Factor X congenital deficiency (FX CD; 2019 ICD-10-CM: D68.2) is a rare autosomal recessive bleeding disorder with an estimated prevalence of 1:1,000,000–1,500,000 population, irrespective of sex. FX plays a key role in the coagulation cascade, during which FX is activated by FIX (intrinsic pathway) or by tissue factor and activated FVII (extrinsic pathway). Active FX (FXa), in the presence of activated FV and Ca2+, cleaves prothrombin, converting it to active thrombin. Thus, defects in FX affect both the intrinsic and extrinsic clotting pathways.1,2
FX CD is classified into two categories, depending upon residual FX quantity and activity. Patients with type I FX CD exhibit low FX quantity and FX activity (usually <10% of FX activity for homozygotes), while patients with type II FX CD have decreased FX activity despite normal FX protein levels.1,3
Mutations that cause FX CD are largely missense mutations in the F10 gene located on chromosome 13. Genotyping of 105 different mutations showed that most families with FX CD carry a unique mutation. Patients with severe FX CD have a FX activity of <10% FX activity and severe bleeding phenotypes. However, patients with >10% FX activity often have mild to moderate bleeding phenotype and a lower likelihood of dangerous bleeding episodes.1
As with most rare bleeding disorders, symptoms of FX CD can range in severity depending on penetrance of the individual mutation. Patients with severe FX CD, defined by <10% FX activity, often present in infancy with umbilical stump bleeding and a severe bleeding phenotype and can be at a high risk for spontaneous bleeding. Patients with >10% FX activity often exhibit a milder phenotype with minor spontaneous bleeding and initial symptoms presenting at any age.
Classification of FX CD according to clotting factor levels4
Symptoms of FX CD are common to other coagulation bleeding disorders and include spontaneous bleeding, epistaxis, haematomas, haemarthrosis, menorrhagia, haematuria, bleeding after haemostatic challenge, and in severe cases, gastrointestinal and central nervous system bleeding. Persons who are heterozygous for FX (40-60% FX activity) may also have a mild bleeding phenotype and abnormality in clotting tests.1,2,4
1. Menegatti M, Peyvandi F. Factor X deficiency. Semin Thromb Hemost 2009;35:407-15.
2. Girolami A, Cosi E, Sambado L, Girolami B, Randi ML. Complex history of the discovery and characterization of congenital factor X deficiency. Semin Thromb Hemost 2015;41:359-65.
3. Girolami A, Scarparo P, Scandellari R, Allemand E. Congenital factor X deficiencies with a defect only or predominantly in the extrinsic or in the intrinsic system: a critical evaluation. Am J Hematol 2008;83:668-71.
4. Peyvandi F, Di Michele D, Bolton-Maggs PH, et al. Classification of rare bleeding disorders (RBDs) based on the association between coagulant factor activity and clinical bleeding severity. J Thromb Haemost 2012;10:1938-43.