Factor VIII
From Free net encyclopedia
Factor VIII (FVIII) is an essential clotting factor. The lack of normal FVIII causes Hemophilia A, an inherited bleeding disorder.
Genetics
The gene for Factor VIII is located on the X chromosome (Xq28).
Physiology
FVIII is a glycoprotein procofactor synthesized and released into the bloodstream by the liver. In the circulating blood, it is mainly bound to von Willebrand factor (vWF, also known as Factor VIII-related antigen) to form a stable complex. Upon activation by thrombin or factor Xa, it dissociates from the complex to interact with Factor IXa the coagulation cascade. It is a cofactor to Factor IXa in the activation of Factor X, which, in turn, with its cofactor Factor Va, activates more thrombin. Thrombin cleaves fibrinogen into fibrin which polymerizes and crosslinks (using Factor XIII) into a blood clot.
No longer protected by vWF, activated FVIII is proteolytically inactivated in the process (most prominently by activated Protein C and Factor IXa) and quickly cleared from the blood stream.
Therapeutic use
FVIII harvested from donated blood (or more likely, purchased blood plasma) or Recombinant FVIII can be given to hemophiliacs to restore hemostasis. Thus, FVIII is also known as Anti-Hemophilic Factor.
This transfer of a plasma biproduct into the blood stream of a hemophiliac often lead to the transmission of diseases such as HIV and hepatitis. In the early 1990s, pharmaceutical companies began to produce synthesized factor products, which now prevent nearly all forms of disease transmission during replacement therapy.