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Results for “Factor VII Deficiency”

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PubMed1993

A new method for factor VII deficient substrate preparation and coagulation studies in malaria.

A simplified technique using DEAE-cellulose chromatography for the preparation of factor VII deficient substrate was developed in order to reduce the high cost of individual factor VII assay in the routine coagulation laboratory. The substrate prepared from cryo-removed human and bovine plasma had a high correlation (r = 0.9929) with two of the most popular imported commercial substrates available (DADE, Ortho). When compared several other imported commercial substrates of equal quality, the prepared substrate was 3,000 to 6,000 times cheaper. Using the prepared factor VII deficient substrate along with other commercial substrates available, two hundred and fifty patients with malaria (fifty cases of P. vivax and two hundred cases of P. falciparum) were studied for coagulation and fibrinolysis abnormalities. Only P. falciparum infections showed prolonged PT and aPTT which correlated with the degree of parasitemia (r = 0.0972). Factors V, VII, and IX were the most sensitive parameters in the expression of coagulation defects and most coagulation abnormalities were due to liver involvement. Plasmin activity was normal in P. vivax patients but it was significantly increased in P. falciparum patients with > 5% parasitemia. Only two of the complicated cases of P. falciparum patients showed the evidence of DIC.

Blood Coagulation Disorders↗
PubMed2000

A new mutation in the HNF4 binding region of the factor VII promoter in a patient with severe factor VII deficiency.

Investigation of the molecular basis of a severe factor VII (fVII) deficiency revealed compound heterozygosity in the fVII gene. On the paternal allele the patient had 3 structural gene abnormalities frequently associated with fVII deficiency. A new mutation, a C to T transition at position -55 relative to the translational start site, was found on the maternal allele. The study demonstrates that this mutation partially impeded binding of the transcriptional activator, hepatic nuclear factor 4, to the fVII promoter while greatly reducing reporter gene expression in hepatic cells. (Blood. 2000;96:4370-4372)

Adult↗
PubMed1996

Congenital factor VII deficiency in a patient with an abdominal aortic aneurysm.

A patient with congenital factor VII deficiency underwent surgery for an inflammatory abdominal aortic aneurysm. No references in the literature have been found on the management of this coagulation defect in patients who require vascular surgery. We present one such case, with special reference to the perioperative management of factor VII replacement therapy.

Aged↗
PubMed2003

Prenatal exclusion of severe factor VII deficiency.

A nonconsanguineous asymptomatic couple, were identified as carriers of factor VII (FVII) deficiency when two of their newborn children died of massive intracranial hemorrhage secondary to severe congenital FVII deficiency. Complete sequence analysis of the factor VII (F7) gene in this couple indicated that the mother was heterozygous for an A to G transition at position -2 of the exon 5 acceptor splice site, and the father was heterozygous for a G to T transversion at position +1 of the exon 6 donor splice site. This information allowed us to exclude a compound heterozygous deficiency state in a subsequent pregnancy using PCR/direct sequencing of the F7 gene using DNA obtained from chorionic villi at 10 weeks' gestation. Our experience with the family reported here further supports the conclusion that mutation-specific detection is reliable in the prenatal exclusion of severe bleeding disorders.

Chorionic Villi Sampling↗
PubMed1982

Congenital factor VII deficiency. Clinical and laboratory characteristics of a newly discovered kindred.

Four generations of a newly discovered kindred suffering from congenital factor VII deficiency have been studied. The abnormality was transmitted as an autosomal recessive character and resulted in homozygotes with less than 1% factor VII procoagulant activity. Antibody neutralization tests using a monospecific rabbit anti-human factor VII antibody demonstrated the presence of factor VII antigen in excess of factor VII procoagulant activity. The disorder has therefore resulted from the presence of a functionally abnormal factor VII molecule and not from a true deficiency of this factor. When the plasmas from the homozygotes were tested in the prothrombin time test using human, rabbit and ox tissue thromboplastins, a progressive diminution in the ability of these reagents to detect the factor VII procoagulant deficiency was observed. These differences were however small and the complete insensitivity of ox brain thromboplastins that characterizes the factor VII Padua abnormality was not observed.

Adolescent↗
PubMed1994

Molecular analysis of Polish patients with factor VII deficiency.

We analyzed the mutations in patients from 10 Polish kindreds with a bleeding diathesis due to factor VII deficiency. Patients from eight families had plasma levels of factor VII coagulant activity (VII:C) and factor VII antigen (VII:Ag) that were less than 4% of normal. The coding sequence of the factor VII gene was amplified from genomic DNA by polymerase chain reaction (PCR). Sequencing demonstrated a C to T transition at position 10798 resulting in Ala294Val, a G to A transition at 10976 resulting in Arg353Gln, and a single bp deletion at 11125 to 11128 causing a frameshift mutation in the triplet encoding amino acid 404. Homozygosity for the three sequence alterations was confirmed with the restriction enzymes AvaII and MspI and allele specific PCR, respectively. A homozygous patient from a ninth family with levels of VII:C and VII:Ag of 4% and 17%, respectively, had Ala294Val and the frameshift mutation, but not Arg353Gln. Investigation of a homozygous patient from a tenth kindred with VII:C and VII:Ag of 11% and 47%, respectively, demonstrated Ala294Val and Arg353Gln, but not the frameshift mutation. Based on the above data, we conclude that the frameshift mutation in the codon for amino acid 404 is associated with marked reductions in VII:C, Arg353Gln can decrease plasma levels of factor VII in the presence of other mutations in the factor VII gene, and Ala294Val results in a dysfunctional factor VII molecule.

Alleles↗
PubMed2005

A case presenting concurrence of Marfan syndrome, Basedow's disease and Arg353Gln polymorphism-related factor VII deficiency.

We report the case of a 48-year-old Japanese man who suffered from Marfan syndrome with severe aortic regurgitation, mitral regurgitation and rapid atrial fibrillation, which were aggravated by hyperdynamic circulatory conditions associated with coexistent Basedow's disease. Furthermore, concurrence of Arg353Gln polymorphism-related factor VII deficiency was discovered at the preoperative assessments. Both of his two brothers suffered from Marfan syndrome; however they had no findings of Arg353Glu polymorphism-related factor VII deficiency or Basedow's disease. After normalization of thyroid function, he had successfully the operations of Bentall procedure: a composite prosthetic graft: replacement of both the ascending aorta and aortic valve, and mitral valve annuloplasty. No specific therapy such as fresh frozen plasma or factor VII replacement therapy was required. He completely returned to his business work 6 weeks after the operation. Concurrence of Marfan syndrome and factor VII deficiency induced by two-hit genomic abnormalities and furthermore Basedow's disease, which significantly compromised the pathophysiological condition of Marfan syndrome, is extremely rare.

Base Sequence↗
PubMed1985

Hereditary factor VII deficiency: heterogeneity defined by combined functional and immunochemical analysis.

Twenty-six patients with hereditary factor VII deficiency (VII:C less than 10%) were evaluated using a panel of three thromboplastins of varying species and tissue origin in both coagulant and chromogenic assay systems. Normal values for the coagulation and chromogenic assays were 104% +/- 7% and 108% +/- 21%, respectively. Factor VII antigen was measured by a specific radioimmunoassay (normal, 470 +/- 112 ng/mL). The patients were divided into two groups based on the factor VII:Ag assay results. Group 1, 18 patients, had decreased levels of factor VII:Ag and group 2, eight patients, had normal levels of factor VII:Ag. The two groups were further subdivided on the basis of discrepant factor VII:C levels in the chromogenic and coagulant assays. The number of observed patterns of functional factor VII:C activity suggests a high degree of complexity of factor VII and thromboplastin interaction. Whereas no clinical bleeding was reported in any of the nine black patients evaluated, all Caucasians (16) and one Hispanic presented with mild to severe bleeding. Patients with factor VII:C greater than 10% using a human thromboplastin had a negative bleeding history, regardless of the activity measured with other thromboplastins. Factor VII activity measured with a human thromboplastin appears to correlate best with the clinical picture.

Adolescent↗
PubMed2006

Pregnancy in women with congenital factor VII deficiency.

The aim was to review the pregnancy and obstetric outcome in women with factor VII (FVII) deficiency. The study group contained women with FVII deficiency, registered with Haemophilia centre and Haemostasis Unit at the Royal Free Hospital, London. The women were interviewed and case notes were reviewed. The main outcome measures were changes in FVII levels in pregnancy, maternal and perinatal outcome. The FVII levels ranged from 7-36 IU dL(-1) in the 13 women included in the study. There were a total of 14 pregnancies in seven women. Ten pregnancies in four women were prior to the diagnosis of FVII deficiency. Following the diagnosis of FVII deficiency, there were four pregnancies in three women. There was an increase in the FVII level during pregnancy in these women from a mean baseline level of 33 IU dL(-1) to a mean of 73 IU dL(-1). These women received recombinant FVIIa replacement during labour and delivery. There were two early pregnancy losses, both associated with excessive haemorrhage. There was only one postpartum haemorrhage in the study. There is a significant increase in FVII levels in pregnancy in women with heterozygous FVII deficiency. The risk of bleeding in early pregnancy might be higher than that at term, due to inadequate rise in the FVII level in early pregnancy.

Abortion, Spontaneous↗
PubMed1981

Factor VII deficiency: immunological characterization of genetic variants and detection of carriers.

Twenty-one patients with congenital factor VII deficiency belonging to 16 different kindreds were investigated. The existence of three immunochemical variants on the ground of factor VII activity (VII:C) and factor VII-related antigen (VII:Ag) levels (VII-, VII+ and VIIR) was established. There was no correlation between the presence of factor VII:Ag and either the clinical picture or the specific function as studied with the Km calculations. Genetically the model of inheritance is the same whatever the immunological variant, but the identification of carriers is simplified when the presence of factor VII-related antigen is assayed throughout a kindred.

Antigens↗
PubMed2003

[Molecular genetic analysis for a pedigree with severe hereditary coagulation factor VII deficiency].

OBJECTIVE: To identify the genetic mutations of a severe inherited coagulation factor VII (FVII) deficiency pedigree. METHODS: The diagnosis was validated by coagulant and haemostatic parameters. FVII gene mutations were screened in the propositus and his family members by DNA direct sequencing and confirmed by digestions of the restriction enzymes of the PCR production. RESULTS: Two heterozygous missense mutations were found in the propositus of the pedigree: a G to T transversion at position 9482 in exon 6 and a C to T mutation at position 11348 in exon 8 resulting in the amino acid substitution of Arg152 with Leu and Arg304 with Trp, respectively. A heterozygous single nucleotide deletion (C) at position 11487-11489(CCC) within exon 8 was identified, which predicted the frameshift mutation at position His351 followed by the changes of six corresponding amino acids and appearance of a premature protein caused by stop codon. The heterozygous mutations identified in the proband were derived from his father (Arg152 to Leu) and his mother (Arg304 to Trp mutation) and a heterozygous deletion (C) at position 11487-9(CCC). By tracing the other pedigree members, it was found that his grandmother had a heterozygous mutation of Arg304Trp and a heterozygous polymorphism of Arg353Gln and his grandfather had a heterozygous Arg152Leu mutation. CONCLUSION: Three heterozygous mutations were found in a pedigree with hereditary coagulation factor VII deficiency. Arg152Leu and deletion C at position 11487-9(CCC) were novel mutations.

Adult↗
PubMed1994

Molecular defects in CRM+ factor VII deficiencies: modelling of missense mutations in the catalytic domain of FVII.

The molecular defects causing CRM+ factor VII deficiency were investigated in seven unrelated subjects and several members of their families. Four missense mutations located in the catalytic domain of factor VII were found. The previously reported 304Arg-->Gln substitution was present in the homozygous and heterozygous forms, with different polymorphic haplotypes, thus demonstrating that it is recurrent and frequent in the Italian population. The 310Cys-->Phe substitution was found in the homozygous form and in the compound heterozygous condition with the nonsense mutation 356Trp-->stop. Two missense mutations, 298Met-->Ile and 342Gly-->Arg, were found in the homozygous and in the heterozygous condition respectively. Molecular heterogeneity was further increased by finding of the 353Arg-->Gln polymorphism in the doubly heterozygous condition with the 304 and 342 mutations. Plausible explanations for loss of FVII function were found by inspecting a model of the serine protease domain of factor VIIa. Inefficient activation of the catalytic site is predicted for 298Met-->Ile. 342Gly-->Arg would directly distort the geometry of the 'oxyanion hole' preventing formation of a substrate enzyme intermediate. 310Cys-->Phe is predicted to have an adverse effect on tissue factor interaction. These mutations point to important regions of the factor VII molecule.

Antigens↗
PubMed2006

A coagulation factor VII deficiency protects against acute inflammatory responses in mice.

Upregulation of the activated Factor VII (FVIIa)/Tissue Factor complex, downregulation of natural anticoagulation pathways, and inhibition of fibrinolysis, are major contributors to coagulopathies associated with acute inflammation. Provision of FVIIa, and consequent downstream coagulation-related proteases, also stimulates further inflammatory changes, which can result in disseminated intravascular coagulation. Thus, the potential protective effects in vivo of a genetic-based reduction in FVII levels have been investigated in a murine model of acute inflammation, namely lipopolysaccharide (LPS)-induced lethal endotoxaemia. Mice with a total FVII deficiency do not survive the neonatal period. Therefore mice expressing low levels of FVII (FVII(tTA/tTA)), producing sufficient amounts of FVII for survival (approximately 5% of wild-type (WT) FVII), were employed to investigate in vivo pathways involved in the crosstalk between coagulation, inflammation, and survival, consequent to administration of a lethal dose of LPS. The FVII(tTA/tTA) mice presented with reduced mortality, coagulation, and inflammatory responses in comparison with similarly treated WT mice after administration of LPS. The attenuated inflammatory responses in FVII(tTA/tTA) mice were associated with downregulation of Egr-1 signalling. Administration, in vivo, of specific inhibitors of FXa and thrombin demonstrated that the inflammatory responses were unaltered in WT mice, but further reduced in FVII(tTA/tTA) mice. Therefore, a FVII deficiency enhances survival from lethal endotoxaemia both through attenuation of inflammatory responses that result directly from reduced FVIIa levels, and, indirectly, from downregulation of coagulation proteases downstream of the FVII-dependent cascade.

Ancrod↗
PubMed2004

[Double heterozygous mutations of non-canonical splice (IVS1a + 5g > a) and His348Gln caused inherited coagulation factor VII deficiency].

OBJECTIVE: To investigate the pathogenesis of inherited coagulation factor VII (FVII) deficiency. METHODS: The diagnosis was validated by coagulant parameter assay. FVII gene mutations were analysed in the proband by DNA direct sequencing of PCR products of all exons, exon-intron boundaries and the 3', 5'untranslated sequences. The mutations were confirmed by reverse sequencing. The ectopic transcripts of RT-PCR were used to confirm the characteristics of the mutation in non-canonical splice site (IVS1a + 5g > a). RESULTS: Double heterozygous mutations in the propositus were identified: a T to G mutation at position 10961, resulting in His348Gln substitution, a non-canonical splice site (IVS1a + 5g > a) mutation, causing the new model of splice and frameshift mutation. CONCLUSION: Double heterozygous mutations of His348Gln and IVS1a + 5g > a were identified in a propositus, the splicing pattern of the IVS1a + 5g > a mutation was reported for the first time.

Amino Acid Sequence↗
PubMed1986

Selection of replacement therapy for patients with severe factor VII deficiency.

The risk of significant bleeding in patients with severe Factor VII (FVII) deficiency is well documented. However, controversy regarding management exists not only for the choice of FVII replacement product, but also for the desired hemostatic level of FVII. Two case reports are presented where fresh frozen plasma (FFP) and several Factor IX (FIX) complex concentrates were used to achieve hemostasis. Significantly higher FVII levels were achieved with Proplex (FIX Complex, Hyland Therapeutics) than with other products. Although this and other reports indicate that minor bleeding can be controlled with levels of FVII under 15%, life-threatening hemorrhages require higher FVII levels that can be attained only by using a product with a significant FVII content. It is important to know the FVII content of FIX concentrates in order to plan appropriate therapy for patients with FVII deficiency.

Blood Coagulation Factors↗
PubMed1988

Hereditary blood coagulation factor-VII deficiency: a comparison of the defect in beagles from several sources.

1. Hereditary blood coagulation factor-VII deficiency has previously been identified in Beagles from a number of sources in Britain and North America. 2. A study is now reported in which the nature of the defect is compared in plasma samples from these sources. 3. When prothrombin times and Russell's Viper venom clotting times were determined on mixtures of samples, no cross-correction of the defective coagulation activity was detected. 4. Antibody neutralization assays of factor-VII related antigen and assays of factor-VII procoagulant activity revealed essentially similar levels in all samples. 5. Thus no significant genetic variants of the defect were identified.

Animals↗