What is the role of factor VIII in the coagulation process?
Blood clot formation with coagulation factors is the body’s second line of defense against bleeding after initial platelet plug formation. It occurs through a series of enzyme reactions involving plasma protein cofactors. Factors V and VIII play essential roles in this process. Factor VIII accelerates the rate of cleavage of factor X by activated factor IX. This reaction takes place on a phos-pholipid surface where factor VIII increases the velocity of the reaction by several thousand-fold.
Factor VIII cannot, however, become part of the reaction, which includes a calcium-dependent complex of factor VIIIa, factor IXa, and phospholipid, until it is released from the von Willebrand factor that binds it. Factor VIII exists in the plasma as a complex with von Willebrand factor and as such cannot bind to phospholipid surfaces. However, the complex will concentrate itself at sites of vascular injury because von Willebrand factor itself binds to subendothelial matrix proteins and platelet aggregates. Thrombin or factor Xa cleaves factor VIII from this complex, freeing it to bind to the phospholipid surfaces of damaged cells and activated platelets.