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Factor X Deficiency

Factor X is the first enzyme in the final, common part of the coagulation pathway; its activity is vitamin-K dependent. Congenital factor X deficiency is extremely rare, but some patients are severely affected. Factor X deficiency can also be acquired; it can be associated with several conditions, among them malignancies, but acquired deficiency most often occurs in patients with amyloidosis.


Presentation

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].

Intravenous Administration
  • Changes in plasma prothrombin, A-c globulin and antithrombin concentration following intravenous administration of estrogen. Proc Soc exp Biol Med 1957; 94: 92-4. 9. McGovern JJ, Bunker JP, Goldstein R, Estes J W.[afjho.com]
Easy Bruising
  • 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]
  • 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]
Diarrhea
  • Neither proteinuria nor diarrhea was observed as an initial manifestation. Although a bone marrow examination revealed direct fast scarlet-positive extracellular deposits, they did not exhibit red-to-green dichroism under polarized light.[ncbi.nlm.nih.gov]
Mitral Valve Prolapse
  • In addition, her mother had elevated plasma cholesterol levels, and her father primary hypercholesterolemia as well as mitral valve prolapse. The twin sister, heterozygous for factor X deficiency, displayed mitral valve prolapse.[ncbi.nlm.nih.gov]
Bleeding Gums
  • 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]
Skin Bleeding
  • Factor X deficiency commonly causes nosebleeds, easy bruising, bleeding under the skin, bleeding of the gums, blood in the urine (hematuria), and prolonged or excessive bleeding following surgery or trauma.[ghr.nlm.nih.gov]
Convulsions
  • Our case an 18-year-female with known Factor X deficiency with menorrhagia developed severe hypertension, followed by generalised tonic clonic convulsions apparently after blood component transfusion.[ncbi.nlm.nih.gov]
Encephalopathy
  • Adverse neurological transfusion reactions including posterior reversible encephalopathy syndrome (PRES) following blood transfusion are rare.[ncbi.nlm.nih.gov]

Workup

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.

Hypercholesterolemia
  • While the proband demonstrated factor X deficiency, obstructive hypertrophic cardiomyopathy, and primary hypercholesterolemia, her parents and her elder sister were considered heterozygous for factor X.[ncbi.nlm.nih.gov]

Treatment

  • 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]

Prognosis

  • 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]
  • Bleeding-Disorders/Types-of-Bleeding-Disorders/Other-Factor-Deficiencies National Hemophilia Foundation: Victory for Women with Blood Disorders -- www.hemophilia.org/Community-Resources/Women-with-Bleeding-Disorders/Victory-for-Women-with-Blood-Disorders Outlook (Prognosis[ufhealth.org]
  • Neonatal subgaleal hemorrhage: clinical presentation, treatment, and predictors of poor prognosis . Pediatr Int 2007; 49 (6): 903–907. 3. Doumouchtsis SK , Arulkumaran S . Head trauma after instrumental births .[nature.com]

Etiology

  • 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]
  • […] first enzyme in the common pathway to form a fibrin clot Its activated form (in complex with factor Va, Ca and phospholipid) cleaves prothrombin to thrombin It has a long half-life of 20 - 40 hours Images hosted on other servers: Coagulation cascade Etiology[pathologyoutlines.com]
  • „Molecular etiology of factor VIII deficiency in hemophilia A”. Hum. Mutat. 5 (1): 1—22. PMID 7728145. doi : 10.1002/humu.1380050102. Lenting PJ, van Mourik JA, Mertens K (1999).[sr.wikipedia.org]

Epidemiology

  • 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]
  • […] association with the following: Mycoplasma pneumoniae infection [33] Lupus anticoagulant [34] Sodium valproate administration [35] Upper respiratory tract infection [36] Leprosy [37] Severe burns in a child [38] Topical thrombin administration [39] Epidemiology[emedicine.medscape.com]
Sex distribution
Age distribution

Pathophysiology

  • 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]

Prevention

  • However, had he been diagnosed earlier pre-operatively, the post-operative complication could have been prevented.[ncbi.nlm.nih.gov]
  • Acquired factor X deficiency can also be caused by certain drugs such as medicines that prevent clotting, or by a deficiency of vitamin K.[ghr.nlm.nih.gov]
  • 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]

References

Article

  1. Peyvandi F, Mannucci PM, Lak M, et al. Congenital factor X deficiency: spectrum of bleeding symptoms in 32 Iranian patients. Br J Haematol. 1998;102:626-628.
  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.

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Last updated: 2019-07-11 21:20