The bleeding tendency may appear at any age, although the more severely affected patients (FX activity <1%) present early in life with, for instance, umbilical-stump or central nervous system (CNS) bleeding (PMID:19598069).
Factor X deficiency is a rare autosomal recessive bleeding disorder showing variable phenotypic severity. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. The disorder can be caused either by reduced levels of ... Factor X deficiency is a rare autosomal recessive bleeding disorder showing variable phenotypic severity. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. The disorder can be caused either by reduced levels of the factor X protein or by synthesis of a dysfunctional factor X protein (summary by Millar et al., 2000).
Girolami et al. (1970) described a congenital haemorrhagic condition due to the presence of an abnormal factor X in a large kindred from Friuli, a remote valley in northeastern Italy. Girolami et al. (1971) reported another family from ... Girolami et al. (1970) described a congenital haemorrhagic condition due to the presence of an abnormal factor X in a large kindred from Friuli, a remote valley in northeastern Italy. Girolami et al. (1971) reported another family from Friuli with a bleeding disorder due to an abnormal factor X. The proposita was a 43-year-old woman with a history of bleeding since early childhood. She had had epistaxis, menorrhagia, bleeding after tooth extractions, gum bleeding, postpartum hemorrhage, posttraumatic hemarthroses, and hematuria. Laboratory studies showed prolonged prothrombin time (PT), prolonged partial thromboplastin time (PTT), and correction with Russell viper venom. Factor X activity was significantly decreased (6 to 9% of normal), but antigen levels were normal; however, an abnormal factor X protein was identified immunologically, indicating a qualitative deficiency. The patient's 2 children and mother had 38 to 48% activity levels, consistent with the heterozygous state. Sumer et al. (1986) reported a Saudi Arabian infant with severe factor X deficiency who had had 2 intracranial hemorrhages. De Stefano et al. (1988) reported a 13-year-old girl, born of consanguineous parents, with defective factor X. Laboratory studies showed normal factor X antigen levels, but the protein was severely impaired in activation via the intrinsic pathway (3% of normal) and partially defective in activation via the extrinsic pathway (30-50% of normal). The variant protein, termed factor X Roma, was activated by Russell viper venom. The parents of the proposita showed factor X functional levels compatible with heterozygosity for the abnormality. Millar et al. (2000) determined that the Roma variant results from a T318M substitution (613872.0015) in the F10 gene. Peyvandi et al. (1998) studied 32 Iranian patients with congenital factor X deficiency. The most frequent symptom was epistaxis, which occurred in 72% of patients, with all degrees of deficiency. Other mucosal hemorrhages (e.g., hematuria, gastrointestinal bleeding) were less frequent and occurred mainly in patients with unmeasurable factor X. Menorrhagia occurred in half of the women of reproductive age. Soft tissue bleeding occurred in two-thirds of the patients; spontaneous hematomas and hemarthoses led to severe arthropathy in 5 patients. Bleeding from the umbilical stump was an unexpected finding in 9 patients. The study demonstrated that the bleeding tendency of factor X deficiency can be severe and correlates with factor levels. - Acquired Factor X Deficiency Furie et al. (1977) presented evidence that the acquired deficiency of factor X associated with systemic amyloidosis is caused by binding of the factor X protein to amyloid. Ashrani et al. (2003) described factor X deficiency associated with lupus anticoagulant and a bleeding diathesis. They reported 2 patients in whom severe bleeding developed after a respiratory infection. Both the factor X deficiency and lupus anticoagulant were transient. Deficiency of factor X may be another mechanism whereby patients with antiphospholipid antibodies present with bleeding complications.
In a patient with a bleeding disorder due to factor X deficiency, Reddy et al. (1989) identified compound heterozygosity for 2 mutations in the F10 gene (613872.0001 and 613872.0002). The patient had prolonged bleeding after surgery, and laboratory ... In a patient with a bleeding disorder due to factor X deficiency, Reddy et al. (1989) identified compound heterozygosity for 2 mutations in the F10 gene (613872.0001 and 613872.0002). The patient had prolonged bleeding after surgery, and laboratory studies showed that factor X activity and antigen were 14% and 36% of normal, respectively. This was the first characterization of factor X deficiency at the molecular level. Bernardi et al. (1989) found that a patient with factor X deficiency was a genetic compound for 2 mutations affecting the F10 gene: the maternal allele contained a partially deleted gene missing the 3-prime portion coding for the catalytic domain of the factor; the defect on the paternal F10 allele was not determined. James et al. (1991) demonstrated that factor X Friuli is caused by a homozygous mutation in the F10 gene (P343S; 613872.0004). Wieland et al. (1991) identified an instance of germline mosaicism for deletion of exons 7 and 8 of factor X. One offspring had this deletion and a different deletion inherited from the mother, i.e., she was a compound heterozygote. Millar et al. (2000) sequenced the F10 genes of 14 unrelated individuals with factor X deficiency, including 12 familial and 2 sporadic cases, and found a total of 13 novel mutations (see, e.g., 613872.0012-612872.0014). Missense mutations were studied by means of molecular modeling, whereas single basepair substitutions in splice sites and the 5-prime flanking region were examined by in vitro splicing assay and luciferase reporter gene assay, respectively. The deletion allele of a novel 6-nucleotide insertion/deletion polymorphism in the F10 gene promoter region was shown by reporter gene assay to reduce promoter activity by approximately 20%. Variation in the antigen level of heterozygous relatives of probands was found to be significantly higher between families than within families, consistent with the view that the nature of the F10 lesion(s) segregating in a given family is a prime determinant of the laboratory phenotype. Millar et al. (2000) commented that the complete absence of nonsense mutations in the F10 mutational spectrum is highly unusual. The ratio of nonsense to missense mutations is normally approximately 1 in 4. The observed lack of nonsense mutations was statistically significant. Assuming that the relative rate of single basepair substitutions in the F10 gene is similar to the overall mutational spectrum of human genes, this discrepancy would be explicable only in terms of a reduced relative likelihoods of clinical observation (RCOL; Krawczak et al., 1998) of nonsense versus missense mutations as compared with other genes. The reasons for this reduction were not clear. Peyvandi et al. (2002) analyzed the phenotype and genotype of 15 Iranian patients with factor X deficiency from 13 unrelated families with a high frequency of consanguinity. Nine different homozygous candidate mutations were identified, of which 8 were novel.