Factor VII deficiency

Congenital factor VII deficiency presents with a highly heterogeneous bleeding phenotype. Clinically, it affects multiple haemorrhage-prone organ systems and varies markedly in severity between affected individuals.

Mild and moderate forms are often asymptomatic and may come to attention only on routine coagulation testing, before surgery, or during the peripartum period. When bleeding is symptomatic, mucocutaneous manifestations predominate, including recurrent epistaxis, gum bleeding, easy bruising, and menorrhagia in affected women.

Severe forms can present already in the neonatal period with spontaneous intracranial or umbilical-stump haemorrhage, and the spectrum may extend to gastrointestinal haemorrhage, haemarthroses, and intramuscular haematomas resembling severe haemophilia. Onset thus ranges from life-threatening neonatal bleeding to incidental adult laboratory diagnosis.

Bleeding severity does not necessarily show a strong correlation with the underlying F7 gene variant or the residual factor VII activity. However, individuals with activity levels above 30% are usually free of symptoms. Only about 20% of patients with a single heterozygous variant present with spontaneous bleeding symptoms. The most severe types of bleeding, intracranial and gastrointestinal, do not normally occur in these patients.

The estimated prevalence of the recessive form is 1/500,000.

Congenital factor VII deficiency results from germline pathogenic variants in F7. The F7 gene maps to chromosome 13q34 and encodes coagulation factor VII, a vitamin K-dependent serine protease zymogen synthesised in the liver and released into the bloodstream. Factor VII is involved in the activation of and factor IX, which ultimately leads to fibrin polymerisation as the coagulation cascade progresses.

Congenital factor VII deficiency is inherited in an autosomal recessive manner. Heterozygous carriers are generally asymptomatic but may also exhibit symptoms of haemorrhagic diathesis. In addition to rare pathogenic variants, several functional polymorphisms have been identified in the promoter region of the F7 gene; these occur at a relatively high frequency and significantly influence serum levels of factor VII. 

Diagnosis rests on demonstrating reduced plasma factor VII coagulant activity. Initial coagulation screening typically shows isolated prolongation of the prothrombin time (PT) with a normal activated partial thromboplastin time (aPTT); confirmation requires a specific factor VII coagulant activity (FVII:C) assay, supported where indicated by molecular analysis of the F7 gene.

• Confirming the molecular diagnosis allows the clinical picture to be securely attributed to a defined genetic cause, with implications for prognosis and family counselling.
• Once the familial pathogenic variants are known, at-risk relatives can undergo predictive molecular testing to clarify their personal carrier status and inform reproductive and family-planning decisions.

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• Halimeh S, Koch L, Kenet G, Kuta P, Rahmfeld T, Stoll M, et al. Genotype-phenotype relationship among 785 unrelated White women with inherited congenital factor VII deficiency: a three-center database study. J Clin Med. 2023;13(1):49. doi:10.3390/jcm13010049. PMID: . PMCID: PMC10779797.
• Tourbih H, Harrach A, Bencharef H, Dehbi H, Oukkache B. Molecular aspects of rare coagulation factor deficiencies. Cureus. 2025;17(7):e89102. doi:10.7759/cureus.89102. PMID: . PMCID: PMC12311556.
• Herrmann FH, Wulff K, Auerswald G, Schulman S, Astermark J, Batorova A, et al.; Greifswald Factor FVII Deficiency Study Group. Factor VII deficiency: clinical manifestation of 717 subjects from Europe and Latin America with mutations in the factor 7 gene. Haemophilia. 2009;15(1):267-280. doi:10.1111/j.1365-2516.2008.01910.x. PMID: .