Factor VIII

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coagulation factor VIII
Identifiers
Symbol	F8 F8C
HUGO	3546
Entrez	2157
OMIM	306700
RefSeq	NM_000132
UniProt	P00451
Other data
Locus	Chr. X q28

Factor VIII (FVIII) is an essential clotting factor. The lack of normal FVIII causes Hemophilia A, an inherited bleeding disorder.

[edit] Genetics

The gene for Factor VIII is located on the X chromosome (Xq28).

[edit] Physiology

FVIII is a glycoprotein procofactor synthesized and released into the bloodstream by the vascular endothelium. 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.

Factor VIII is synthesized predominantly in the vascular endothelium and is not affected by liver disease. In fact, levels usually are elevated in such instances. (Rubin, Ronald N. Rubin. Hematologic Pathophysiology. Hayes Barton Press, 1998. 4.8.1). <vbk:1-889325-04-X#outline(4.8.1)>

[edit] Therapeutic use

FVIII concentrated from donated blood plasma (Aafact), or alternatively recombinant FVIII can be given to hemophiliacs to restore hemostasis. Thus, FVIII is also known as Anti-Hemophilic Factor.

The transfer of a plasma byproduct into the blood stream of a patient with hemophilia often led to the transmission of diseases such as HIV and hepatitis before purification methods were improved. 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.

The side effect of recombinant products have not yet been fully determined. Since recombinant products have been in the market, there have been some case studies where patients developed anti-bodies against the recombinant products. Putting such patients back on the plasma-derived factor have been successful in reversing this effect.