Description
Factor VIII (FVIII) is a glycoprotein which circulates in plasma as a heterodimer composed of two polypeptide chains. These light and heavy chains are held together by a divalent metal ion bridge. In plasma FVIII is stabilized by hydrophobic and hydrophilic interactions with a 50-molar excess of von Willebrand factor (vWF). vWF promotes the association of the light and heavy chains of FVIII upon secretion. In the absence of vWF these chains are rapidly degraded. During activation, FVIII is released from vWF and converted to its active form FVIIIa, as a result of limited proteolytic cleavage by either thrombin or FXa. FVIIIa can then act as a key cofactor in the conversion of FX to FXa mediated by FIXa, in the presence of calcium and phospholipid.1
