antihemophilic factor

抗血友病因子

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

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/29 14:36:47」(JST)

wiki en

[Wiki en表示]

For the documentary, see Factor 8: The Arkansas Prison Blood Scandal

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, 3J2Q, 3J2S, 4BDV, 4KI5, 4PT6
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 • blood coagulation • blood coagulation, intrinsic pathway • platelet activation • oxidation-reduction process 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 X: 154.84 – 155.03 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 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.

People with high levels of factor VIII are at increased risk for deep vein thrombosis and pulmonary embolism. Copper is a required cofactor for factor VIII and copper deficiency is known to increase levels of factor VIII.

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

• Ralph Kekwick
• Ryan White
• Edward Tuddenham
• Edward Shanbrom

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.  CS1 maint: Explicit use of et al. (link)
• Lollar P (2003). "Molecular characterization of the immune response to factor VIII". Vox Sang. 83. Suppl 1: 403–8. doi:10.1111/j.1423-0410.2002.tb05342.x. 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

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 血友病患者における第VIIIおよび第IX因子阻害物質 factor viii and factor ix inhibitors in patients with hemophilia
• 2. 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
• 3. 静脈血栓症の原因の概要 overview of the causes of venous thrombosis
• 4. Factor VIII human plasma-derived and recombinant products: Drug formulations
• 5. 血友病の治療 treatment of hemophilia

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

• 現代医学の焦点(304)血友病 今昔

• 日本臨床 66(3), 591-599, 2008-03
• NAID 40015862617

• 幼児に生じた下顎骨血友病性偽腫ようのｌ例

• 日本口腔科学会雑誌 46(4), 414-418, 1997
• NAID 130004114366

• 腹腔内出血を伴った新生児血友病 A の1例

• 日本小児外科学会雑誌 32(1), 43-47, 1996-02-20
• NAID 110002107479

Related Links

• Factor VIII - Wikipedia, the free encyclopedia

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 ...

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★リンクテーブル★

リンク元	「血液凝固因子」「blood coagulation factor VIII」「coagulation factor VIII」
関連記事	「fact」「factor」

「血液凝固因子」

　　[★]

英

coagulation factor (Z), clotting factor, blood coagulation factor, blood coagulation factors

関

ビタミンK

血液凝固因子

• 第I因子
• 第II因子
• 第III因子
• 第IV因子
• 第V因子
• 第VII因子
• 第VIII因子
• 第IX因子
• 第X因子
• 第XI因子
• 第XII因子
• 第XIII因子

表

• PT.261

型	名称	同義語	分子量 (kDa)	血漿中濃度 (μg/ml)	半減期 (day)
内因系のプロ酵素	XII	Hageman因子	80	29	2
	プレカリクレイン	Fletcher因子	88	45
	XI	PTA	160	4	2.5
ビタミンK依存	VII	proconvertin	50	0.5	0.2
凝固プロ酵素	IX	Christmas因子	57	4	1
	X	Stuart因子	57	8	1.5
	II	プロトロンビン	70	150	3
補助因子	III	組織因子		0
	血小板ホスホリピド
	高分子量キニノゲン		120	70
	V	proaccelerin	330	7	1.5
	VIII	抗血友病因子			0.5
フィブリン堆積因子	I	フィブリノゲン	340	2500	4.5
	XIII	フィブリン安定因子	320	8	7
抑制物質	アンチトロンビンIII		58	150	2.5

• 標準血液病学 p.217

15種類ある

凝固因子	慣用語・同義語	ビタミンK依存	血液中半減期(hr)	産生器官	染色体座乗部位
I	fibrinogen		100-150	肝臓	4q26
II	prothronbin	○	50-80	肝臓	11p141-q12
III	tissue thromboplastin			体の各組織	1pter-p21
IV	calcium ion			肝臓
V	labile factor/proaccelerin		24	肝臓	1q21-q25
VII	stable factor/proconvertin	○	6	肝臓	13q34
VIII	antihemophilic factor		12	細網系?	xq28
IX	Christmas factor	○	24	肝臓	xq26.3-q27.2
X	Stuart factor	○	25-60	肝臓	13q34
XI	plasma thromboplastin antecedent		40-80	肝臓	4q35
XII	Hageman factor		50-70	肝臓	5q33-qter
XIII	fibrin stabilizing factor		150	肝臓	6p24-p21.3
prekallikrein	Fletcher factor		35	肝臓	4q35
hight molecular weight kininogen	Fitzgerold factor		150	肝臓	3q26-qter
von Willebrand factor			24	血管内皮 血小板 糸球体	12pter-p12

産生部位

• ほとんどが肝臓
• 例外：

• 第III因子(F III)：組織トロンボプラスチン：組織
• 第VIII因子(F VIII)：組織トロンボプラスチン：細網組織？

臨床関連

• ビタミンK欠乏
• 妊娠により第XI因子、第XIII因子を除き、血液凝固因子の濃度が上昇する

-凝固因子

「blood coagulation factor VIII」

　　[★]

• 血液凝固第VIII因子

関

antihemophilic factor、coagulation factor VIII、factor VIII

「coagulation factor VIII」

　　[★]

• 凝固第VIII因子

関

antihemophilic factor、blood coagulation factor VIII、factor VIII

「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