One of a series of enzymes present in the blood which controls the clotting process. Sufferers from classical haemophilia lack this factor, and their blood therefore lacks the capacity to clot. They are treated by intravenous administration of factor VIII that has been separated from fresh blood. This process carries the risk of transferring infections such as AIDS from the blood donor. In future, haemophiliacs may be cured by gene therapy, which would enable them to make factor VIII themselves. A rarer form of haemophilia results from the absence of factor IX (the Christmas factor, named after the first patient studied in detail with this deficiency), which can similarly be replaced.
Factor VIII (FVIII) is an essential clotting factor.
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. 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.
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.
Factor VIII is synthesized predominantly in the vascular endothelium and is not affected by liver disease.
Therapeutic use
FVIII concentrated from donated blood plasma, or alternatively recombinant FVIII can be given to hemophiliacs to restore hemostasis. In the early 1990s, pharmaceutical companies began to produce recombinant synthesized factor products, which now prevent nearly all forms of disease transmission during replacement therapy.
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