Faktor VIII

F8
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	1CFG, 1D7P, 1IQD, 2R7E, 3CDZ, 3HNB, 3HNY, 3HOB, 4BDV, 1FAC, 3J2Q, 3J2S, 4KI5, 4PT6, 4XZU
Identifikatori
Aliasi	F8
Vanjski ID-jevi	OMIM: 300841 MGI: 88383 HomoloGene: 49153 GeneCards: F8
Lokacija gena (čovjek)
Hrom.	Hromosom X
Kraj	155,026,940 bp
Lokacija gena (miš)
Hrom.	Hromosom X (miš)
Kraj	74,426,221 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• vezivanje iona metala; • GO:0001948, GO:0016582 vezivanje za proteine; • oxidoreductase activity; • copper ion binding;
Ćelijska komponenta	• endoplasmic reticulum lumen; • ćelijska membrana; • extracellular region; • COPII-coated ER to Golgi transport vesicle; • endoplasmic reticulum-Golgi intermediate compartment membrane; • platelet alpha granule lumen; • Golđijeva membrana; • Vanćelijsko;
Biološki proces	• Hemostaza; • platelet degranulation; • Koagulacija (krv); • endoplasmic reticulum to Golgi vesicle-mediated transport; • COPII vesicle coating; • acute-phase response; • blood coagulation, intrinsic pathway; • platelet activation;
	Izvori:Amigo / QuickGO
Ortolozi
	2157
	14069
	ENSG00000185010
	ENSMUSG00000031196
	P00451
	Q06194
	NM_000132; NM_019863
	NM_001161373; NM_001161374; NM_007977
	NP_000123; NP_063916
	NP_001154845; NP_001154846; NP_032003
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Faktor VIII (FVIII) je esencijalni protein zgrušavanja krvi također poznat kao antihemofilni faktor (AHF). Kod ljudi faktor VIII kodiran je genom '"F8'".^[5]^[6] Defekti ovog gena rezultiraju hemofilijom A, recesivnim X-vezanim poremećajem koagulacije.^[7] Faktor VIII proizvodi se u sinusoidnim ćelijama jetre i endotelnim ćelijama izvan jetre u cijelom tijelu. Ovaj protein cirkuliše u krvotoku u neaktivnom obliku, vezan za drugu molekulu zvanu von Willebrandov faktor, sve dok ne dođe do ozljede koja oštećuje krvne sudove.^[8] Kao odgovor na povredu, faktor koagulacije VIII se aktivira i odvaja od von Willebrand faktora. Aktivni protein (ponekad napisan kao faktor koagulacije VIIIa) stupa u interakciju sa drugim faktorom koagulacije koji se zove faktor IX. Ova interakcija pokreće lanac dodatnih hemijskih reakcija koje stvaraju krvni ugrušak.^[8]

Faktor VIII učestvuje u koagulaciji krvi; to je kofaktor za faktor IXa, koji, u prisustvu Ca²⁺ i fosfolipida, formira kompleks koji pretvara faktor X u aktivirani oblik Xa. Gen faktor VIII proizvodi dva alternativno prerađena transkripta. Varijanta transkripta 1 kodira veliki glikoprotein, izoformu a, koji cirkuliše u plazmi i povezuje se sa von Willebrand faktorom u nekovalentnom kompleksu. Ovaj protein podliježe višestrukim događajima cijepanja. Varijanta transkripta 2 kodira navodni mali protein, izoformu b, koji se prvenstveno sastoji od domena za vezivanje fosfolipida faktora VIIIc. Ovaj domen vezivanja je neophodan za aktivnost koagulacije.^[9]

Ljudi sa visokim nivoom faktora VIII su pod povećanim rizikom od duboke venske tromboze i plućne embolije.^[10] Bakar je neophodan kofaktor za faktor VIII i poznato je da nedostatak bakra povećava aktivnost faktora VIII.^[11]

Genetika

Kod ljudi, gen F8 se nalazi na hromosomu X na poziciji q28.

Faktor VIII su prvi okarakterisali 1984. naučnici iz Genentech-a.^[12] Gen za faktor VIII nalazi se na hromosomu X (Xq28). Gen za faktor VIII predstavlja zanimljivu primarnu strukturu, budući da je drugi gen (F8A1) ugrađen u jedan od njegovih introna.^[13]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca proteina je 2 351 aminokiselina, a molekulska težina — 267 009 Da^[14].

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MQIELSTCFF	LCLLRFCFSA	TRRYYLGAVE	LSWDYMQSDL	GELPVDARFP
PRVPKSFPFN	TSVVYKKTLF	VEFTDHLFNI	AKPRPPWMGL	LGPTIQAEVY
DTVVITLKNM	ASHPVSLHAV	GVSYWKASEG	AEYDDQTSQR	EKEDDKVFPG
GSHTYVWQVL	KENGPMASDP	LCLTYSYLSH	VDLVKDLNSG	LIGALLVCRE
GSLAKEKTQT	LHKFILLFAV	FDEGKSWHSE	TKNSLMQDRD	AASARAWPKM
HTVNGYVNRS	LPGLIGCHRK	SVYWHVIGMG	TTPEVHSIFL	EGHTFLVRNH
RQASLEISPI	TFLTAQTLLM	DLGQFLLFCH	ISSHQHDGME	AYVKVDSCPE
EPQLRMKNNE	EAEDYDDDLT	DSEMDVVRFD	DDNSPSFIQI	RSVAKKHPKT
WVHYIAAEEE	DWDYAPLVLA	PDDRSYKSQY	LNNGPQRIGR	KYKKVRFMAY
TDETFKTREA	IQHESGILGP	LLYGEVGDTL	LIIFKNQASR	PYNIYPHGIT
DVRPLYSRRL	PKGVKHLKDF	PILPGEIFKY	KWTVTVEDGP	TKSDPRCLTR
YYSSFVNMER	DLASGLIGPL	LICYKESVDQ	RGNQIMSDKR	NVILFSVFDE
NRSWYLTENI	QRFLPNPAGV	QLEDPEFQAS	NIMHSINGYV	FDSLQLSVCL
HEVAYWYILS	IGAQTDFLSV	FFSGYTFKHK	MVYEDTLTLF	PFSGETVFMS
MENPGLWILG	CHNSDFRNRG	MTALLKVSSC	DKNTGDYYED	SYEDISAYLL
SKNNAIEPRS	FSQNSRHPST	RQKQFNATTI	PENDIEKTDP	WFAHRTPMPK
IQNVSSSDLL	MLLRQSPTPH	GLSLSDLQEA	KYETFSDDPS	PGAIDSNNSL
SEMTHFRPQL	HHSGDMVFTP	ESGLQLRLNE	KLGTTAATEL	KKLDFKVSST
SNNLISTIPS	DNLAAGTDNT	SSLGPPSMPV	HYDSQLDTTL	FGKKSSPLTE
SGGPLSLSEE	NNDSKLLESG	LMNSQESSWG	KNVSSTESGR	LFKGKRAHGP
ALLTKDNALF	KVSISLLKTN	KTSNNSATNR	KTHIDGPSLL	IENSPSVWQN
ILESDTEFKK	VTPLIHDRML	MDKNATALRL	NHMSNKTTSS	KNMEMVQQKK
EGPIPPDAQN	PDMSFFKMLF	LPESARWIQR	THGKNSLNSG	QGPSPKQLVS
LGPEKSVEGQ	NFLSEKNKVV	VGKGEFTKDV	GLKEMVFPSS	RNLFLTNLDN
LHENNTHNQE	KKIQEEIEKK	ETLIQENVVL	PQIHTVTGTK	NFMKNLFLLS
TRQNVEGSYD	GAYAPVLQDF	RSLNDSTNRT	KKHTAHFSKK	GEEENLEGLG
NQTKQIVEKY	ACTTRISPNT	SQQNFVTQRS	KRALKQFRLP	LEETELEKRI
IVDDTSTQWS	KNMKHLTPST	LTQIDYNEKE	KGAITQSPLS	DCLTRSHSIP
QANRSPLPIA	KVSSFPSIRP	IYLTRVLFQD	NSSHLPAASY	RKKDSGVQES
SHFLQGAKKN	NLSLAILTLE	MTGDQREVGS	LGTSATNSVT	YKKVENTVLP
KPDLPKTSGK	VELLPKVHIY	QKDLFPTETS	NGSPGHLDLV	EGSLLQGTEG
AIKWNEANRP	GKVPFLRVAT	ESSAKTPSKL	LDPLAWDNHY	GTQIPKEEWK
SQEKSPEKTA	FKKKDTILSL	NACESNHAIA	AINEGQNKPE	IEVTWAKQGR
TERLCSQNPP	VLKRHQREIT	RTTLQSDQEE	IDYDDTISVE	MKKEDFDIYD
EDENQSPRSF	QKKTRHYFIA	AVERLWDYGM	SSSPHVLRNR	AQSGSVPQFK
KVVFQEFTDG	SFTQPLYRGE	LNEHLGLLGP	YIRAEVEDNI	MVTFRNQASR
PYSFYSSLIS	YEEDQRQGAE	PRKNFVKPNE	TKTYFWKVQH	HMAPTKDEFD
CKAWAYFSDV	DLEKDVHSGL	IGPLLVCHTN	TLNPAHGRQV	TVQEFALFFT
IFDETKSWYF	TENMERNCRA	PCNIQMEDPT	FKENYRFHAI	NGYIMDTLPG
LVMAQDQRIR	WYLLSMGSNE	NIHSIHFSGH	VFTVRKKEEY	KMALYNLYPG
VFETVEMLPS	KAGIWRVECL	IGEHLHAGMS	TLFLVYSNKC	QTPLGMASGH
IRDFQITASG	QYGQWAPKLA	RLHYSGSINA	WSTKEPFSWI	KVDLLAPMII
HGIKTQGARQ	KFSSLYISQF	IIMYSLDGKK	WQTYRGNSTG	TLMVFFGNVD
SSGIKHNIFN	PPIIARYIRL	HPTHYSIRST	LRMELMGCDL	NSCSMPLGME
SKAISDAQIT	ASSYFTNMFA	TWSPSKARLH	LQGRSNAWRP	QVNNPKEWLQ
VDFQKTMKVT	GVTTQGVKSL	LTSMYVKEFL	ISSSQDGHQW	TLFFQNGKVK
VFQGNQDSFT	PVVNSLDPPL	LTRYLRIHPQ	SWVHQIALRM	EVLGCEAQDL
Y

Struktura

Protein faktora VIII sastoji se od šest domena: A1-A2-B-A3-C1-C2, i homologna sa faktorom V.

A domeni su homologni sa A domenima proteina koji vezuje bakarni ceruloplazmin.^[15] C domen pripada porodici domena koji se vezuje za fosfolipide, a domen 2 posreduje u vezivanju membrane.^[16]

Aktivacija faktora VIII u faktor VIIIa vrši se cijepanjem i oslobađanjem B domena. Protein je sada podijeljen na teški lanac, koji se sastoji od A1-A2 domena, i lahki lanac, koji se sastoji od A3-C1-C2 domena. Oboje formiraju nekovalentno kompleks na način ovisan o kalciju. Ovaj kompleks je prokoagulantni faktor VIIIa.^[17]

Fiziologija

FVIII je glikoprotein prokofaktor. Iako je primarno mjesto oslobađanja kod ljudi dvosmisleno, sintetizira se i otpušta u krvotok putem vaskularnih, glomerulskih i tubularnih endotela i sinusoidnih ćelija jetre.^[18] Hemofilija A je korigirana transplantacijom.^[19] Transplantacija hepatocita je bila neefikasna, ali su endotelne ćelije jetre bile efikasne.^[19]

U krvi uglavnom cirkuliše u stabilnim Nekovalentnom kompleksu sa von Willebrandovim faktorom. Nakon aktivacije pomoću trombin a (faktor IIa), on se odvaja od kompleksa da bi stupio u interakciju sa faktorom IXa u kaskadi koagulacije. On je kofaktor za faktor IXa u aktivaciji faktora, koji, zauzvrat, sa svojim kofaktorom faktorom Va, aktivira više trombina. Trombin cijepa fibrinogen u fibrin koji se polimerizira i umrežava (koristeći faktor XIII) u krvni ugrušak.

Protein faktora VIII ima poluživot od 12 sati u krvotoku kada ga stabilizira von Willebrandov faktor.^[20]

Više nije zaštićen vWF, aktivirani FVIII je proteolitski inaktiviran u tom procesu (najčešće aktiviranim proteinom C i faktorom IXa) i brzo se uklanja iz krvotoka.

Faktor VIII nije pod uticajem bolesti jetre. U stvari, nivoi su obično povišeni u takvim slučajevima.^[21]^[22]

Medicinska upotreba

FVIII koncentrovan iz darovane krvne plazme, ili alternativno rekombinantni FVIIa se može dati hemofiličarima radi obnavljanja homeostaze.

Formiranje antitijela na faktor VIII takođe može biti velika briga za pacijente koji primaju terapiju protiv krvarenja. Učestalost ovih inhibitora zavisi od različitih faktora, uključujući sam proizvod faktora VIII.^[23]

Meta imunobojenja

Antigen povezan s faktorom VIII koristi se kao meta za imunohistohemiju, gdje se endotelne ćelije, megakariociti, trombociti i mastociti normalno boje pozitivno.^[24]

Skandal kontaminacije

U 1980-im, neke farmaceutske kompanije kao što su Baxter International i Bayer izazvale su kontroverzu nastavljajući prodaju kontaminiranog faktora VIII nakon što su bile dostupne nove termički obrađene verzije.^[25] Pod pritiskom FDA, nezagrijani proizvod je povučen sa tržišta SAD-a, ali je prodan u azijske, latinoameričke i neke evropske zemlje. Proizvod je bio uprljan HIV-om, o čemu su razgovarali Bayer i američka Uprava za hranu i lijekove (FDA).^[25]

Početkom 1990-ih, farmaceutske kompanije počele su proizvoditi rekombinantne proizvode sintetiziranih faktora, koji sada sprječavaju gotovo sve oblike prijenosa bolesti tokom zamjenske terapije.

Historija

Faktor VIII je prvi put otkriven 1937. godine, ali je tek 1979. njegovo pročišćavanje izveli Edward Tuddenham, Frances Rotblat i saradnici, što je dovelo do molekulske identifikacije proteina.^[26]^[27]

Također pogledajte

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000185010 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000031196 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Toole JJ, Knopf JL, Wozney JM, Sultzman LA, Buecker JL, Pittman DD, Kaufman RJ, Brown E, Shoemaker C, Orr EC (1984). "Molecular cloning of a cDNA encoding human antihaemophilic factor". Nature. 312 (5992): 342–47. Bibcode:1984Natur.312..342T. doi:10.1038/312342a0. PMID 6438528. S2CID 4313575.
^ Truett MA, Blacher R, Burke RL, Caput D, Chu C, Dina D, Hartog K, Kuo CH, Masiarz FR, Merryweather JP (oktobar 1985). "Characterization of the polypeptide composition of human factor VIII:C and the nucleotide sequence and expression of the human kidney cDNA". DNA. 4 (5): 333–49. doi:10.1089/dna.1985.4.333. PMID 3935400.
^ Antonarakis SE (juli 1995). "Molecular genetics of coagulation factor VIII gene and hemophilia A". Thrombosis and Haemostasis. 74 (1): 322–28. doi:10.1055/s-0038-1642697. PMID 8578479.
^ ^a ^b "NIH: F8 – coagulation factor VIII". National Institutes of Health.
^ "Entrez Gene: F8 coagulation factor VIII, procoagulant component (hemophilia A)".
^ Jenkins PV, Rawley O, Smith OP, O'Donnell JS (juni 2012). "Elevated factor VIII levels and risk of venous thrombosis". British Journal of Haematology. 157 (6): 653–63. doi:10.1111/j.1365-2141.2012.09134.x. PMID 22530883.
^ Milne DB, Nielsen FH (mart 1996). "Effects of a diet low in copper on copper-status indicators in postmenopausal women". The American Journal of Clinical Nutrition. 63 (3): 358–64. doi:10.1093/ajcn/63.3.358. PMID 8602593.
^ Gitschier J, Wood WI, Goralka TM, Wion KL, Chen EY, Eaton DH, Vehar GA, Capon DJ, Lawn RM (novembar 1984). "Characterization of the human factor VIII gene". Nature. 312 (5992): 326–30. Bibcode:1984Natur.312..326G. doi:10.1038/312326a0. PMID 6438525. S2CID 4358041.
^ Levinson B, Kenwrick S, Lakich D, Hammonds G, Gitschier J (maj 1990). "A transcribed gene in an intron of the human factor VIII gene". Genomics. 7 (1): 1–11. doi:10.1016/0888-7543(90)90512-S. PMID 2110545.
^ "UniProt, P00451" (jezik: engleski). Arhivirano s originala, 6 march 2017. Pristupljeno march 12, 2017. Provjerite vrijednost datuma u parametru: |access-date= i |archive-date= (pomoć)
^ Villoutreix BO, Dahlbäck B (juni 1998). "Structural investigation of the A domains of human blood coagulation factor V by molecular modeling". Protein Science. 7 (6): 1317–25. doi:10.1002/pro.5560070607. PMC 2144041. PMID 9655335.
^ Macedo-Ribeiro S, Bode W, Huber R, Quinn-Allen MA, Kim SW, Ortel TL, Bourenkov GP, Bartunik HD, Stubbs MT, Kane WH, Fuentes-Prior P (novembar 1999). "Crystal structures of the membrane-binding C2 domain of human coagulation factor V". Nature. 402 (6760): 434–39. Bibcode:1999Natur.402..434M. doi:10.1038/46594. PMID 10586886. S2CID 4393638.
^ Thorelli E, Kaufman RJ, Dahlbäck B (juni 1998). "The C-terminal region of the factor V B-domain is crucial for the anticoagulant activity of factor V". The Journal of Biological Chemistry. 273 (26): 16140–45. doi:10.1074/jbc.273.26.16140. PMID 9632668.
^ Kumar V, Abbas A, Aster J (2005). Robbins and Cotran Pathologic Basis of Disease (9th izd.). Pennsylvania: Elsevier. str. 655. ISBN 978-0-8089-2450-0.
^ ^a ^b Kaushansky K, Lichtman M, Beutler E, Kipps T, Prchal J, Seligsohn U (2010). Williams Hematology (8th izd.). McGraw-Hill. ISBN 978-0-07-162151-9.
^ Fischer, Kathelijn; Pendu, Ronan; van Schooten, Carina J.; van Dijk, Karin; Denis, Cécile V.; van den Berg, H. Marijke; Lenting, Peter J. (25. 8. 2009). "Models for Prediction of Factor VIII Half-Life in Severe Haemophiliacs: Distinct Approaches for Blood Group O and Non-O Patients". PLOS ONE. 4 (8): e6745. Bibcode:2009PLoSO...4.6745F. doi:10.1371/journal.pone.0006745. ISSN 1932-6203. PMC 2727052. PMID 19707594.
^ Hollestelle MJ, Geertzen HG, Straatsburg IH, van Gulik TM, van Mourik JA (februar 2004). "Factor VIII expression in liver disease". Thrombosis and Haemostasis. 91 (2): 267–75. doi:10.1160/th03-05-0310. PMID 14961153.
^ Rubin R, Leopold L (1998). Hematologic Pathophysiology. Madison, Conn: Fence Creek Publishing. ISBN 1-889325-04-X.
^ Lozier J (2004). "Overview of Factor VIII Inhibitors". CMEonHemophilia.com. Arhivirano s originala, 16. 12. 2008. Pristupljeno 7. 1. 2009.
^ Nat Pernick, M.D. "Stains & CD markers - Factor VIII related antigen". Pathology Outlines. Topic Completed: 1 July 2012. Minor changes: 25 June 2021
^ ^a ^b Bogdanich W, Koli E (22. 5. 2003). "2 Paths of Bayer Drug in 80's: Riskier One Steered Overseas". The New York Times: A1, C5. PMID 12812170. Pristupljeno 7. 1. 2009.
^ Tuddenham EG, Trabold NC, Collins JA, Hoyer LW (1979). "The properties of factor VIII coagulant activity prepared by immunoadsorbent chromatography". J Lab Clin Med. 93 (1): 40–53. PMID 366050.CS1 održavanje: više imena: authors list (link)
^ "Frances Rotblat obituary". The Times. 12. 6. 2021. Pristupljeno 12. 6. 2021.

Dopunska literatura

Gitschier J (1991). "The molecular basis of hemophilia A". Annals of the New York Academy of Sciences. 614 (1 Process in Va): 89–96. Bibcode:1991NYASA.614...89G. doi:10.1111/j.1749-6632.1991.tb43694.x. PMID 1902642. S2CID 26493612.
White GC, Shoemaker CB (januar 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". Human Mutation. 5 (1): 1–22. doi:10.1002/humu.1380050102. PMID 7728145. S2CID 2346510.
Lenting PJ, van Mourik JA, Mertens K (decembar 1998). "The life cycle of coagulation factor VIII in view of its structure and function". Blood. 92 (11): 3983–96. doi:10.1182/blood.V92.11.3983. PMID 9834200.
Saenko EL, Ananyeva N, Kouiavskaia D, Schwinn H, Josic D, Shima M, Hauser CA, Pipe S (august 2002). "Molecular defects in coagulation Factor VIII and their impact on Factor VIII function" (PDF). Vox Sanguinis. 83 (2): 89–96. doi:10.1046/j.1423-0410.2002.00183.x. hdl:2027.42/74861. PMID 12201837.
Lollar P (august 2002). "Molecular characterization of the immune response to factor VIII". Vox Sanguinis. 83. 83 Suppl 1: 403–08. doi:10.1111/j.1423-0410.2002.tb05342.x. PMID 12617176. S2CID 26050729.
Fay PJ (mart 2004). "Activation of factor VIII and mechanisms of cofactor action". Blood Reviews. 18 (1): 1–15. doi:10.1016/S0268-960X(03)00025-0. PMID 14684146.
Lavigne-Lissalde G, Schved JF, Granier C, Villard S (oktobar 2005). "Anti-factor VIII antibodies: a 2005 update". Thrombosis and Haemostasis. 94 (4): 760–69. doi:10.1160/TH05-02-0118. PMID 16270627.
Fang H, Wang L, Wang H (2007). "The protein structure and effect of factor VIII". Thrombosis Research. 119 (1): 1–13. doi:10.1016/j.thromres.2005.12.015. PMID 16487577.

Vanjski linkovi

GeneReviews/NCBI/NIH/UW entry on Hemophilia A
The Coagulation Factor VIII Protein
Factor VIII na US National Library of Medicine Medical Subject Headings (MeSH)
P00451

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000185010 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000031196 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid6438528-5] Toole JJ, Knopf JL, Wozney JM, Sultzman LA, Buecker JL, Pittman DD, Kaufman RJ, Brown E, Shoemaker C, Orr EC (1984). "Molecular cloning of a cDNA encoding human antihaemophilic factor". Nature. 312 (5992): 342–47. Bibcode:1984Natur.312..342T. doi:10.1038/312342a0. PMID 6438528. S2CID 4313575.

[pmid3935400-6] Truett MA, Blacher R, Burke RL, Caput D, Chu C, Dina D, Hartog K, Kuo CH, Masiarz FR, Merryweather JP (oktobar 1985). "Characterization of the polypeptide composition of human factor VIII:C and the nucleotide sequence and expression of the human kidney cDNA". DNA. 4 (5): 333–49. doi:10.1089/dna.1985.4.333. PMID 3935400.

[pmid8578479-7] Antonarakis SE (juli 1995). "Molecular genetics of coagulation factor VIII gene and hemophilia A". Thrombosis and Haemostasis. 74 (1): 322–28. doi:10.1055/s-0038-1642697. PMID 8578479.

[NIH:_F8_-_coagulation_factor_VIII-8] "NIH: F8 – coagulation factor VIII". National Institutes of Health.

[entrez-9] "Entrez Gene: F8 coagulation factor VIII, procoagulant component (hemophilia A)".

[Jenkins-10] Jenkins PV, Rawley O, Smith OP, O'Donnell JS (juni 2012). "Elevated factor VIII levels and risk of venous thrombosis". British Journal of Haematology. 157 (6): 653–63. doi:10.1111/j.1365-2141.2012.09134.x. PMID 22530883.

[Milne-11] Milne DB, Nielsen FH (mart 1996). "Effects of a diet low in copper on copper-status indicators in postmenopausal women". The American Journal of Clinical Nutrition. 63 (3): 358–64. doi:10.1093/ajcn/63.3.358. PMID 8602593.

[12] Gitschier J, Wood WI, Goralka TM, Wion KL, Chen EY, Eaton DH, Vehar GA, Capon DJ, Lawn RM (novembar 1984). "Characterization of the human factor VIII gene". Nature. 312 (5992): 326–30. Bibcode:1984Natur.312..326G. doi:10.1038/312326a0. PMID 6438525. S2CID 4358041.

[13] Levinson B, Kenwrick S, Lakich D, Hammonds G, Gitschier J (maj 1990). "A transcribed gene in an intron of the human factor VIII gene". Genomics. 7 (1): 1–11. doi:10.1016/0888-7543(90)90512-S. PMID 2110545.

[UniProt-14] "UniProt, P00451" (jezik: engleski). Arhivirano s originala, 6 march 2017. Pristupljeno march 12, 2017. Provjerite vrijednost datuma u parametru: |access-date= i |archive-date= (pomoć)

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