Factor VII deficiency: clinical manifestation of 717 subjects from Europe and Latin America with mutations in the factor 7 gene

Abstract

The congenital FVII deficiency (FVIID) is a rare haemorrhagic disorder with an autosomal recessive pattern of inheritance. Data on phenotype and the genotype from 717 subjects in Central Europe (six countries), Latin America (Costa Rica, Venezuela) and United States, enrolled in the Greifswald Registry of FVII Deficiency were analysed. We detected 131 different mutations in 73 homozygous, 145 compound heterozygous and 499 heterozygous subjects. Regional differences were observed in the mutation pattern and the clinical profile of the evaluated patients. Seventy-one per cent of homozygous and 50% of compound heterozygous subjects were symptomatic. The clinical manifestations of the homozygous subjects were characterized by intracranial haemorrhage (2%), gastrointestinal bleeding (17%), haemarthrosis (13%), epistaxis (58%), gum bleeding (38%), easy bruising (37%), haematoma (15%), haematuria (10%) and menorrhagia (19 of 26 females, 73%). The clinical variability and genotype-phenotype correlation was evaluated in the homozygous subjects. The pattern of bleeding symptoms among compound heterozygous patients was severe and similar to that of the homozygous patients. The large-scale analysis of 499 heterozygous subjects shows that 93 (19%) presented with spontaneous bleeding symptoms such as haemarthrosis (4%), epistaxis (54%), gum bleeding (14%), easy bruising (38%), haematoma (23%), haematuria (5%) and menorrhagia (19 of 45 females; 42%). The severe haemorrhages - intracranial and gastrointestinal - were not reported in heterozygous subjects. The clinical variability and the regional differences in the mutation pattern are discussed regarding care and treatment.

Ox Brain versus Rabbit Brain Thromboplastin Assays Are the Best Tool for a Preliminary Diagnosis of the Arg304Gln Factor VII Defect (FVII Padua)

“…The condition is rare but it is the most frequent condition among the rare coagulation disorders [2,3,4]. …”

Recombinant, activated factor VII for surgery in factor VII deficiency: a prospective evaluation – the surgical STER

“…Treatment demands vary considerably amongst FVIIdeficient patients, ranging from none or rare on-demand treatment to frequent factor administration required for longterm or short-term prophylaxis, such as for major surgical interventions (Mariani et al 2003Herrmann Wulff et al, 2009). The variability of RT requirement depends, in part, on the clinical and clotting severity of the defect, but in surgery other elements should be taken into account for the assessment of bleeding risk, such as type of surgery, tissue/organ involved, and type of anaesthesia.…”

“…Factor VII (FVII) deficiency is a CBD with an estimated prevalence of 1/500 000 individuals (Mannucci et al, 2004) without ethnic or gender predilection (Perry, 2002;, Roberts & Escobar, 2006Herrmann Wulff et al, 2009. Treatment demands vary considerably amongst FVIIdeficient patients, ranging from none or rare on-demand treatment to frequent factor administration required for longterm or short-term prophylaxis, such as for major surgical interventions (Mariani et al 2003Herrmann Wulff et al, 2009).…”

Management of Arthropathy in Moderately Deficient Factor VII Patients: Results From Hospital Developed Treatment Protocol

“…In India, the epidemiological data on factor VII (FVII) disorder are scarce. FVII activity levels are poorly correlated with hemorrhagic manifestation in individuals [3,4]. Serious arthropathy is observed in cases which are severely affected with spontaneous bleeding and hemarthrosis.…”