title: Factor VII deficiency: defining the clinical picture and optimizing therapeutic options.
abstract: Factor VII (FVII) deficiency is the most frequent among rare congenital bleeding disorders, accounting for one symptomatic individual per 500,000 population, apparently without any racial/ethnic predilection. FVII deficiency prevalence in the general population is probably higher because of the presence of asymptomatic and poorly symptomatic individuals. In accordance with the role of FVII as part of the initiating complex of the extrinsic coagulation pathway, laboratory diagnosis is easy, because FVII deficiency is the only congenital bleeding disorder characterized by isolated prolonged prothrombin time. Molecular diagnosis is available, and a broad spectrum of mutations has been characterized in the FVII gene, which is located in chromosome 13. Clinical manifestations are heterogeneous, ranging from severe life-threatening haemorrhages, such as cerebral, gastrointestinal, and joint haemorrhages, to miscellaneous minor bleeding. The main clinical features in our database (International Registry on Congenital FVII Deficiency database, n = 515) are as follows: (i) the absence of a clear-cut and consistent correlation between bleeding symptoms and FVII clotting levels; (ii) an excess of symptomatic women compared with men; (iii) frequent surgery-related bleeding, which is often a diagnostic tool in previously asymptomatic individuals. Several therapeutic options are possible, including plasma-derived and recombinant products, but therapeutic schedules, optimal dosages, and administration times still have to be precisely defined, and clinical studies, including online registries such as the Seven Treatment Evaluation Registry, are actually ongoing to achieve in a better manner a safe, rational and standardized substitution treatment for this congenital disorder.
authors.affiliation: Centro Emofilia e Trombosi, Unità Operativa Medicina Interna 2-Ematologia, Università de L'Aquila, Ospedale San Salvatore, Coppito, L'Aquila, Italy. emofilia.aq@cc.univaq.it
authors.forename: M
authors.initials: M
authors.lastname: Lapecorella
authors.forename: G
authors.initials: G
authors.lastname: Mariani
mesh_terms: D000367:Age Factors; D001777:Blood Coagulation / Q000502:physiology; D003029:Coagulants / Q000627:therapeutic use; D005167:Factor VII / Q000502:physiology*; D005168:Factor VII Deficiency / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D015942:Factor VIIa / Q000627:therapeutic use; D005260:Female; D006470:Hemorrhage / Q000188:drug therapy / Q000209:etiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D011247:Pregnancy; D011517:Prothrombin Time; D016032:Randomized Controlled Trials as Topic; D035583:Rare Diseases; D011994:Recombinant Proteins / Q000627:therapeutic use; D012042:Registries; D012720:Severity of Illness Index
chemical_list: D003029:Coagulants; D011994:Recombinant Proteins; D005167:Factor VII; C103587:recombinant FVIIa; D015942:Factor VIIa