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

Abstract

 

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.