Coagulation factor VIII, procoagulant component (hemophilia A)
PDB rendering based on 1d7p.
Available structures: 1d7p, 1iqd
Identifiers
Symbols	F8; AHF; DXS1253E; F8 protein; F8B; F8C; FVIII; HEMA
External IDs	OMIM: 306700 MGI: 88383 HomoloGene: 49153
Gene ontology Molecular function: • copper ion binding • calcium ion binding • oxidoreductase activity Cellular component: • extracellular region Biological process: • acute-phase response • cell adhesion • blood coagulation
RNA expression pattern
More reference expression data
Orthologs
	Human	Mouse
Entrez	2157	14069
Ensembl	ENSG00000185010	ENSMUSG00000031196
Uniprot	P00451	Q684Q7
Refseq	NM_000132 (mRNA) NP_000123 (protein)	NM_007977 (mRNA) NP_032003 (protein)
Location	Chr X: 153.72 - 153.9 Mb	Chr X: 71.43 - 71.64 Mb
Pubmed search	[1]	[2]

Factor VIII (FVIII) is an essential clotting factor. A deficiency of FVIII causes Hemophilia A, a bleeding disorder. 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. Defects in this gene results in hemophilia A, a common recessive X-linked coagulation disorder.¹

Genetics

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.².

Physiology

FVIII is a glycoprotein procofactor synthesized and released into the bloodstream by the endothelium. 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 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.³

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 B and C 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.⁴

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. In particular, some pharmaceutical companies such as Bayer sparked controversy by continuing to sell contaminated factor VIII after new heat-treated versions were available.⁵

See also

• Ryan White

References

Further reading

External links

• The Coagulation Factor VIII Protein
• MeSH Factor+VIII