Factor IX (FIX, Christmas Factor) is a vitamin K-dependent glycoprotein produced in the liver. Plasma concentration of FIX is normally around 5ug/ml (87nM) in plasma. The biological importance of FIX is demonstrated in Hemophilia 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 FIX function. In its proenzyme or zymogen form FIX is a single chain molecule of 55kD It contains two EGF-like domains and an amino-terminal domain containing 12 gamma-carboxy- glutamic acid (Gla) residues. These Gla residues allow FIX to bind divalent metal ions and participate in calcium-dependent binding interactions. The activation of FIX 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 aa146-147 and between aa180-181. The terminal activated product in either case is FIXa beta, a two-chain enzyme consisting of a heavy chain (28kD), a light chain (18kD) and an activation peptide product of 11kD. FIX can also be cleaved into inactive products by thrombin and by elastase. The activity of FIXa beta in plasma is inhibited by antithrombin and this inhibition is accelerated 1000-fold in the presence of optimal concentrations of heparin.