Factor VIII

Title: Factor VIII
CAS Registry Number: 9001-27-8
CAS Name: Blood-coagulation factor VIII
Additional Names: antihemophilic globulin; antihemophilic factor A; AHG; AHF
Trademarks: Alphanate (Alpha Ther.); Hemofil-M (Baxter); Humate-P (Centeon); Koate-HP (Bayer); Monoclate-P (Centeon); Nordiocto (Nordisk); Profilate (Alpha Ther.)
Literature References: Crucial, nonenzymatic cofactor in the intrinsic coagulation pathway leading to the localized generation of thrombin. Deficiency results in the bleeding disorder known as hemophilia A or classical hemophilia. Factor VIII is an X-linked gene product synthesized by hepatocytes. Mature, single chain protein contains 2332 amino acid residues; mol wt 265 kDa. Released into the circulation as a set of heterodimers that rapidly interact with von Willebrand factor to form a stable, noncovalent complex; present at extremely low concn in plasma. Converted by thrombin into a heterotrimer (factor VIIIa) that accelerates the activation of factor X by factor IXa. Inactivated by protein C. Identification in plasma: T. Addis, J. Pathol. Bacteriol. 15, 427 (1911). Role in hemostasis: A. J. Patek, Jr., F. H. L.Taylor, J. Clin. Invest. 16, 113 (1937). Isoln and characterization of human factor VIII: E. J. Hershgold et al., J. Lab. Clin. Med. 77, 185 (1971). Purification and properties of bovine: G. A. Vehar, E. W. Davie, Biochemistry 19, 401 (1980). Characterization of the human factor VIII gene: J. Gitschier et al., Nature 312, 326 (1984). Series of articles on cloning, expression, and structure: ibid. 330-347. Review of bioregulation: R. J. Kaufman, Annu. Rev. Med. 43, 325-339 (1992). Review of production methods and clinical use in treatment of factor VIII deficiency: J. C. Gill, Semin. Thromb. Hemostasis 19, 1-12 (1993). Review of biosynthesis, structure and function: P. Lollar, Adv. Exp. Med. Biol. 386, 3-17 (1995); P. J. Lenting et al., Blood 92, 3983-3996 (1998).
Derivative Type: Kogenate
CAS Registry Number: 169149-90-0
Literature References: Recombinant human factor VIII produced in baby hamster kidney cells. Review of manufacturing process: H.-D. Hörlein, Prog. Biotechnol. 9, 731-734 (1994). Clinical trial in treatment of hemophilia: E. Aygören-Pürsün et al., Thromb. Haemostasis 78, 1352 (1997).
Derivative Type: Recombinate
Literature References: Recombinant human factor VIII produced in Chinese hamster ovary cells. Review of manufacturing process: E. Gomperts et al., Transfus. Med. Rev. 6, 247-251 (1992). Clinical trial in treatment of hemophilia: G. C. White II et al., Thromb. Haemostasis 77, 660 (1997).
Therap-Cat: Antihemophilic factor (human).
Keywords: Hemostatic; Antihemophilic Factor.
Factor X Factor XI Factor XII Factor XIII Fadrozole

Coagulation factor VIII, procoagulant component

PDB rendering based on 2R7E.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols F8 (; AHF; DXS1253E; F8B; F8C; FVIII; HEMA)
External IDs OMIM: 300841 MGI: 88383 HomoloGene: 49153 ChEMBL: 3143 GeneCards: F8 Gene
RNA expression pattern
PBB GE F8 205756 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2157 14069
Ensembl ENSG00000185010 ENSMUSG00000031196
UniProt P00451 Q06194
RefSeq (mRNA) NM_000132 NM_001161373
RefSeq (protein) NP_000123 NP_001154845
Location (UCSC) Chr HG1497_PATCH:
154.04 – 154.23 Mb
Chr X:
75.17 – 75.38 Mb
PubMed search [1] [2]

Factor VIII (FVIII) is an essential blood-clotting protein, also known as anti-hemophilic factor (AHF). In humans, factor VIII is encoded by the F8 gene.[1][2] Defects in this gene results in hemophilia A, a recessive X-linked coagulation disorder.[3] Factor VIII is produced in liver sinusoidal cells and endothelial cells outside of the liver throughout the body. This protein circulates in the bloodstream in an inactive form, bound to another molecule called von Willebrand factor, until an injury that damages blood vessels occurs.[4] In response to injury, coagulation factor VIII is activated and separates from von Willebrand factor. The active protein (sometimes written as coagulation factor VIIIa) interacts with another coagulation factor called factor IX. This interaction sets off a chain of additional chemical reactions that form a blood clot.[4]

Factor VIII participates in blood coagulation; it is a cofactor for factor IXa which, in the presence of Ca2+ 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.[5]

People with high levels of factor VIII are at increased risk for deep vein thrombosis and pulmonary embolism.[6]