FVIII

UK haemophilia centre directors organisation, Hay C.R.M., Ludlam C.A., Colvin B.T., Hill F.G.H., Preston F.E., Wasseem N., Bagnall R., Peake I.R., Berntorp E., Mauser Bunschoten E.P., Fijnvandraat K., Kasper C.K., White G., Santagostino E.,

Thromb. Haemost. 79:762-766(1998)

Diagnostic importance of the two-stage factor VIII:C assay demonstrated by a case of mild haemophilia associated with His1954-->Leu substitution in the factor VIII A3 domain

Keeling D.M., Sukhu K., Kemball-Cook G., Waseem N., Bagnall R., Lloyd J.V.,

Br. J. Haematol. 105:1123-1126(1999)

Screen of 55 Slovenian haemophilia A patients: identification of 2 novel mutations (S-1R and IVS23+1G-->A) and discussion of mutation spectrum

Strmecki L., Benedik-Dolnicar M., Vouk K., Komel R.,

Hum. Mutat. 13:413-413(1999)

Mutational-screening in the factor VIII gene resulting in the identification of three novel mutations, one of which is a donor splice mutation

Moeller-Morlang K., Tavassoli K., Eigel A., Pollmann H., Horst J.,

Hum. Mutat. 13:504-504(1999)

Start of UK confidential haemophilia A database: analysis of 142 patients by solid phase fluorescent chemical cleavage of mismatch

The haemophilia centres, Waseem N.H., Bagnall R., Green P.M., Giannelli F.,

Thromb. Haemost. 81:900-905(1999)

A novel cause of mild/moderate hemophilia A: mutations scattered in the factor VIII C1 domain reduce factor VIII binding to von Willebrand factor

Jacquemin M., Lavend'homme R., Benhida A., Vanzieleghem B., d'Oiron R., Lavergne J.-M., Brackmann H.H., Schwaab R., VandenDriessche T., Chuah M.K.L., Hoylaerts M., Gilles J.G.G., Peerlinck K., Vermylen J., Saint-Remy J.-M.R.,

Blood 96:958-965(2000)

Hemophilic factor VIII C1- and C2-domain missense mutations and their modeling to the 1.5-angstrom human C2-domain crystal structure

Liu M.-L., Shen B.W., Nakaya S., Pratt K.P., Fujikawa K., Davie E.W., Stoddard B.L., Thompson A.R.,

Blood 96:979-987(2000)

Intracellular accumulation of factor VIII induced by missense mutations Arg593-->Cys and Asn618-->Ser explains cross-reacting material-reduced haemophilia A

Roelse J.C., De Laaf R.T.M., Timmermans S.M.H., Peters M., Van Mourik J.A., Voorberg J.,

Br. J. Haematol. 108:241-246(2000)

Assay discrepancy in mild haemophilia A due to a factor VIII missense mutation (Asn694Ile) in a large Danish family

Schwaab R., Oldenburg J., Kemball-Cook G., Albert T., Juhler C., Hanfland P., Ingerslev J.,

Br. J. Haematol. 109:523-528(2000)

Experience of a single Italian center in genetic counseling for hemophilia: from linkage analysis to molecular diagnosis

Tagariello G., Belvini D., Salviato R., Are A., De Biasi E., Goodeve A., Davoli P.,

Haematologica 85:525-529(2000)

Relationship between factor VIII mutation type and inhibitor development in a cohort of previously untreated patients treated with recombinant factor VIII (Recombinate)

Recombinate PUP study group, Goodeve A.C., Williams I., Bray G.L., Peake I.R.,

Thromb. Haemost. 83:844-848(2000)

Mutations of the factor VIII gene in Thai hemophilia A patients

Akkarapatumwong V., Oranwiroon S., Pung-amritt P., Treesucon A., Thanootarakul P., Veerakul G., Mahasandana C., Panyim S., Yenchitsomanus P.,

Hum. Mutat. 15:117-118(2000)

Somatic mosaicism in hemophilia A: a fairly common event

Leuer M., Oldenburg J., Lavergne J.-M., Ludwig M., Fregin A., Eigel A., Ljung R., Goodeve A., Peake I., Olek K.,

Am. J. Hum. Genet. 69:75-87(2001)

Missense mutations causing mild hemophilia A in Iceland detected by denaturing gradient gel electrophoresis

Jonsdottir S., Diamond C., Levinson B., Magnusson S., Jensson O., Gitschier J.,

Hum. Mutat. 1:506-508(1992)

Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A

McGinniss M.J., Kazazian H.H. Jr., Hoyer L.W., Bi L., Inaba H., Antonarakis S.E.,

Genomics 15:392-398(1993)

Double strand conformation polymorphism (DSCP) detects two point mutations at codon 280 (AAC-->ATC) and at codon 431 (TAC-->AAC) of the blood coagulation factor VIII gene

Pieneman W.C., Reitsma P.H., Briet E.,

Thromb. Haemost. 69:473-475(1993)

Eleven novel mutations in the factor VIII gene from Brazilian hemophilia A patients

Arruda V.R., Pieneman W.C., Reitsma P.H., Deutz-Terlouw P.P., Annichino-Bizzacchi J.M., Brieet E., Costa F.F.,

Blood 86:3015-3020(1995)

Screening for mutations in haemophilia A patients by multiplex PCR-SSCP, Southern blotting and RNA analysis: the detection of a genetic abnormality in the factor VIII gene in 30 out of 35 patients

Pieneman W.C., Deutz-Terlouw P.P., Reitsma P.H., Brieet E.,

Br. J. Haematol. 90:442-449(1995)

Detection of mutations in ectopic factor VIII transcripts from nine haemophilia A patients and the correlation with phenotype

Bidichandani S.I., Lanyon W.G., Shiach C.R., Lowe G.D.O., Connor J.M.,

Hum. Genet. 95:531-538(1995)

Characterization of the factor VIII defect in 147 patients with sporadic hemophilia A: family studies indicate a mutation type-dependent sex ratio of mutation frequencies

Becker J., Schwaab R., Moeller-Taube A., Schwaab U., Schmidt W., Brackmann H.H., Grimm T., Olek K., Oldenburg J.,

Am. J. Hum. Genet. 58:657-670(1996)

Molecular characterization of haemophilia A in southern Chinese

Chan V., Pang A., Chan T.P.T., Chan V.W.-Y., Chan T.K.,

Br. J. Haematol. 93:451-456(1996)

Mutations in a subgroup of patients with mild haemophilia A and a familial discrepancy between the one-stage and two-stage factor VIII:C methods

Rudzki Z., Duncan E.M., Casey G.J., Neumann M., Favaloro E.J., Lloyd J.V.,

Br. J. Haematol. 94:400-406(1996)

Mutations in the FVIII gene in seven families with mild haemophilia A

Mazurier C., Gaucher C., Jorieux S., Parquet-Gernez A.,

Br. J. Haematol. 96:426-427(1997)

Factor VIII gene analysis in Japanese CRM-positive and CRM-reduced haemophilia A patients by single-strand conformation polymorphism

Morichika S., Shima M., Kamisue S., Tanaka I., Imanaka Y., Suzuki H., Shibata H., Pemberton S., Gale K., McVey J., Tuddenham E.G.D., Yoshioka A.,

Br. J. Haematol. 98:901-906(1997)

Mutational analysis of ectopic factor VIII transcripts from hemophilia A patients: identification of cryptic splice site, exon skipping and novel point mutations

Tavassoli K., Eigel A., Pollmann H., Horst J.,

Hum. Genet. 100:508-511(1997)

Recurrent mutations and three novel rearrangements in the factor VIII gene of hemophilia A patients of Italian descent

Casula L., Murru S., Pecorara M., Ristaldi M.S., Restagno G., Mancuso G., Morfini M., de Biasi R., Baudo F., Carbonara A.,

Blood 75:662-670(1990)

CRM+ haemophilia A due to a missense mutation (372-->Cys) at the internal heavy chain thrombin cleavage site

Pattinson J.K., McVey J.H., Boon M., Ajani A., Tuddenham E.G.,

Br. J. Haematol. 75:73-77(1990)

Characterization of mutations in the factor VIII gene by direct sequencing of amplified genomic DNA

Higuchi M., Wong C., Kochhan L., Olek K., Aronis S., Kasper C.K., Kazazian H.H. Jr., Antonarakis S.E.,

Genomics 6:65-71(1990)

Use of denaturing gradient gel electrophoresis to detect point mutations in the factor VIII gene

Traystman M.D., Higuchi M., Kasper C.K., Antonarakis S.E., Kazazian H.H. Jr.,

Genomics 6:293-301(1990)

Mutations and a polymorphism in the factor VIII gene discovered by denaturing gradient gel electrophoresis

Kogan S., Gitschier J.,

Proc. Natl. Acad. Sci. U.S.A. 87:2092-2096(1990)

Identification of mutations in two families with sporadic hemophilia A

Paynton C., Sarkar G., Sommer S.S.,

Hum. Genet. 87:397-400(1991)

Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene

Higuchi M., Kazazian H.H. Jr., Kasch L., Warren T.C., McGinniss M.J., Phillips J.A. III, Kasper C., Janco R., Antonarakis S.E.,

Proc. Natl. Acad. Sci. U.S.A. 88:7405-7409(1991)

Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis

Higuchi M., Antonarakis S.E., Kasch L., Oldenburg J., Economou-Petersen E., Olek K., Arai M., Inaba H., Kazazian H.H. Jr.,

Proc. Natl. Acad. Sci. U.S.A. 88:8307-8311(1991)

Detection and characterisation of two missense mutations at a cleavage site in the factor VIII light chain

Schwaab R., Ludwig M., Kochhan L., Oldenburg J., McVey J.H., Egli H., Brackmann H.H., Olek K.,

Thromb. Res. 61:225-234(1991)

GAA(Glu)272->AAA(Lys) and CGA(Arg)1941->CAA(Gln) in the factor VIII gene in two haemophilia A patients of Czech origin

Krepelova A., Vorlova Z., Acquila M., Mori P.,

Br. J. Haematol. 81:458-458(1992)

Detection of mutations in the factor VIII gene using single-stranded conformational polymorphism (SSCP)

Economou E.P., Kazazian H.H. Jr., Antonarakis S.E.,

Genomics 13:909-911(1992)

Screening for nonsense mutations in patients with severe hemophilia A can provide rapid, direct carrier detection

Reiner A.P., Thompson A.R.,

Hum. Genet. 89:88-94(1992)

A novel mutation (Arg-->Leu in exon 18) in factor VIII gene responsible for moderate hemophilia A

Nafa K., Baudis M., Deburgrave N., Bardin J.M., Sultan Y., Kaplan J.C., Delpech M.,

Hum. Mutat. 1:77-78(1992)

Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A

Diamond C., Kogan S., Levinson B., Gitschier J.,

Hum. Mutat. 1:248-257(1992)

The acidic region of the factor VIII light chain and the C2 domain together form the high affinity binding site for von Willebrand factor

Saenko E.L., Scandella D.,

J. Biol. Chem. 272:18007-18014(1997)

Locations of disulfide bonds and free cysteines in the heavy and light chains of recombinant human factor VIII (antihemophilic factor A)

McMullen B.A., Fujikawa K., Davie E.W., Hedner U., Ezban M.,

Protein Sci. 4:740-746(1995)

Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry

Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.,

J. Proteome Res. 4:2070-2080(2005)

Membrane-binding peptide from the C2 domain of factor VIII forms an amphipathic structure as determined by NMR spectroscopy

Gilbert G.E., Baleja J.D.,

Biochemistry 34:3022-3031(1995)

The molecular basis of hemophilia A

Gitschier J.,

Ann. N. Y. Acad. Sci. 614:89-96(1991)

Factor VIII gene and hemophilia A

White G.C. II, Shoemaker C.B.,

Blood 73:1-12(1989)

Molecular etiology of factor VIII deficiency in hemophilia A

Antonarakis S.E., Kazazian H.H. Jr., Tuddenham E.G.D.,

Hum. Mutat. 5:1-22(1995)

Identification of a missense mutation in the factor VIII gene of a mild hemophiliac

Gitschier J., Wood W.I., Shuman M.A., Lawn R.M.,

Science 232:1415-1416(1986)

A novel missense mutation in the factor VIII gene identified by analysis of amplified hemophilia DNA sequences

Levinson B., Janco R.L., Phillips J.A. III, Gitschier J.,

Nucleic Acids Res. 15:9797-9805(1987)

Nonsense and missense mutations in hemophilia A: estimate of the relative mutation rate at CG dinucleotides

Youssoufian H., Antonarakis S.E., Bell W., Griffin A.M., Kazazian H.H. Jr.,

Am. J. Hum. Genet. 42:718-725(1988)

Moderately severe hemophilia A resulting from Glu-->Gly substitution in exon 7 of the factor VIII gene

Youssoufian H., Wong C., Aronis S., Platokoukis H., Kazazian H.H. Jr., Antonarakis S.E.,

Am. J. Hum. Genet. 42:867-871(1988)

Purification and characterization of factor VIII 1,689-Cys: a nonfunctional cofactor occurring in a patient with severe hemophilia A

O'Brien D.P., Tuddenham E.G.,

Blood 73:2117-2122(1989)

An arginine to cysteine amino acid substitution at a critical thrombin cleavage site in a dysfunctional factor VIII molecule

Shima M., Ware J., Yoshioka A., Fukui H., Fulcher C.A.,

Blood 74:1612-1617(1989)

A novel missense mutation in exon 4 of the factor VIII:C gene resulting in moderately severe hemophilia A

Chan V., Chan T.K., Tong T.M., Todd D.,

Blood 74:2688-2691(1989)

Mild hemophilia A resulting from Arg-to-Leu substitution in exon 26 of the factor VIII gene

Inaba H., Fujimaki M., Kazazian H.H. Jr., Antonarakis S.E.,

Hum. Genet. 81:335-338(1989)

Direct characterization of factor VIII in plasma: detection of a mutation altering a thrombin cleavage site (arginine-372-->histidine)

Arai M., Inaba H., Higuchi M., Antonarakis S.E., Kazazian H.H. Jr., Fujimaki M., Hoyer L.W.,

Proc. Natl. Acad. Sci. U.S.A. 86:4277-4281(1989)

Characterization of a thrombin cleavage site mutation (Arg 1689 to Cys) in the factor VIII gene of two unrelated patients with cross-reacting material-positive hemophilia A

Arai M., Higuchi M., Antonarakis S.E., Kazazian H.H. Jr., Phillips J.A. III, Janco R.L., Hoyer L.W.,

Blood 75:384-389(1990)

Identification of factor VIII gene mutations in patients with severe haemophilia A in Venezuela: identification of seven novel mutations

Albanez S., Ruiz-Saez A., Boadas A., De Bosch N., Porco A.,

Haemophilia 17:913-918(2011)

Factor VIII Antigen, Activity, and Mutations in Hemophilia A

Nair P.S., Shetty S., Ghosh K.,

Clin. Appl. Thromb. Hemost. 22:381-385(2016)

Mild hemophilia A patient with novel Pro1809Leu mutation develops an anti-C2 antibody inhibiting allogeneic but not autologous factor VIII activity

Yada K., Nogami K., Takeyama M., Ogiwara K., Wakabayashi H., Shima M.,

J. Thromb. Haemost. 13:1843-1853(2015)

High throughput mutation screening of the factor VIII gene (F8C) in hemophilia A: 37 novel mutations and genotype-phenotype correlation

Citron M., Godmilow L., Ganguly T., Ganguly A.,

Hum. Mutat. 20:267-274(2002)

Non-inversion factor VIII mutations in 80 hemophilia A families including 24 with alloimmune responses

Liu M.-L., Nakaya S., Thompson A.R.,

Thromb. Haemost. 87:273-276(2002)

11 hemophilia A patients without mutations in the factor VIII encoding gene

Klopp N., Oldenburg J., Uen C., Schneppenheim R., Graw J.,

Thromb. Haemost. 88:357-360(2002)

Analysis of 18 novel mutations in the factor VIII gene

Bicocchi M.P., Pasino M., Lanza T., Bottini F., Boeri E., Mori P.G., Molinari A.C., Rosano C., Acquila M.,

Br. J. Haematol. 122:810-817(2003)

Thirty-four novel mutations detected in factor VIII gene by multiplex CSGE: modeling of 13 novel amino acid substitutions

Habart D., Kalabova D., Novotny M., Vorlova Z.,

J. Thromb. Haemost. 1:773-781(2003)

Genotype and phenotype of haemophilia A in Thai patients

Yenchitsomanus P., Akkarapatumwong V., Pung-Amritt P., Intorasoot S., Thanootarakul P., Oranwiroon S., Veerakul G., Mahasandana C.,

Haemophilia 9:179-186(2003)

Small FVIII gene rearrangements in 18 hemophilia A patients: five novel mutations

Bicocchi M.P., Pasino M., Lanza T., Bottini F., Molinari A.C., Caprino D., Rosano C., Acquila M.,

Am. J. Hematol. 78:117-122(2005)

Mutation analysis in 51 patients with haemophilia A: report of 10 novel mutations and correlations between genotype and clinical phenotype

Hill M., Deam S., Gordon B., Dolan G.,

Haemophilia 11:133-141(2005)

Female haemophilia A heterozygous for a de novo frameshift and a novel missense mutation of factor VIII

Cai X.-H., Wang X.-F., Dai J., Fang Y., Ding Q.-L., Xie F., Wang H.-L.,

J. Thromb. Haemost. 4:1969-1974(2006)

Identification of 31 novel mutations in the F8 gene in Spanish hemophilia A patients: structural analysis of 20 missense mutations suggests new intermolecular binding sites

Vencesla A., Corral-Rodriguez M.A., Baena M., Cornet M., Domenech M., Baiget M., Fuentes-Prior P., Tizzano E.F.,

Blood 111:3468-3478(2008)

Characterization of the polypeptide composition of human factor VIII:C and the nucleotide sequence and expression of the human kidney cDNA

Truett M.A., Blacher R., Burke R.L., Caput D., Chu C., Dina D., Hartog K., Kuo C.H., Masiarz F.R., Merryweather J.P., Najarian R., Pachl C., Potter S.J., Puma J., Quiroga M., Rall L.B., Randolph A., Urdea M.S., Ezban M.,

DNA 4:333-349(1985)

Characterization of tyrosine sulfate residues in antihemophilic recombinant factor VIII by liquid chromatography electrospray ionization tandem mass spectrometry and amino acid analysis

Severs J.C., Carnine M., Eguizabal H., Mock K.K.,

Rapid Commun. Mass Spectrom. 13:1016-1023(1999)

Sulfation of Tyr1680 of human blood coagulation factor VIII is essential for the interaction of factor VIII with von Willebrand factor

Leyte A., van Schijndel H.B., Niehrs C., Huttner W.B., Verbeet M.P., Mertens K., van Mourik J.A.,

J. Biol. Chem. 266:740-746(1991)

Identification and functional importance of tyrosine sulfate residues within recombinant factor VIII

Pittman D.D., Wang J.H., Kaufman R.J.,

Biochemistry 31:3315-3325(1992)

Synonyms

Description

Drug Information

Von Willebrand factor/coagulation factor VIII complex (human, Octapharma)

Antihemophilic factor/von Willebrand factor complex (Human, Grifols Biologicals)

Von Willebrand factor (LFB)

Factor VIII/von Willebrand factor (Bio Products Laboratory)

Von Willebrand factor (Recombinant)

Antihemophilic factor/von Willebrand factor (CSL Behring)

Human protein C (Baxalta)

Protein C activated (Kaketsuken/Teijin)

Recombinant human coagulation factor VIII for injection

Valoctocogene roxaparvovec

Giroctocogene fitelparvovec

SPK-8011

3K3A-APC

SHP-654

DTX-201

SPK-8016

AAV2-8-HLP-FVIII-V3 （University College London)

Human von Willebrand factor (Boya Bio-Pharmaceutical)

Human von Willebrand factor (Shandong Taibang Biological Products)

Human coagulation factor Ⅷ /Human von Willebrand factor (Shandong Taibang Biological Products)

Factor VIII gene therapy (Novartis)

Factor VIII gene therapy (Corautus Genetics)

TB-402

Factor VIII gene therapy (Chiron)

Drotrecogin alfa

Human fibrinogen/Human thrombin (Mallinckrodt)

References

Lithuanian haemophilia A and B registry comprising phenotypic and genotypic data

Site and type of mutations in the factor VIII gene in patients and carriers of haemophilia A

Mild haemophilia A discovered in a previously multi-operated 73-year-old man: characterization of a new mutation

Molecular pathology of haemophilia A in Turkish patients: identification of 36 independent mutations

Seven novel and four recurrent point mutations in the factor VIII (F8C) gene

Rapid hemophilia A molecular diagnosis by a simple DNA sequencing procedure: identification of 14 novel mutations

Skewed X-chromosome inactivation in monochorionic diamniotic twin sisters results in severe and mild hemophilia A

Factor VIII deficiency not induced by FVIII gene mutation in a female first cousin of two brothers with haemophilia A

Three novel point mutations causing haemophilia A

The identification and classification of 41 novel mutations in the factor VIII gene (F8C)

Identification of seven novel mutations of F8C by DHPLC

A domain mutations in 65 haemophilia A families and molecular modelling of dysfunctional factor VIII proteins

Protein truncation test: detection of severe haemophilia a mutation and analysis of factor VIII transcripts

Independent occurrence of the novel Arg2163 to His mutation in the factor VIII gene in three unrelated families with haemophilia A with different phenotypes

Fluorescent chemical cleavage of mismatches for efficient screening of the factor VIII gene

Identification of four novel mutations in the factor VIII gene: three missense mutations (E1875G, G2088S, I2185T) and a 2-bp deletion (1780delTC)

Molecular diagnostics of 15 hemophilia A patients: characterization of eight novel mutations in the factor VIII gene, two of which result in exon skipping

Use of denaturing gradient gel blots to screen for point mutations in the factor VIII gene

Precise carrier diagnosis in families with haemophilia A: use of conformation sensitive gel electrophoresis for mutation screening and polymorphism analysis

Factor VIII inhibitors in mild and moderate-severity haemophilia A