From Wikipedia, the free encyclopedia
Factor VIII (FVIII) is an essential blood clotting factor also
known as anti-hemophilic factor (AHF). In humans, Factor VIII is
encoded by the F8 gene.
Defects in this gene results in hemophilia A, a well
known recessive X-linked coagulation
Factor VIII participates in blood
coagulation; it is a cofactor for factor IXa which, in the presence of
Ca+2 and phospholipids forms a complex that
converts factor X to the
activated form Xa. The Factor VIII gene produces two alternatively
spliced transcripts. Transcript variant 1 encodes a large glycoprotein, isoform
a, which circulates in plasma and associates with von
Willebrand factor in a noncovalent complex. This protein
undergoes multiple cleavage events. Transcript variant 2 encodes a
putative small protein, isoform b, which consists primarily of the
phospholipid binding domain of factor VIIIc. This binding domain is
essential for coagulant activity.
The gene for Factor VIII is located on the X chromosome (Xq28).
The gene for factor VIII presents an interesting primary structure,
as another gene is embedded in one of its introns.
FVIII is a glycoprotein procofactor. It has been found to
be synthesized and released into the bloodstream by the vascular,
glomerular, and tubular endothelium, and the sinusoidal cells of
the liver, though
there is still considerable ambiguity as to what the primary site
of release in humans is. In the circulating blood, it is mainly
bound to von Willebrand factor to form a
stable complex. Upon activation by thrombin, (Factor IIa), it dissociates from
the complex to interact with Factor IXa in 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
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 not affected by liver disease. In fact, levels
usually are elevated in such instances.
FVIII concentrated from donated blood plasma (Aafact), or alternatively recombinant FVIII can be given to hemophiliacs to restore hemostasis.
The transfer of a plasma byproduct into the blood stream of
a patient with hemophilia often led to the transmission of diseases
such as hepatitis B
and C and HIV before purification methods were
improved. Antibody formation to Factor VIII can also be a major
concern for patients receiving therapy against bleeding; the
incidence of these inhibitors is dependent of various factors,
including the Factor VIII product itself.[8
In the 1980s, some pharmaceutical companies such as Bayer sparked controversy by
continuing to sell contaminated factor
VIII after new heat-treated versions were available.
 In the early 1990s,
pharmaceutical companies began to produce recombinant synthesized factor products,
which now prevent nearly all forms of disease transmission during
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1d7p: Crystal structure of the c2 domain of human
factor viii at 1.5 a resolution at 1.5 A
1iqd: Human Factor VIII C2 Domain complexed to
human monoclonal BO2C11 Fab.