Asymptomatic Factor VII Deficiency in African Americans

Pollak, Eleanor S.; Russell, Theresa T.; Ptashkin, Beverly; Smith‐Whitley, Kim; Camire, Rodney M.; Bauer, Kenneth A.

doi:10.1309/36hq-36et-u7k8-muxt

Cited by 4 publications

(10 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mutation c.1091G>A, which precludes the change Arg304Gln, also known as FVII Padua, was found in four patients (11.8%) in this study, three in homozygous and one in heterozygous state. This mutation has already been described in patients from different countries such as Italy, England, Brazil, Israel and other Asian countries [2,16,21]. Patients 8, 9 and 33 presented discrepant levels of FVII:C, when the test was carried out with RBT (FVII:C <3.32%), and with HT (FVII:C >15%).…”

Section: Discussionmentioning

confidence: 69%

The molecular basis of low activity levels of coagulation factor VII: a Brazilian cohort

Rabelo

Jardim

Landau³

et al. 2015

Haemophilia

View full text Add to dashboard Cite

Inherited factor VII (FVII) deficiency is the most common among the rare bleeding disorders. It is transmitted as an autosomal recessive inheritance, due to mutations in the FVII gene (F7). Molecular studies of FVII deficiency are rare in non-Caucasian populations. The aim of the study was to evaluate the molecular basis behind low levels of FVII activity (FVII:C) levels in a cohort of Brazilian patients. A total of 34 patients with low FVII levels were clinically evaluated and submitted to laboratory tests, among these, prothrombin time and FVII:C, with different thromboplastins. All exons and intron/exon boundaries of F7 were amplified and sequenced. A total of 14 genetic alterations were identified, of which six were described previously, c.1091G>A, c.1151C>T, c.-323_-313insCCTATATCCT, c.285G>A, c.525C>T, c.1238G>A and eight (54.0%) and eight were new, c.128G>A, c.252C>T, c.348G>A, c.417G>A, c.426G>A, c.745_747delGTG, c.843G>A and c.805+52C>T. In addition to the mutation c.1091G>A, known as FVII Padua, the mutation c.1151C>T also presented discrepant FVII:C levels when tested with human and rabbit brain thromboplastin. There was no association between phenotype and genotype. Most of the identified genetic alterations found were polymorphisms. Low levels of FVII:C in this population were mostly related to polymorphisms in F7 and associated with a mild clinical phenotype. Mutation c.1151C>T was associated with discrepant levels of FVII:C using different thromboplastins, such as reported with FVII Padua.

show abstract

Section: Discussionmentioning

confidence: 69%

The molecular basis of low activity levels of coagulation factor VII: a Brazilian cohort

Rabelo

Jardim

Landau³

et al. 2015

Haemophilia

View full text Add to dashboard Cite

show abstract

“…In 2006, Pollak et al [3] described three African-American patients with FVII Padua, in whom the underlying defect was documented to be the same R304Q mutation described earlier by James et al [8]. Twelve additional African-American patients in the study by Pollak et al [3] were asymptomatic with discrepant laboratory studies for FVII deficiency, consistent with the FVII Padua phenotype, but no genotype information was available on those patients. Five patients of African origin, who were identified because of prolonged PTs and low FVII:C levels, were reported recently in an abstract form to have the R304Q mutation [10].…”

Section: Discussionmentioning

confidence: 92%

“…FVII variants have been recognized previously in African-American patients, but until recently, no data have existed on the precise amino acid alterations, which give rise to the phenotype consistent with FVII Padua in African-Americans [9]. In 2006, Pollak et al [3] described three African-American patients with FVII Padua, in whom the underlying defect was documented to be the same R304Q mutation described earlier by James et al [8]. Twelve additional African-American patients in the study by Pollak et al [3] were asymptomatic with discrepant laboratory studies for FVII deficiency, consistent with the FVII Padua phenotype, but no genotype information was available on those patients.…”

Section: Discussionmentioning

confidence: 99%

“…Activity measurements of FVII are low when assayed using RBT, as the extrinsic pathway activator, but are normal when assayed using ox brain thromboplastin or recombinant human TF (rHTF). Levels of FVII antigen (FVII:Ag) are typically normal in African-American patients with FVII Padua and, as noted, patients with this mutation usually report no bleeding history [3].…”

Section: Introductionmentioning

confidence: 86%

See 1 more Smart Citation

Asymptomatic factor VII deficiency: gene analysis and structure–function relationships

Kirkel

Lin²,

Fu³

et al. 2010

Blood Coagulation & Fibrinolysis

View full text Add to dashboard Cite

Factor VII Padua is a variant form of factor VII deficiency characterized by a prolongation of the prothrombin time (PT), when the assay is performed using rabbit brain thromboplastin. The PT is normal when performed using either human or ox brain thromboplastin reagents, or a recombinant human tissue factor-based thromboplastin. We report a case of an African-American woman with asymptomatic factor VII deficiency, who had a prolonged PT and factor VII activity levels of 5-8% using rabbit brain thromboplastin, but a normal PT and factor VII activity levels when measured using recombinant human brain thromboplastin or tissue factor. The amino acid substitution (R304Q), which gives rise to factor VII Padua, was found in our patient, making this only the fourth African-American case described to date with this mutation. Our report emphasizes the importance of identifying this benign form of factor VII deficiency in order to avoid unnecessary exposure of patients to treatment with either plasma-derived products or recombinant activated factor VII.

show abstract

“…Diversity in the clinical phenotype has been observed among subjects with identical genotypes. In addition, the correlation between the plasma FVII activity level and bleeding manifestation appears to be weak [1,6,7]. The underlying mechanism for this striking variation in bleeding diathesis is not known.…”

Section: Introductionmentioning

confidence: 99%

Use of thromboelastography and thrombin generation assay to predict clinical phenotype in patients with severe FVII deficiency

2013

View full text Add to dashboard Cite

Summary Bleeding tendency is weakly correlated with the activity of factor VII (FVII) in the plasma of patients with FVII deficiency. A laboratory method for predicting bleeding risk in patients with this coagulation disorder is lacking. We investigated whether global coagulation assays, specifically thromboelastography (TEG) and thrombin generation assay (TGA), could be used to predict bleeding risk. We also sought to identify factors that may explain the differences in bleeding phenotype observed among individuals with severe FVII deficiency. The study comprised 12 patients with severe FVII deficiency (FVII activity <1%). Eleven patients were homozygous for the Gln100Arg mutation and one patient was compound heterozygous. Clinically, 10 patients had increased haemorrhagic diathesis, whereas two patients were asymptomatic. Blood sampling was performed at baseline for TEG and TGA analyses. The platelet aggregation assay was performed and the plasma level of anticoagulation inhibitors and thrombophilic risk factors assessed. No difference in the TEG and TGA results was observed in all FVII‐deficient individuals. The level of free tissue factor pathway inhibitor was within the normal range and similar in symptomatic and asymptomatic subjects. None of the participants had the FV Leiden mutation, prothrombin gene mutation, or abnormal anticoagulant inhibitor levels. Asymptomatic subjects showed normal platelet aggregation. These data suggested that TEG and TGA were not suitable methods for predicting the clinical phenotype in FVII‐deficient subjects.

show abstract

Asymptomatic Factor VII Deficiency in African Americans

Cited by 4 publications

References 0 publications

The molecular basis of low activity levels of coagulation factor VII: a Brazilian cohort

The molecular basis of low activity levels of coagulation factor VII: a Brazilian cohort

Asymptomatic factor VII deficiency: gene analysis and structure–function relationships

Use of thromboelastography and thrombin generation assay to predict clinical phenotype in patients with severe FVII deficiency

Contact Info

Product

Resources

About