factor VIII

第VIII因子

WordNet

1. be a contributing factor; "make things factor into a companys profitability"
2. any of the numbers (or symbols) that form a product when multiplied together
3. an independent variable in statistics
4. anything that contributes causally to a result; "a number of factors determined the outcome"
5. consider as relevant when making a decision; "You must factor in the recent developments" (同)factor in, factor out
6. resolve into factors; "a quantum computer can factor the number 15" (同)factor in, factor out
7. an event known to have happened or something known to have existed; "your fears have no basis in fact"; "how much of the story is fact and how much fiction is hard to tell"
8. a concept whose truth can be proved; "scientific hypotheses are not facts"
9. a piece of information about circumstances that exist or events that have occurred; "first you must collect all the facts of the case"
10. a statement or assertion of verified information about something that is the case or has happened; "he supported his argument with an impressive array of facts"

PrepTutorEJDIC

1. (…の)『要因』,(…を生み出す)要素《+『in』+『名』(do『ing』)》 / 囲数,約数 / 代理人,《おもに英》仲買人 / =factorize
2. 〈C〉『事実』,実際にある(あった)事 / 〈U〉真相,真実(truth) / 《the~》(法律用語で)犯行
3. Virgin Islands

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/05/30 20:28:28」(JST)

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[Wiki en表示]

Coagulation factor VIII, procoagulant component
PDB rendering based on 2R7E.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1CFG, 1D7P, 1FAC, 1IQD, 2R7E, 3CDZ, 3HNB, 3HNY, 3HOB, 4BDV
Identifiers
Symbols	F8; AHF; DXS1253E; F8B; F8C; FVIII; HEMA
External IDs	OMIM: 300841 MGI: 88383 HomoloGene: 49153 ChEMBL: 3143 GeneCards: F8 Gene
Gene Ontology Molecular function • copper ion binding • protein binding • oxidoreductase activity Cellular component • extracellular region • extracellular space • plasma membrane • platelet alpha granule lumen Biological process • platelet degranulation • acute-phase response • cell adhesion • blood coagulation • blood coagulation, intrinsic pathway • platelet activation Sources: Amigo / QuickGO
RNA expression pattern
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. Defects in this gene results in hemophilia A, a recessive X-linked coagulation disorder. 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. 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.

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.

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

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.

Physiology

FVIII is a glycoprotein procofactor. Although the primary site of release in humans is ambiguous, it is synthesized and released into the bloodstream by the vascular, glomerular, and tubular endothelium, and the sinusoidal cells of the liver. Hemophilia A has been corrected by liver transplantation. Transplanting hepatocytes was ineffective, but liver endothelial cells were effective.

In the blood, it mainly circulates in a stable noncovalent complex with von Willebrand factor. 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 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 not affected by liver disease. In fact, levels usually are elevated in such instances.

Therapeutic use

FVIII concentrated from donated blood plasma (Aafact or Alphanate, Monoclate-P®), 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.

Contamination scandal

Main article: Contaminated haemophilia blood products

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. Under FDA pressure, unheated product was pulled from US markets, but was sold to Asian, Latin American, and some European countries. The product was tainted with HIV, a concern that had been discussed by Bayer and the U.S. Food and Drug Administration (FDA).

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.

See also

• Prof Ralph Kekwick FRS
• Ryan White
• Professor Edward Tuddenham

References

Further reading

• Gitschier J (1991). "The molecular basis of hemophilia A". Ann. N. Y. Acad. Sci. 614 (1 Process in Va): 89–96. doi:10.1111/j.1749-6632.1991.tb43694.x. PMID 1902642. 
• White GC, Shoemaker CB (1989). "Factor VIII gene and hemophilia A". Blood 73 (1): 1–12. PMID 2491949. 
• Antonarakis SE, Kazazian HH, Tuddenham EG (1995). "Molecular etiology of factor VIII deficiency in hemophilia A". Hum. Mutat. 5 (1): 1–22. doi:10.1002/humu.1380050102. PMID 7728145. 
• Lenting PJ, van Mourik JA, Mertens K (1999). "The life cycle of coagulation factor VIII in view of its structure and function". Blood 92 (11): 3983–96. PMID 9834200. 
• Saenko EL, Ananyeva N, Kouiavskaia D, et al. (2003). "Molecular defects in coagulation Factor VIII and their impact on Factor VIII function". Vox Sang. 83 (2): 89–96. doi:10.1046/j.1423-0410.2002.00183.x. PMID 12201837. 
• Lollar P (2003). "Molecular characterization of the immune response to factor VIII". Vox Sang. 83. Suppl 1: 403–8. PMID 12617176. 
• Fay PJ (2004). "Activation of factor VIII and mechanisms of cofactor action". Blood Rev. 18 (1): 1–15. doi:10.1016/S0268-960X(03)00025-0. PMID 14684146. 
• Lavigne-Lissalde G, Schved JF, Granier C, Villard S (2005). "Anti-factor VIII antibodies: a 2005 update". Thromb. Haemost. 94 (4): 760–9. doi:10.1160/TH05-02-0118. PMID 16270627. 
• Fang H, Wang L, Wang H (2007). "The protein structure and effect of factor VIII". Thromb. Res. 119 (1): 1–13. doi:10.1016/j.thromres.2005.12.015. PMID 16487577. 

External links

• GeneReviews/NCBI/NIH/UW entry on Hemophilia A
• The Coagulation Factor VIII Protein
• Factor VIII at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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• 1. 血友病A・血友病B：予防を含めた日常的なマネージメントhemophilia a and b routine management including prophylaxis [show details]
  …following strategies have been used for half-life extension for factor VIII: Factor VIII-Fc fusion – A recombinant product composed of factor VIII fused with a monomeric human immunoglobulin (IgG1) Fc domain …
• 2. 血友病A・血友病Bに伴う出血の治療と周術期マネージメントtreatment of bleeding and perioperative management in hemophilia a and b [show details]
  … anti-porcine factor VIII antibodies is available; subsequent dosing is guided by standard factor VIII activity levels. Monitoring factor VIII levels is essential. A plasma-derived porcine factor VIII (Hyate-C) …
• 3. 第VIII因子および第IX因子の生物学と正常な機能biology and normal function of factor viii and factor ix [show details]
  … so that circulating plasma factor VIII is a heterodimer. Factor VIII circulates in plasma in a noncovalent complex with von Willebrand factor. Cleavage of plasma factor VIII by thrombin or factor Xa at …
• 4. 血友病患者に生じる慢性合併症と加齢に伴い生じる併存症chronic complications and age related comorbidities in people with hemophilia [show details]
  … Hemophilia A (factor VIII [factor 8] deficiency) and hemophilia B (factor IX [factor 9] deficiency) are X-linked inherited coagulation factor deficiencies. The availability of factor replacement products …
• 5. von Willebrand病の治療treatment of von willebrand disease [show details]
  …mutations occur within the binding site for factor VIII and cause decreased binding to factor VIII, which is then catabolized more quickly. As a result, factor VIII levels are usually 5 to 15 percent of normal …

English Journal

• Violating the theory of single gene-single disorder: inhibitor development in hemophilia.

• AlFadhli S1, Nizam R1.
• Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion.Indian J Hematol Blood Transfus.2015 Jun;31(2):162-8. doi: 10.1007/s12288-014-0473-2. Epub 2014 Nov 20.
• Hemophilia is clinically and genetically heterogeneous blood disorder with several known gene defects accounting for the diversity of disease phenotype and inhibitor production. Although increasing number of causative mutations have been reported, not much is known regarding the root cause of inhibi
• PMID 25825553

• Characterization of thymus atrophy in calves with subclinical BVD challenged with BHV-1.

• Romero-Palomo F1, Risalde MA1, Molina V1, Lauzi S2, Bautista MJ1, Gómez-Villamandos JC3.
• Veterinary microbiology.Vet Microbiol.2015 May 15;177(1-2):32-42. doi: 10.1016/j.vetmic.2015.02.018. Epub 2015 Feb 26.
• Since the thymus is a target organ for the bovine viral diarrhea virus (BVDV), our experiment aimed to understand its relationship with the immunosuppressive effect by studying the consequences of a previous infection with BVDV on the thymus of calves challenged with bovine herpesvirus 1.1 (BHV-1).
• PMID 25759294

• The acute effect of moderate intensity aquatic exercise on coagulation factors in haemophiliacs.

• Beltrame LG1, Abreu L, Almeida J, Boullosa DA.
• Clinical physiology and functional imaging.Clin Physiol Funct Imaging.2015 May;35(3):191-6. doi: 10.1111/cpf.12145. Epub 2014 Apr 10.
• The objective of this cross-sectional study was to analyse the acute effect of aquatic exercise on haemostasis in persons with haemophilia. Ten adult haemophiliacs (8 type A, 2 type B) familiarized with aquatic training performed a 20-min exercise session in a swimming pool at an intensity of ~70% m
• PMID 24720506

Japanese Journal

• Acute Myeloid Leukemia with Mastocytic and Megakaryocytic Differentiation in a Calf

• IKEHATA Tsutomu,WADA Yoshihiro,ISHIKAWA Yoshiharu,KADOTA Koichi
• Journal of Veterinary Medical Science 73(4), 467-470, 2011
• … Histochemical and immunohistochemical examination disclosed the presence of neoplastic cells either containing metachromatic and tryptase-positive granules or expressing factor VIII-related antigen. …
• NAID 130000444380

• 後天性凝固異常症の病態と治療 : 後天性血友病を中心に

• 嶋 緑倫
• 臨床血液 51(10), 211-218, 2010-10-30
• NAID 10026728459

Related Links

• F-免疫染色 協同病理

（Coagulation) Factor VIII related antigen ( F-VIII RA ) ( 別名：Von Willebrand factor：vWF ) F-VIII RA 血管 X400 第VIII因子関連抗原は省略して「第VIII因子」と呼ばれたりすることもあるが正確には第VIII凝固因子そのものではなく、その ...

• factor VIIIの意味 - 英和辞書 - goo辞書

factor VIIIとは。意味や和訳。《生化学》第VIII因子：血液凝固に必要なたんぱく質. - goo辞書は国語、英和、和英、中国語、百科事典等からまとめて探せる辞書検索サービスです。

Related Pictures

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★リンクテーブル★

リンク元	「第VIII因子」「coagulation factor VIII」
拡張検索	「factor VIII deficiency」「coagulation factor VIIIa」「blood coagulation factor VIII」「factor VIIIa」
関連記事	「fact」「factor」

「第VIII因子」

　　[★]

英

factor VIII, FVIII

同

血漿トロンボプラスチン因子 plasma thromboplastin factor PTF

抗血友病グロブリン antihemophilic globulin、抗血友病因子A antihemophilic factor A platelet cofactor I、抗血友病因子

商

(オクトコグアルファ)コージネイト

(ルリオクトコグアルファ)アドベイト

クロスエイト、コンコエイト、コンファクト

関

血液凝固因子、血友病

[show details]

第VIII因子 : 約 233,000 件
凝固第VIII因子 : 約 65,300 件
血液凝固第VIII因子 : 約 52,200 件

存在部位

• von Willebrand因子と結合
• 血小板のα顆粒の中

半減期

• 12 hr

• 第IX因子の半減期は24hrなので、血友病Aは血友病Bより短い間隔で第VIII因子を投与する必要がある。

産生組織

• 細網系?

肝以外で産生される凝固因子

• 第III因子(tissue factor)
• 第VIII因子
• von Willebrand factor

座乗染色体

• xq28

臨床関連

• 血友病A

「coagulation factor VIII」

　　[★]

• 凝固第VIII因子

関

antihemophilic factor、blood coagulation factor VIII、factor VIII

「factor VIII deficiency」

　　[★]

第VIII因子欠乏症、第VIII因子欠損症

関

haemophilia、hemophilia、hemophilia A

「coagulation factor VIIIa」

　　[★]

• 活性化凝固第VIII因子、活性化第VIII因子

関

activated factor VIII、factor VIIIa

「blood coagulation factor VIII」

　　[★]

• 血液凝固第VIII因子

関

antihemophilic factor、coagulation factor VIII、factor VIII

「factor VIIIa」

　　[★]

活性化第VIII因子

関

activated factor VIII、coagulation factor VIIIa

「fact」

　　[★]

• n.

• 事実、現状、実際、実態

関

actual、actually、in fact、in practice、indeed、practically

　 　 　 　 　

「factor」

　　[★]

• n.

• 因子、要因、要素、ファクター

関

element、elementary、factorial、parameter