Factor VII Congenital Deficiency

Mariani, Guglielmo; Mazzucconi, M. G.

doi:10.1159/000214723

Cited by 31 publications

(13 citation statements)

References 8 publications

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“…Since factor VII de®ciency is a congenital defect of blood coagulation like factor VIII and IX de®ciencies, one would expect similar clinical symptoms. Our patients and those of Mariani & Mazzucconi [6], which make the two largest series of patients with severe or moderate factor VII de®ciency reported (28 and 24 cases, respectively), are not totally consistent with this prediction. In both studies a most prevalent symptom was epistaxis ( Table 2).…”

Section: Discussioncontrasting

confidence: 85%

Clinical manifestations in 28 Italian and Iranian patients with severe factor VII deficiency

Peyvandi

Asti

et al. 1997

Haemophilia

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There has been wide variation in the reported haemorrhagic manifestations of factor VII deficiency. We examined type and frequency of clinical manifestations in 28 Iranian and Italian patients with severe deficiency (factor VII coagulant activity 2% or less). The most frequent symptoms were epistaxis and menorrhagia, whereas soft tissue bleeding such as haemarthrosis and muscle haematoma was less frequent. Only 5 of 9 patient who underwent surgery without factor VII replacement therapy had postoperative bleeding severe enough to require blood transfusion. No thrombotic manifestation occurred. A factor VII functional assay based on the use of human thromboplastin was a better predictor of the bleeding tendency of these patients than a rabbit thromboplastin-based functional assay or immunoassay. On the whole, this study shows that in severe factor VII deficiency bleeding in mucosal tracts is not uncommon. Surgery can sometimes be performed without replacement therapy and without haemorrhagic complications.

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Section: Discussioncontrasting

confidence: 85%

Clinical manifestations in 28 Italian and Iranian patients with severe factor VII deficiency

Peyvandi

Asti

et al. 1997

Haemophilia

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“…Based on an inhibition neutralization assay using heterologous antisera to Factor VII, three immunologic variants ofFactor VII deficiency have been described (17). In the VII-variant, detectable cross-reacting material (CRM)' is absent.…”

Section: Introductionmentioning

confidence: 99%

Monoclonal anti-human factor VII antibodies. Detection in plasma of a second protein antigenically and genetically related to factor VII.

Broze¹,

Hickman²,

Miletich³

1985

J. Clin. Invest.

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Several murine monoclonal anti-human Factor VII antibodies were produced using hybridoma technology. Two noncompetitive monoclonal antibodies were used to examine by Western blotting the Factor VII cross-reactive material (CRM) in normal human plasma and three commercially available congenitally Factor VIIdeficient plasmas, and to construct a facile "sandwich" immunoassay for plasma Factor VII. A second, previously undescribed, form of Factor VII CRM was detected in human plasma, which on Western blotting stained with an apparent intensity 5-8% that of Factor VII. This glycoprotein, tentatively called VII*, has a molecular weight 4,500 D less than Factor VII, lacks detectable Factor VII functional activity, does not bind to barium citrate, and is not recognized by a monoclonal antibody that recognizes Factor VII but not a-chymotrypsin-treated Factor VII. VII* was not proteolytically produced from Factor VII during in vitro coagulation or after infusion of human Factor VII into rabbits. As determined by Western blotting, the human hepatoma cell line, HepG2, cultured in the presence of vitamin K, secreted relatively greater levels of VII* in proportion to VII (75%) than that found in human plasma. Warfarin treatment of HepG2 cells decreased the quantity of VII secreted by 77%, whereas it only inhibited the secretion of VII* by 14%. Immunologic studies of the plasmas from a patient on chronic warfarin therapy and an individual given a short course of high dose warfarin therapy corroborated the in vitro synthetic studies obtained with HepG2 cells. The data are consistent with the production of VII* by posttranslational, proteolytic, modification of VII, that, at least in the HepG2 cells studied, occurs intracellularly. However, other mechanisms for the production of VII*, in particular, alternative RNA splicing of the transcript from a single gene, cannot be excluded.

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“…However, very low levels of this zymogen (Ͻ2% of normal) are associated with severe coagulation disorders (18 -22). The clinical manifestations of less severe deficiencies are variable (18,19,(23)(24)(25). Such observations suggest that only low levels of fVII activity are required to maintain hemostasis in unchallenged patients.…”

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confidence: 99%

Characterization of Transcriptional Regulatory Elements in the Promoter Region of the Murine Blood Coagulation Factor VII Gene

Stauffer

Chukwumezie

Wilberding

et al. 1998

Journal of Biological Chemistry

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To identify the 5 sequences of the murine coagulation factor VII (fVII) gene that resulted in its efficient transcription, a variety of 5-flanking sequences up to 7 kilobase pairs upstream of the translation ATG initiation codon were fused to the reporter gene, bacterial chloramphenicol acetyltransferase, and relative expression levels of this gene in mouse Hepa 1-6 cells were determined. It was found that the 5 region extending approximately 85 base pairs (bp) upstream of the transcriptional initiation site served as the minimal DNA region that provided full relative promoter activity for chloramphenicol acetyltransferase expression. This region of the gene also contains consensus sequences for liverenriched transcription factors, C/EBP␤ and HNF4, as well as for the ubiquitous protein factors, AP1, H4TF1, NF1, and Sp1. In vitro DNase I footprinting of the 200-bp proximal region of the promoter with a murine Hepa 1-6 cell nuclear extract revealed a clear footprint of a region corresponding to ؊80 to ؊28 bp of the murine fVII gene, suggesting that liver factors interact with this region of the DNA. Competitive gel shift and supershift assays with different synthetic oligonucleotide probes demonstrate that proteins contained in the nuclear extract, identified as C/EBP␤, H4TF1, and HNF4, bind to a region of the murine fVII DNA from 85 to 32 bp upstream of the transcription start site. Purified Sp1 also interacts with this region of the DNA at a site that substantially overlaps, but is not identical to, the H4TF1 binding locus. Binding of Sp1 to the mouse DNA was not observed with the nuclear extract as the source of the transcription factors, suggesting that Sp1 is likely displaced from its binding site by H4TF1 in the crude extract. In vivo dimethyl sulfate footprint analysis confirmed the existence of these sites and additionally revealed two other binding regions slightly upstream of the CCAAT/enhancer-binding protein (C/EBP) binding locus that are homologous to NF1 binding sequences. The data demonstrate that appropriate transcription factor binding sites exist in the proximal promoter region of the murine fVII gene that are consistent with its strong liverbased expression in a highly regulated manner.

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Factor VII Congenital Deficiency

Cited by 31 publications

References 8 publications

Clinical manifestations in 28 Italian and Iranian patients with severe factor VII deficiency

Clinical manifestations in 28 Italian and Iranian patients with severe factor VII deficiency

Monoclonal anti-human factor VII antibodies. Detection in plasma of a second protein antigenically and genetically related to factor VII.

Characterization of Transcriptional Regulatory Elements in the Promoter Region of the Murine Blood Coagulation Factor VII Gene

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