Factor VII Deficiency: From Basics to Clinical Laboratory Diagnosis and Patient Management

Abstract

Factor VII (FVII) deficiency is a rare inheritable bleeding disorder affecting 1/500 000 individuals. Clinical manifestations are heterogeneous, from asymptomatic to severe and potentially fatal bleeding. These clinical manifestations do not correlate well with FVII plasma levels. For this reason, FVII-deficient patient management during surgery or for long-term prophylaxis remains challenging. Laboratory testing for FVII activity is, however, the first-line method for FVII deficiency diagnosis and is helpful for managing patients in combination with clinical history. Additional testing consists of FVII immunoassay and genetic testing. Genetic abnormalities on the FVII gene are heterogeneous and can translate into quantitative or qualitative defects. Some of the latter can react differently with different thromboplastins; this can be misleading for the laboratory as no consensus exists at present on an FVII deficiency diagnosis methodology. Indeed, no single test is able to predict accurately the bleeding risk. This review provides a broad picture of inherited and acquired FVII deficiency with a particular focus on laboratory diagnosis.

Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy

“…The Padua variant of FVII deficiency (Arg304Gln in exon 8) shows a different reactivity toward different tissue thromboplastins and determines normal results when brain thromboplastin is employed [31]. On the contrary, type I defect has never been reported to display variable reactivity toward different thromboplastins [32]. …”

Severe Ulcerative Colitis Flare Unmasking Factor VII Deficiency

“…It can be divided into Type I and Type II, which reflects quantitative and qualitative defect respectively (Sevenet et al 2016). Bleeding in factor VII deficiency typically presents in locations more dependent on the extrinsic pathway including the brain, bowel, uterus, placenta, lungs, and heart (Lapecorella & Mariani 2008).…”

Factor VII Gene Defects: Review of Functional Studies and Their Clinical Implications

“…The deficiency of FVII was first described in 1951. The disease is known as a hereditary bleeding disorder with prevalence of 1 in every 300,000-500,000 individuals [7,26] . Children with congenital Upon contact with tissue factor exposed by vascular injury, FVII is cleaved into its two-chain active form (FVIIa), mainly by factor Xa.…”

“…Patients with severe FVII deficiency may experience joint and muscle bleeding, easy bruising, and postoperative hemorrhage. Bleeding can also occur spontaneously in the mouth, the nose, the genitals, and urinary tract [26] . Furthermore, the affected women often suffer from severe menorrhagia [29] .…”

“…On the other hand, many patients with a specific mutation in the F7 gene may have no significant clinical manifestation. Currently, comprehensive information regarding these mutations is available at the FVII gene variants database (http://www.factorvii.org) [26] . Point mutations are the main causes of FVII inherited defects, where missense mutations are the most frequent variants.…”