Congenital factor X deficiency, an autosomal recessive disease, occurs in one per one million in the general population. As expected, it occurs more frequently in communities where consanguineous marriage is common [1]. The manifestations of factor X deficiency are not unlike those of other coagulation factors. It is the most severe among the rare congenital coagulopathies [2].

The sites of bleeding depend to some extent on the severity of the disease, which is correlated with the residual activity of factor X [1] [2]. Severe cases may present in the neonate with an umbilical stump bleeding 7-10 days after birth [2]. Other spontaneous bleeding incidents in severely affected patients are hemarthroses, gastrointestinal bleeding, central nervous system hemorrhages, and post-surgical hemorrhages. Women may have severe bleeding during periods and post-partum. They may also experience bleeding into the peritoneum from ruptured luteal cysts [3]. Patients with less severe deficiencies bruise more easily; menorrhagia and gum bleeding are also very common [2]. Nosebleeds occur with all degrees of deficiency [1].

Acquired deficiency of factor X is also rare, and most cases are associated with amyloidosis [4] [5]. Factor X is not the only coagulation factor affected by amyloidosis, but it is the most frequent. Liver disease and vitamin K deficiency also affect the activity of factor X as well as several other coagulation factors [2]. Various tumors, myeloma, respiratory virus infections, leprosy and certain medications [2] [6] are also associated with higher incidence of factor X deficiency.

Registries of patients of European, American, Asian Indian, and Iranian extraction with factor X deficiencies now exist [7] [8] [9] [10] [1]. With a cut-off value of less than 0.1 IU/ml for Factor X activity, bleeding episodes tend to be more severe, whereas above that value the symptoms are milder [11]. The most serious types of bleeding (gastrointestinal and intracranial bleeding, hemarthroses) occur at or below values of activity that are about five times lower than the cutoff value [7] [12].

• Pain

  We describe a case of primary amyloidosis (AL) with severe factor X (FX) deficiency in an amateur cyclist presenting with muscular pain at rest and ecchymoses in his legs. [ncbi.nlm.nih.gov]

  […] and back pain, according to the labeling. [ashp.org]

  Common adverse effects of plasma-derived Factor X include back pain, infusion site erythema, fatigue and infusion site pain. [mims.co.uk]

  In clinical studies, the most common adverse reactions (frequency ≥5% of subjects) with Coagadex were infusion site erythema, infusion site pain, fatigue and back pain. [prnewswire.com]

• Asymptomatic

  Heterozygote patients most often remain asymptomatic. Etiology Inherited congenital FX deficiency is caused by mutations in the F10 gene (13q34) controlling the production of plasma FX. [orpha.net]

  The patient recovered uneventfully and remained asymptomatic during the 1-year follow-up. [ncbi.nlm.nih.gov]

• Surgical Procedure

  Activated recombinant factor VII might be considered in patients undergoing major surgical procedures, but further experience is needed. [mayoclinic.pure.elsevier.com]

  To date, 34 of 102 patients have been treated for severe bleeding episodes or for surgical procedures. [ncbi.nlm.nih.gov]

  In a total of seven surgical procedures analysed, there was no post-operative bleeding and no requirement for blood transfusions. [mims.co.uk]

  If the patient had had other risk factors for thrombosis, or if he had undergone a less-invasive or less-risky surgical procedure, we likely would have used FFP instead. [academic.oup.com]

  Mild (> 40% activity): Patients are mostly asymptomatic, but might have problems with bleeding during trauma, a surgical procedure or with pregnancy/delivery Moderate (10-40% activity): Patients may have mild spontaneous bleeding, or bleeding triggered [rarebleedingdisorders.com]

• Easy Bruising

  The gene causing this condition is autosomal recessive; thus, only those inheriting from both parents exhibit clinical symptoms, such as moderate bleeding, easy bruising and subcutaneous bleeding from mucous membranes. [ncbi.nlm.nih.gov]

  Patients may experience severe umbilical cord stump bleeding, recurrent epistaxis, soft-tissue hemorrhages, menorrhagia, easy bruising, hematuria, hemarthroses and excessive bleeding during or following surgery or delivery or trauma. [orpha.net]

• Vomiting

  […] bleeding at birth (for those severely affected) Nose bleeds Mouth bleeds Easy bruising Swelling, pain, or warmth around a joint Inability to straighten or bend a joint normally Headache or neck ache Drowsiness or loss of consciousness Upset stomach Vomit [rarebleedingdisorders.com]

  Patient’s Analysis The first case was a 3-year-old boy who was referred to the hematology department of a general hospital in April 2009, due to the epistaxis, pallor, vomiting, and epileptic seizure. [ircmj.com]

  Migraine Headache Migraine headache is a type of headache associated with a sensitivity to light, smells, or sounds, eye pain, severe pounding on one side of the head, and sometimes nausea and vomiting. [medicinenet.com]

  […] probably following rupture of an ovarian cyst in a 25-year-old woman with FX deficiency carrier state (FX activity: 26%). » Case Report A 25-year-old, unmarried woman presented to emergency department with complaints of sudden onset severe abdominal pain, vomiting [ijccm.org]

  […] hemarthrosis), which may cause the following: Swelling Stiffness and pain Tingling sensation The joint may feel warm to touch Bleeding in the central nervous system, including the spinal cord and brain, which may cause: Headaches Seizures Numbness Nausea and vomiting [dovemed.com]

• Nausea

  Migraine Headache Migraine headache is a type of headache associated with a sensitivity to light, smells, or sounds, eye pain, severe pounding on one side of the head, and sometimes nausea and vomiting. [medicinenet.com]

  (hemarthrosis), which may cause the following: Swelling Stiffness and pain Tingling sensation The joint may feel warm to touch Bleeding in the central nervous system, including the spinal cord and brain, which may cause: Headaches Seizures Numbness Nausea [dovemed.com]

  People who are addicted to cocaine may experience symptoms of: Dilated pupils and hypersensitivity to light and sound Restlessness Increased heartbeat and respiration Nausea and stomach upset Problems with nosebleeds and loss of sense of smell, if snorted [sunrisehouse.com]

• Bleeding Gums

  [ more ] 0000421 Gingival bleeding Bleeding gums 0000225 Menorrhagia Abnormally heavy bleeding during menstruation 0000132 Persistent bleeding after trauma Excessive bleeding after minor trauma Frequent bleeding with trauma Prolonged bleeding after minor [rarediseases.info.nih.gov]

  In cases of severe factor V deficiency, the symptoms often include: abnormal bleeding after giving birth, having surgery, or being injured abnormal bleeding under the skin umbilical cord bleeding at birth nosebleeds bleeding gums easy bruising heavy or [healthline.com]

• Erythema

  Among the 18 patients with hereditary factor X deficiency who received at least one dose of the replacement therapy during either of its two clinical studies, the most common adverse reactions were infusion-site erythema, infusion-site pain, fatigue, [ashp.org]

  Common adverse effects of plasma-derived Factor X include back pain, infusion site erythema, fatigue and infusion site pain. [mims.co.uk]

  In clinical studies, the most common adverse reactions (frequency ≥5% of subjects) with Coagadex were infusion site erythema, infusion site pain, fatigue and back pain. [prnewswire.com]

  In clinical studies, the most common adverse reactions (frequency ≥5% of subjects) with COAGADEX were infusion site erythema, infusion site pain, fatigue and back pain. Please see complete Prescribing Information for COAGADEX. References: 1. [coagadex.com]

• Back Pain

  […] and back pain, according to the labeling. [ashp.org]

  Common adverse effects of plasma-derived Factor X include back pain, infusion site erythema, fatigue and infusion site pain. [mims.co.uk]

  In clinical studies, the most common adverse reactions (frequency ≥5% of subjects) with Coagadex were infusion site erythema, infusion site pain, fatigue and back pain. [prnewswire.com]

  In clinical studies, the most common adverse reactions (frequency ≥5% of subjects) with COAGADEX were infusion site erythema, infusion site pain, fatigue and back pain. Please see complete Prescribing Information for COAGADEX. References: 1. [coagadex.com]

• Lethargy

  I Deficiency Disease (Ornithine Carbamoyl Phosphate Deficiency) Carbamyl-Phosphate Synthetase I Deficiency Disease Hyperammonemia Due to Carbamoyl Phosphate Synthetase 1 Deficiency Scope note in EnglishA urea cycle disorder manifesting in infancy as lethargy [arl4.library.sk]

  […] suicide attempt, suicide ideation CNS effects most commonly reported (in greater than 1% of patients) were: feeling abnormal, balance disorder, feeling drunk, disturbance in attention, dizziness, somnolence, disorientation, dissociation, dysarthria, lethargy [glosbe.com]

Bleeding episodes in a patient will prompt the usage of the standard hemostasis tests: the prothrombin time (PT) - together with the derived international normalized ratio (INR), - and the activated partial thromboplastin time (APTT). Factor X deficiency usually results in prolonged PT, APTT, as well as in a prolonged Russell viper venom time (RVVT) in which the viper venom activates Factor X [2] [13], and therefore directly tests factor X. The bleeding time and thrombin time are normal in Factor X deficiencies.

There are also tests for factor X activity, which is determined by one stage PT-based assay. The factor X protein (FX antigen) can be measured by immunological methods [2]. One classification scheme for the disease involves the relationship of these last two measurements: In type I deficiency the levels of both enzyme activity and protein (antigen) are low, whereas severely depressed activity despite near normal antigen levels is type II deficiency [2] [7] [14].

Acquired deficiency of factor X occurs in about ten percent of immunoglobulin light chain (AL)-amyloidosis patients. Mixing tests may reveal if there is an immunologic origin of factor X deficiency. Liver disease and coumarin anticoagulant administration can cause factor X deficiency, together with deficiencies in other coagulation factors.

Management and treatment Prothrombin Complex Concentrates (PCCs) or fresh frozen plasma (if PCCs are not available) is usually used to treat hemorrhagic episodes. Prognosis Prognosis is good with correct diagnosis and adequate treatment. [orpha.net]

He rates his quality of life improved since starting prophylactic treatment. There have been no thrombotic events. [ncbi.nlm.nih.gov]

Systemic AL amyloidosis with acquired factor X deficiency: A study of perioperative bleeding risk and treatment outcomes in 60 patients. [mayoclinic.pure.elsevier.com]

[…] evaluation and treatment of the patients with AL amyloidosis. [ashpublications.org]

Prognosis Prognosis is good with correct diagnosis and adequate treatment. The documents contained in this web site are presented for information purposes only. [orpha.net]

The prognosis is poor and the median survival is 13 months. Bleeding problems resulting from coagulopathy frequently complicates systemic amyloidosis. [ncbi.nlm.nih.gov]

Etiology Inherited congenital FX deficiency is caused by mutations in the F10 gene (13q34) controlling the production of plasma FX. The severity of the bleeding manifestations correlates with the FX level. [orpha.net]

This practical text covers disorders of thrombosis and hemostasis in a logical and sequential manner: etiology, pathophysiology, clinical and laboratory diagnosis, and management. [books.google.com]

His history and medical workup were negative for an acquired etiology, and genetic testing confirmed a hereditary etiology of factor X deficiency. [hindawi.com]

Additional in silico analyses indicated these mutations’ putative pathogenic involvement in the etiology of FXD. “The identification of 11 novel mutations provides a substantial contribution to the mutations known to cause FXD,” the authors wrote. [hematologyadvisor.com]

Summary Epidemiology Prevalence of homozygous forms is estimated at 1/500,000. Both sexes are equally affected. Clinical description Congenital FX deficiency manifests at any age but in general, severe forms of the disease manifest early in life. [orpha.net]

Terminology Also known as Stuart-Prower Factor Deficiency Deficiency classified as either: Type I: decreased functional activity and antigen level (quantitative defect) Type II: decreased functional activity and near normal antigen level (qualitative defect) Epidemiology [pathologyoutlines.com]

Genatlas disease for F10 Gene bleeding diathesis (FX deficiency) Relevant External Links for F10 Genetic Association Database (GAD) F10 Human Genome Epidemiology (HuGE) Navigator F10 Atlas of Genetics and Cytogenetics in Oncology and Haematology: F10 [genecards.org]

The clinical and pathophysiological aspects of this case are discussed based on a literature review. [ncbi.nlm.nih.gov]

This practical text covers disorders of thrombosis and hemostasis in a logical and sequential manner: etiology, pathophysiology, clinical and laboratory diagnosis, and management. [books.google.com]

[…] provide information on better ways of managing the replacement therapy in patients with similar mutations. a Department of Neuroscience, Psychology, Drug Research and Child Health, Careggi University Hospital of Florence, Florence, Italy b Department of Pathophysiology [journals.lww.com]

The pathophysiology of this deficiency is thought to be adsorption of factor X onto tissue amyloid fibrils therefore reducing the level of functional factor X in the circulation. [helena-biosciences.com]

Iran), incidence is reported to be 1 in 200,000 Estimated carrier incidence of 1 in 500 Sites Bleeding into skin and mucosa, joint and muscle, genitourinary tract, gastrointestinal tract, CNS (see clinical features below) Pathophysiology Factor X is a [pathologyoutlines.com]

However, had he been diagnosed earlier pre-operatively, the post-operative complication could have been prevented. [ncbi.nlm.nih.gov]

Factor X deficiency, an inherited disorder, prevents the blood from clotting as it should. Individuals with the condition typically are treated with fresh-frozen plasma or plasma-derived prothrombin complex concentrates to stop or prevent bleeding. [healio.com]

There is no known prevention for inherited factor X deficiency. When a lack of vitamin K is the cause, using vitamin K can help. Gailani D, Wheeler AP, Neff AT. Rare coagulation factor deficiencies. [nlm.nih.gov]

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2. Uprichard J, Perry DJ. Factor X Deficiency. Blood Rev. 2002;16:97-110.
3. Dafopoulos K, Galazios G, Georgadakis G, et al. Two episodes of hemoperitoneum from luteal cyst rupture in a patient with congenital factor X deficiency. Gynecol Obstet Invest. 2003;55(2):114-115.
4. Enjeti AK, Walsh M, Seldon M. Spontaneous major bleeding in acquired factor X deficiency secondary to AL-Amyloidosis. Haemophilia. 2005;11(5):535-538.
5. Takabe K, Holman PR, Herbst KD, Glass CA, Bouvet M. Successful perioperative management of factor X deficiency associated with primary amyloidosis. J Gastrointest Surg. 2004;8(3):358-362.
6. Lee G, Duan-Porter W, Metjian AD. Acquired, non-amyloid related factor X deficiency: review of the literature. Haemophilia. 2012 Sep;18(5):655-63.
7. Herrmann FH, Auerswald G, Ruiz-Saez A, et al. Factor X deficiency: clinical manifestation of 102 subjects from Europe and Latin America with mutations in the factor 10 gene. Haemophilia. 2006;12(5):479-489.
8. Acharya SS, Coughlin A, Dimichele DM, North American Rare Bleeding Disorder Study G. Rare Bleeding Disorder Registry: deficiencies of factors II, V, VII, X, XIII, fibrinogen and dysfibrinogenemias. J Thromb Haemost. 2004;2:248-256.
9. Peyvandi F, Mannucci PM. Rare coagulation disorders. Thromb Haemost. 1999 Oct;82(4):1207-1214.
10. Viswabandya A, Baidya S, Nair SC, et al. Correlating clinical manifestations with factor levels in rare bleeding disorders: a report from Southern India. Haemophilia. 2012;18:e195-200.
11. Mumford AD, Ackroyd S, Alikhan R, et al, for the BCSH Committee. Guideline for the diagnosis and management of the rare coagulation disorders: a United Kingdom Haemophilia Centre Doctors' Organization guideline on behalf of the British Committee for Standards in Haematology. Br J Haematol. 2014 Nov;167(3):304-326.
12. Rauch R, Girisch M, Wiegand G, et al. Factor X deficiency and intracranial bleeding: who is at risk? Haemophilia. 2011;17:759-763.
13. Hertzberg M. Biochemistry of factor X. Blood Rev. 1994 Mar;8(1):56-62.
14. Girolami A, Vettore S, Scarparo P, Lombardi AM. Persistent validity of a classification of congenital factor X defects based on clotting, chromogenic and immunological assays even in the molecular biology era. Haemophilia. 2011;17:17-20.