal antigen) defect in F.IX function. In its zymogen form F.IX is a single chain molecule of 55kD. It contains two EGF-like domains and an amino-terminal domain containing 12 y-carboxy-glutamic acid (Gla) residues. These Gla residues allow F.IX to bind divalent metal ions and participate in calcium-dependent binding interactions. The activation of F.IX occurs by limited proteolysis in the presence of calcium by activated factor XI (FXIa) and/or by a complex of VIIa/tissue factor/phospholipid and activated Factor X between residues Arg146- Ala147 and between Arg180-Val181. The terminal activated product in either case is F.IXaB, a two-chain enzyme consisting of a heavy chain (28kD), a light chain (18kD) and an activation peptide product of 11kD. F.IX can also be cleaved into inactive products by thrombin and by elastase. The activity of F.IXaB in plasma is inhibited by antithrombin and this inhibition is accelerated approximately 1000-fold in the presence of optimal concentrations of heparin.