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:10.1309/36hq36etu7k8muxt

Cited by 12 publications

(5 citation statements)

References 19 publications

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“…This mutation has already been described in patients from different countries such as Italy, England, Brazil, Israel and other Asian countries [2,16,21]. This mutation has already been described in patients from different countries such as Italy, England, Brazil, Israel and other Asian countries [2,16,21].…”

Section: Discussionmentioning

confidence: 77%

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

Rabelo

Jardim

Landau³

et al. 2015

Haemophilia

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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.

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Section: Discussionmentioning

confidence: 77%

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

“…The concomitant presence of c.1238G>A and c.-323_-313insCCTATATCCT polymorphisms may further reduce the FVII levels compared with the presence of each alone [8,36]. c.795_805+26 [7] is an intronic indel of exon 8, and its wild type is VNTR[6] [3]. This mutation is a common polymorphism in different populations which contributes to decreased FVII levels [37].…”

Section: Discussionmentioning

confidence: 99%

“…In forward sequencing, Arrow donates the G to A change, and in reverse sequencing, it donates the C to T change. [5]; h7, variant of c. 795_805þ26 [7].…”

Section: Discussionmentioning

confidence: 99%

“…In this context, evaluation of the FVII activity (FVII:C) by a PT-based assay using rabbit thromboplastin may appear to decreased; while using human thromboplastin and ox thromboplastin, the results are slightly reduced and normal, respectively. However, regardless of the method used, the FVII antigen (FVII:Ag) is normal [6,7]. Concordantly, different PT results may be obtained using different sources of thromboplastin.…”

Section: Introductionmentioning

confidence: 99%

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Factor VII Padua in Iran: clinical and laboratory findings of three unrelated patients

Shams

Hassani

Dorgalaleh³

et al. 2023

Blood Coagulation &Amp; Fibrinolysis

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The congenital factor VII (FVII) deficiency with an estimated incidence of one per 300 000 is the most common rare congenital bleeding disorder. The heterogeneous clinical pictures, including asymptomatic to life-threatening manifestations, are seen in patients with FVII deficiency. A variety of gene variants throughout the FVII (F7) gene have been reported so far. In this setting, very rare FVII Padua polymorphism provokes an interesting condition in which results of prothrombin time and FVII activity are different based on the thromboplastin sources used in these tests. The current study aimed to report the phenotype and genotyping of patients with Padua variant. During the workup of the laboratory for FVII deficiency for diagnosis of FVII Padua, all patients with FVII deficiency who had prolonged prothrombin time, normal activated partial thromboplastin time, and variable FVII activity results using different sources of thromboplastin were included. Demographic data and clinical findings were recorded. For the molecular study, the F7 gene sequencing was performed using the Sanger sequencing technique. Five patients with FVII Padua and a history of mild-to-moderate bleeding, including easy bruising, epistaxis, gingivorrhagia, and bleeding after surgical challenges (including dental extraction and tonsillectomy), were detected during the study. DNA sequencing revealed a heterozygote CGG to CAG (Arg364Gln) variant in exon 9 at nucleotide position 1091, consistent with the genetic variant of FVII Padua. Timely diagnosis of FVII Padua is vital to avoid unnecessary exposure of patients to replacement therapy.

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“…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 . The underlying mechanism for this striking variation in bleeding diathesis is not known.…”

Section: Introductionmentioning

confidence: 96%

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

2013

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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.

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Asymptomatic Factor VII Deficiency in African Americans

Cited by 12 publications

References 19 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

Factor VII Padua in Iran: clinical and laboratory findings of three unrelated patients

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

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