Factor X deficiency

Factor X, a vitamin K-dependent plasma glycoprotein, plays a pivotal role in the coagulation cascade, being the first enzyme in the common pathway of thrombin formation. Congenital factor X deficiency is very rare and among the most severe hereditary coagulation defects. Bleeding manifestations typically include haemarthroses, muscle haematomas, umbilical cord bleeding, and gastrointestinal and central nervous system (CNS) bleeding. Age of onset is variable: severe forms typically present from the neonatal period through childhood, whereas milder forms may remain undetected until adulthood. The clinical manifestations and laboratory phenotypes of factor X deficiency are poorly correlated; therefore, individuals with mild or moderate disease may still experience clinically significant bleeding.

The estimated prevalence is 1/500,000-1/1,000,000.

Hereditary factor X deficiency is caused by biallelic germline pathogenic variants in F10. Pathogenic F10 variants either reduce coagulant activity in concordance with antigen levels (type I) or impair function with preserved antigen (type II), disrupting common-pathway thrombin generation, resulting in bleeding diathesis.

Factor X deficiency is inherited in an autosomal recessive manner. Both parents of an affected individual are typically obligate heterozygous carriers, and the recurrence risk for each subsequent pregnancy is 25%. Heterozygous carriers are generally asymptomatic. Prenatal molecular testing is technically possible once the familial pathogenic variant has been identified.

Diagnosis is established by a concomitant prolongation of the prothrombin time (PT) and activated partial thromboplastin time (aPTT), combined with a low level of factor X coagulant activity. The diagnosis may be confirmed by molecular genetic analysis of the F10 gene.

• Establishing the diagnosis: a confirmed molecular cause clarifies the clinical picture and supports diagnostic certainty.
• Family member testing: knowledge of the familial pathogenic variant enables predictive and carrier testing in at-risk relatives.

• Karimi M, Menegatti M, Afrasiabi A, Sarikhani S, Peyvandi F. Phenotype and genotype report on homozygous and heterozygous patients with congenital factor X deficiency. Haematologica. 2008 Jun;93(6):934-8. doi: 10.3324/haematol.12211. Epub 2008 Apr 9. PMID: .
• 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
• Chitlur M, Amos LE, Reding MT, Sabo C, Acharya S. Characterization and management of patients with hereditary factor X deficiency: A case series. Transfusion. 2025;65(10):1786-1792. doi: 10.1111/trf.18377. PMID: . PMCID: PMC12531909.