Factor VII congenital deficiency (FVII CD; 2017 ICD-10-CM: D68.2) is an autosomal recessive inherited bleeding disorder caused by reduced levels of coagulation factor (F) VII, a vitamin K-dependent serine protease with structural similarity to other coagulation enzymes, including FIX, FX and protein C.
The plasma concentration of FVII is decreased to a variable degree relative to the total FVII pool. Bleeding symptoms are not expected with FVII plasma values >25% of normal, but plasma concentrations do not correlate with bleeding symptoms and even individuals with values <3% can be asymptomatic. FVII deficiencies in asymptomatic individuals are detected by prolonged prothrombin time (PT). Depending on the reagent used, international normalised ratio (INR) values in FVII-deficient patients can vary significantly. Following tissue injury, extravascular tissue factor (TF) comes in contact with circulating FVII, which is thereby activated to FVIIa. Once activated, the TF-FVIIa complex acts as part of the extrinsic coagulation pathway to catalyse the activation of FIX and FX to FIXa and FXa, respectively, in the presence of phospholipids and calcium.1-4
FVII CD affects males and females equally and has a prevalence of approximately one in 500,000 births. The F7 gene that encodes FVII is located on chromosome 13, and FVII deficiency is occasionally observed in conjunction with nearby FX gene mutations that result in a concomitant FX deficiency.1-3
A heterogeneous range of gene polymorphisms and mutations associated with FVII CD have been characterised, however even homozygous or compound heterozygous patients with very severe phenotypes appear to have some residual enzymatic activity. Together with observations from animal models, this suggests that true null mutations may be lethal.2,3
Disease severity among patients with FVII CD is heterogeneous, ranging from a life-threatening bleeding diathesis to asymptomatic in the absence of trauma or invasive procedures. Common bleeding symptoms include epistaxis, haematomas, gum bleeding and haemarthrosis as well as life-threatening gastrointestinal or central nervous system bleeds in patients with more severe phenotypes. Menorrhagia among affected females is common. Surgery is often well tolerated, however many mild or asymptomatic patients are first diagnosed following trauma or invasive procedures.1-3
While low levels of FVII are generally associated with a more severe clinical bleeding phenotype, genotype alone is not consistently predictive of clinical phenotype, suggesting a contribution by other genetic or environmental factors.1-3
1. de Moerloose P, Schved JF, Nugent D. Rare coagulation disorders: fibrinogen, factor VII and factor XIII. Haemophilia 2016;22 Suppl 5:61-5.
2. Mariani G, Bernardi F. Factor VII deficiency. Semin Thromb Hemost 2009;35:400-6.
3. Lapecorella M, Mariani G, International Registry on Congenital Factor VIID. Factor VII deficiency: defining the clinical picture and optimizing therapeutic options. Haemophilia 2008;14:1170-5.
4. Amiral J, Dunois C, Amiral C, Seghatchian J. The various assays for measuring activity states of factor VIIa in plasma and therapeutic products: Diagnostic value and analytical usefulness in various pathophysiological states. Transfus Apher Sci 2017;56:91-7.
