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Results for “Factor VII Deficiency”

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At least 127 records · Page 7Linked to original sources
PubMed2006

A novel missense mutation responsible for factor VII deficiency in research Beagle colonies.

BACKGROUND: Canine factor VII (cFVII) deficiency, an autosomal recessive trait originally identified in research Beagles, is associated with a mild to moderate bleeding tendency. OBJECTIVE: Our aim was to identify and characterize the mutation causing cFVII deficiency. METHODS: In order to sequence the coding regions of the cFVII gene, we cloned the cFVII cDNA. Genomic DNA and plasma from FVII-deficient Beagles and obligate carriers were utilized. RESULTS: In all FVII-deficient dogs, we identified a single causative G to A missense mutation in exon 5, encoding the second epidermal growth factor-like domain, resulting in substitution of glycine 96 by glutamic acid, with plasma FVII coagulant activity of <or = 4% in affected Beagles. In vitro expression indicated that the majority (96%) of cFVII-G96E protein was retained intracellularly. In addition, analysis of purified recombinant wild-type and mutant cFVII proteins demonstrated reduced activity of the mutant (< 2%) compared with wild-type. Rotational thromboelastometry revealed a severe impairment of clotting activity in affected Beagles, and heterozygotes also exhibited changes in coagulation-based assays. Using a mutation-specific polymerase chain reaction/restriction digest that allows rapid identification of the G96E mutation, we surveyed a US research Beagle colony and identified a mutant allelic frequency of 31%. CONCLUSIONS: We have identified a single causative mutation for cFVII deficiency that may have implications for pharmacotoxicologic research, because reduced FVII coagulant activity may alter hemostatic and/or cardiovascular endpoints in this commonly used animal species.

Amino Acid Sequence↗
PubMed1988

Arthropathy and surgery in congenital factor VII deficiency.

A 35-year-old woman with severe (less than 1 percent) factor VII deficiency had recurrent hemarthroses involving the left knee, leading to deformity, pain, and virtually complete loss of function. It was elected to perform a total knee replacement. In preparation for surgery, the patient received heat-treated prothrombin complex concentrate containing 870 units of factor VII per vial. A dose of 50 U/kg raised the factor VII level to 115 percent. At surgery, dense adhesions were found within the joint, the articular cartilage was overgrown with pannus extending out to the lateral patella, and there was extensive deformity of the femoral condyle and tibial plateau. The joint was excised and replaced by a cemented Microloc prosthesis. Postoperatively, factor VII levels were maintained above 10 percent by six-hourly infusions of concentrate. Beginning on Day 4, single daily infusions of 25 U/kg were given prior to physical therapy. No bleeding occurred, and the patient was ambulating at the time of discharge 20 days postoperatively. This experience indicates that despite its short half-life (less than four hours), factor VII levels sufficient to prevent bleeding can be maintained in factor VII-deficient patients undergoing major operative procedures.

Adult↗
PubMed1994

Acquired factor VII deficiency associated with pleural liposarcoma.

Isolated acquired factor VII (FVII) deficiency (0.15 U/ml) was identified in a 30-year-old man with pleural liposarcoma. The patient underwent surgery with continuous FVII concentrate infusion. No anti-FVII antibody or FVII/anti-FVII complex was detected. However, the short half-life and low recovery of FVII after concentrate infusion suggested the presence of an antibody. Whatever the mechanism, this FVII deficiency was related to the presence of the liposarcoma. FVII level normalized during tumour regression and fell again when the liposarcoma relapsed.

Adult↗
PubMed2006

Asymptomatic factor VII deficiency in African Americans.

African Americans with factor VII (FVII) deficiency, as defined by clinical laboratory values, are frequently asymptomatic. To date the genotypes underlying this FVII defect in asymptomatic African Americans have not been established. We show in 3 unrelated African-American patients that the defect is due to a G to A nucleotide change resulting in an arginine to glutamine mutation in Factor VII amino acid 304. This defect results in low FVII coagulant activity levels using rabbit brain thromboplastin but not using human thromboplastin. This report may aid transfusion and hematology specialists evaluate patient results and prevent unnecessary transfusions to treat patients with abnormal laboratory values.

Adolescent↗
PubMed1984

Hereditary factor VII deficiency: report of a case of intracranial hemorrhage.

A case of factor VII deficiency in a 52-year-old woman who developed central nervous system hemorrhage is here reported. Screening coagulation tests were all normal except for prothrombin time, normotest and thrombotest. Specific assays of vitamin K-dependent factors revealed that factor VII activity was reduced (11 U/dl). The studies of the family demonstrated that 2 sisters out of 4 were heterozygous for the defect. The activity of factor VII in the offspring, classified as obligatory carriers, ranged between 62 and 78 U/dl, the antigen between 55 and 75 U/dl. The wide variability of factor VII in normal people and the possible compensative effect of normal alleles in carriers do not allow to define the variant, namely if the patient is a CRMR homozygote or a CRMR/CRM-double heterozygote.

Antigens↗
PubMed1983

Warfarin-induced factor VII deficiency and the bleeding time.

The effect of warfarin-induced factor VII deficiency on the skin bleeding time was investigated in 10 consecutive patients with mean prothrombin times of 33 sec and factor VII levels of 7%. Bleeding times in all but one subject were entirely within the normal range. We conclude that warfarin administration, even to the point of prolonging the prothrombin time beyond the therapeutic range, is not associated with an abnormal bleeding time. Furthermore, from the above evidence and a review of the literature, it is considered doubtful that factor VII plays a major role in primary hemostasis.

Bleeding Time↗
PubMed1993

Molecular analysis of factor VII deficiency in Italy: a frequent mutation (FVII Lazio) in a repeated intronic region.

Molecular defects and polymorphic haplotypes of coagulation factor VII gene were studied in eight unrelated Italian subjects with factor VII deficiency, seven having the factor VII- variant, one the factor VIIR variant. An intron 7 mutation, which alters the consensus donor splice site sequence, was found in six subjects. The presence of the founder effect is suggested by their common geographical origin (a mountain area in the Lazio region) and by the identical polymorphic haplotype underlying the mutation. A different mutation, also located in the 5' monomer of the repeated intron 7 sequence, was found in the heterozygous condition in a subject from Northern Italy. New polymorphic alleles were detected in the repeated intron 7 region in subjects from Eastern Africa. Two missense mutations in codon 97 (Gly-->Cys, Gly-->Ser), the first found in the compound heterozygous condition with the frequent intron 7 mutation, suggest the presence of a hot spot mutation site in the second epidermal growth factor domain. Two neutral dimorphisms at codon 333Ser and 115His were detected, the last in linkage disequilibrium with the 353Arg/Gln polymorphism, and showing differences in frequency in the FVII deficient and control subjects.

Base Sequence↗
PubMed1991

Occurrence of hereditary leaky red cell syndrome and partial coagulation factor VII deficiency in a Spanish family.

A Spanish family was found to have the coexistence of a hereditary haemolytic syndrome associated with excessively leaky RBC membrane to sodium (Na+) and potassium (K+) cations and a partial coagulation factor VII deficiency. Haemolysis was mild in the propositus and the RBC membrane leak included a marked increase in passive permeability to Na+ and K+. This was associated with an increase in active Na+,K(+)-pump activity and in the ouabain-resistant fluxes: Na+, K(+)-cotransport and Na+, Li(+)-countertransport. Factor VII deficiency was of 50% and no clinical expression of the coagulation deficiency was observed. The family study revealed slightly abnormal RBC membrane cationic fluxes only in the father and decreased coagulation factor VII activity of 67% in the mother. Both parents were clinically and haematologically normal. It is suggested that the propositus has inherited the abnormal gene for leaky RBC syndrome from the father and the partial coagulation factor VII deficiency from the mother.

Anemia, Hemolytic, Congenital↗
PubMed1999

Factor VII deficiency rescues the intrauterine lethality in mice associated with a tissue factor pathway inhibitor deficit.

Mice doubly heterozygous for a modified tissue factor pathway inhibitor (TFPI) allele (tfpi delta) lacking its Kunitz-type domain-1 (TFPI+/delta) and for a deficiency of the factor VII gene (FVII+/-) were mated to generate 309 postnatal and 205 embryonic day 17.5 (E17. 5) offspring having all the predicted genotypic combinations. Progeny singly homozygous for the tfpidelta modification but with the wild-type fVII allele (FVII+/+/TFPIdelta/delta), and mice singly homozygous for the fVII deficiency and possessing the wild-type tfpi allele (FVII-/-/TFPI+/+), displayed previously detailed phenotypes (i.e., a high percentage of early embryonic lethality at E9.5 or normal development with severe perinatal bleeding, respectively). Surprisingly, mice of the combined FVII-/-/TFPIdelta/delta genotype were born at the expected mendelian frequency but suffered the fatal perinatal bleeding associated with the FVII-/- genotype. Mice carrying the FVII+/-/TFPIdelta/delta genotype were also rescued from the lethality associated with the FVII+/+/TFPIdelta/delta genotype but succumbed to perinatal consumptive coagulopathy. Thus, the rescue of TFPIdelta/delta embryos, either by an accompanying homozygous or heterozygous FVII deficiency, suggests that diminishment of FVII activity precludes the need for TFPI-mediated inhibition of the FVIIa/tissue factor coagulation pathway during embryogenesis. Furthermore, the phenotypes of these combined deficiency states suggest that embryonic FVII is produced in mice as early as E9.5 and that any level of maternal FVII in early-stage embryos is insufficient to cause a coagulopathy in TFPIdelta/delta mice.

Animals↗
PubMedDate not supplied

Isolated factor VII deficiency diagnosed after a life-threatening brain haemorrhage.

A 65-year-old man was admitted to another hospital with a life-threatening brain haemorrhage, and laboratory examinations on admission revealed prolonged prothrombin time with normal activated partial thromboplastin time. To establish the cause of his abnormal coagulation, he was referred to our clinic. Neither the patient nor his family had any previous history of bleeding symptoms. His liver function was within normal limits but coagulation tests showed increased plasma activities of factors II, VIII, IX, X, with reduced activities of factors V and VII. The activity of factor VII was less than 2% but no inhibitor of factor VII was detected in the plasma. We concluded that the patient had a rare congenital isolated factor VII deficiency although he had not shown earlier bleeding problems, presumably because of compensation for the factor VII deficiency by enhanced activities of components of the extrinsic coagulation pathway, factors II, VIII, IX and X.

Aged↗
PubMed2002

Acquired factor VII deficiency in hematopoietic stem cell transplant recipients.

Acquired factor VII (FVII) deficiency in the absence of vitamin K deficiency, oral anticoagulant therapy, synthetic liver dysfunction, or DIC is rare, with only a handful of cases thus far reported. In the period from 1990 to 1996 we identified eight patients with acquired FVII deficiency, all of whom presented with prolongation of the prothrombin time (PT) in the first 2 weeks following stem cell transplantation (SCT). The mean plasma FVII clotting activity (FVII:c) was 22% (range 8-35%) with an approximately equivalent reduction in FVII antigen (FVII:Ag) level. Mean plasma levels of fibrinogen and factors II, V, IX, and X were normal. Protein C activity was significantly depressed in only one of the three patients in whom it was measured. Several patients experienced bleeding complications, and hemorrhage directly accounted for death in two cases. Veno-occlusive disease of the liver developed in three patients. We conclude that FVII deficiency should be considered in the differential diagnosis of prolonged PT in patients who have recently undergone SCT. The mechanism of this acquired deficiency state remains to be defined.

Adult↗
PubMed1999

Factor VII deficiency in a mixed breed dog.

Abnormal bleeding following routine orchectomy of a 5-month-old mixed breed was determined to be due to factor VII deficiency. Although pedigree information was unavailable, failure to respond to vitamin K therapy and the absence of a plasma coagulation inhibitor suggested that the factor VII deficiency was likely inherited rather than acquired.

Animals↗
PubMed2000

[Genetic analysis of hereditary factor VII deficiency from a Chinese pedigree].

OBJECTIVE: To identify the mutation in coagulation factor VII gene from a Chinese patient with hereditary coagulation factor VII deficiency. METHODS: The genomic DNA fragments of FVII gene from a propositus and normal subjects were amplified using polymerase chain reaction (PCR), and analyzed with direct sequencing of PCR products. The PCR amplified genomic DNA fragments of FVII gene from the propositus and her family members were analyzed using restriction enzyme Hgic I. RESULTS: The FVII gene sequences of normal subjects were identical to the data published, while a missense mutation (TGT-->GGT) was found at codon 329 in FVII gene of the propositus. The heterozygous condition for the mutation was revealed in her three family members. CONCLUSION: We have found a novel mutation (TGT-->GGT) at codon 329 in FVII gene of a patient with hereditary FVII deficiency, which leads to a cystein residue replaced by a glysine. PCR combined with restriction enzyme Hgic I digestion would be a rapid diagnostic method for this mutation.

Factor VII↗
PubMed1998

Severe factor VII deficiency due to a mutation disrupting an Sp1 binding site in the factor VII promoter.

We have identified a point mutation in the promoter of the factor VII gene responsible for a severe bleeding disorder in a patient from a large French-Canadian family with known consanguinity. The proband has an extremely low plasma level of factor VII antigen and factor VII coagulant activity (<1 percent of normal) and suffers from hemarthroses and chronic arthropathy. Sequencing of the patient's factor VII 5' flanking region, intron/exon junctions, and coding regions showed a homozygous point mutation, a C to G transversion at position -94 relative to the translation start site. We show here that this mutation prevented binding of transcription factor Sp1 and of other nuclear proteins to this region of the factor VII promoter and resulted in a 20-fold reduction in reporter gene expression in HepG2 cells. These data underscore the importance of this region of the factor VII promoter for in vivo expression of the factor VII gene.

Adult↗
PubMed2002

Factor VII deficiency and a copper metabolism disorder in a patient with Klippel-Trenaunay syndrome.

We report on a patient with Klippel-Trenaunay (KT) syndrome, a factor VII deficiency and a copper metabolism disorder. The KT syndrome involved the left leg and, histologically, the liver. Dermatological examination, duplex ultrasonography and a skin and liver biopsy verified the KT syndrome. A long prothrombin time prompted clotting studies revealing a factor VII deficiency while the other factors were in the normal range. Further laboratory examinations showed a copper metabolism disorder similar to Wilson's disease with a low serum ceruloplasmin level, elevated copper concentration in the urine and increased copper deposition in the liver. Neither liver cirrhosis nor a Kayser-Fleischer corneal ring was present. Sequencing analysis of the Wilson's disease gene ATB7B showed no mutations. The occurrence of these three uncommon pathologies in a single patient has not been described to date, which may suggest a mutation in a hypothetical common regulatory gene leading to this unusual phenotype.

Adult↗