Factor X DeficiencyNORD gratefully acknowledges Flora Peyvandi, MD, Associate Professor of Internal Medicine, Director of Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico and Department of Internal Medicine, University of Milan, for assistance in the preparation of this report. Show Synonyms of Factor X Deficiency
General DiscussionFactor X deficiency is a rare genetic blood disorder that causes the normal clotting process (coagulation) to take longer than normal. This causes people to bleed for a longer of amount of time. Factor X is a clotting protein (also called a clotting factor). Clotting factors are specialized proteins that are essential for proper clotting, the process by which blood clumps together to plug the site of a wound to stop bleeding. Clotting requires a series of reactions to ultimately form a clot to plug a wound. This is referred to as the clotting (coagulation) cascade. The clotting cascade involves different substances in addition to clotting factors. Factor X, which is produced (synthesized) in the liver, eventually interacts with other clotting factors and certain cells or substances, e.g. platelets or fibrinogen, to help to form a clot. Factor X deficiency is caused by a variation (mutation) in the F10 gene. In 2015, the U.S. Food and Drug Administration (FDA) approved a drug called Coagadex for adults and children over 12. This medication restores functional factor X levels. Signs & SymptomsThe signs and symptoms of factor X deficiency are highly variable; this means that how the disorder affects one person can be very different from how it affects another person. Symptoms can develop at any age. Generally, the more severe the disorder, the earlier the symptoms begin. Sometimes, factor X deficiency is broken down based on the residual amount of factor X activity. Individuals with about 40% or more protein activity have mild disorder and often do not have symptoms (asymptomatic). Individuals with 10%-40% activity have moderate disease and general symptoms associated with bleeding disorders. Individuals with 10% or less factor X activity have severe disease, particularly those with less than 1% of factor X. In some instances, the amount of secreted factor X is normal or near-normal, but cannot function normally; in other cases, FX is not secreted at all. In many disorders, the amount of residual protein activity correlates with the severity of the disease (e.g. little to no residual protein activity results in severe disease). This is not true for all bleeding disorders, but is true for factor X deficiency – generally the less protein activity the more severe the bleeding complications. Common symptoms of moderate and severe forms can include bruising easily, nosebleeds, and bleeding from the mouth and the gums. There may be blood in the urine (hematuria). Affected individuals are at risk of excessive bleeding during or after trauma or surgery. Some individuals may not have any symptoms except for when they experience trauma or surgery. Without treatment, these symptoms can occur throughout life. With the most severe forms, symptoms can begin at or shortly after birth. Symptoms can include bleeding into the joints. This is called hemarthrosis can result in progressive joint damage and degeneration, eventually limiting the range of motion of an affected joint. Bleeding into the muscles (intramuscular bleeds) can also occur, which can cause pain and stiffness in the affected muscles. Some affected individuals will develop masses of congealed blood called hematomas that can cause symptoms due to compression of nearby structures or organs. Bleeding in the stomach, intestines (gastrointestinal tract) is frequent in severe factor X deficiency. The urogenital tract can also be affected resulting in blood in the urine (hematuria) or black, tarry bloody stools (melena). There is a high risk of intracranial hemorrhaging, a life-threatening complication in which there is bleeding inside the skull. This risk can be present from birth. Sometimes, umbilical stump bleeding can result at birth. A small about bleeding is normal, but active, continuous bleeding requires medical care. The umbilical stump is the small piece of the umbilical cord that remains in the bellybutton after birth. The stump usually dries up and falls off about 7 to 21 days. Women with factor X deficiency may experience heavy menstrual bleeding (menorrhagia). Pregnant women are at a greater risk of complications with their pregnancies including miscarriage or heavy bleeding during birth. Some women can experience heavy bleeding in the time after delivery (postpartum hemorrhaging). CausesThe F10 gene creates (encodes) factor X. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, absent, or overproduced. Depending upon the functions of the particular protein, this can affect many organ systems of the body. Variations in the F10 gene result in deficient levels of functional factor X, which in affected individuals, prevents the blood from clotting properly. Consequently, affected individuals have difficulty stopping the flow of blood from a wound; but they do not bleed faster or more profusely than healthy individuals. Factor X deficiency is inherited in an autosomal recessive pattern. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Disorders inherited in a recessive pattern occur when an individual inherits the same variant gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females. Affected PopulationsFactor X deficiency affects both men and women and can occur in individuals of any ethnic or racial group. The disorder is estimated to affect about 1 in every 500,000-1,000,000 people in the general population. Rare disorders like factor X deficiency often go unrecognized or misdiagnosed, making it difficult to determine the true frequency in the general population. DiagnosisA diagnosis of factor X deficiency is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized tests. Clinical Testing and Workup Further tests known as assays are required to confirm a diagnosis and differentiate factor X deficiency from deficiencies in other clotting factors. An assay is a test that can measure the activity of certain substances in the blood. In affected individuals a factor X assay will demonstrate reduced activity of factor X. Molecular genetic testing can confirm a diagnosis of factor X deficiency, but is usually not necessary. Molecular genetic testing can detect a variation in the F10 gene, but is available only as a diagnostic service at specialized laboratories. Standard TherapiesTreatment In 2015, the FDA approved Coagadex (human coagulation factor X) for the treatment of adults and children over the age of 12 with factor X deficiency. Coagadex is a dedicated factor X concentrate that is approved for on-demand treatment and control of bleeding episodes, and for individuals, including those with mild disease, who are about to undergo surgical procedure (perioperative management). This therapy restores functional levels of factor X to affected individuals. This medication has also been authorized by the European Medicines Agency (EMA). Individuals with factor X deficiency have also been treated with prothrombin complex concentrates (PCCs), which are blood products that contain a concentrated form of four different clotting factors: II, VII, IX and X. However, the amount of each specific factor contained in these products can vary from one preparation to another, making it difficult to determine the most appropriate dosage. PCCs undergo a purification process to eliminate viruses and other pathogens. PCCs are associated with an increased risk of developing blood clots, especially following repeated administration because most people are only deficient in one of these clotting factors. Some affected individuals may be treated with fresh frozen plasma, which is a blood derivative that comes from blood donors. Fresh frozen plasma contains all of the blood clotting factors. Fresh frozen plasma can be virally inactivated, but sometimes is not virally inactivated so there can be risk of infection. The risk of infection is extremely low because donors are carefully selected and the products are screened to ensure they do not contain viruses. There is also a risk of allergic reaction. In people with mild forms of the disorder, drugs known as antifibrinolytics, can be used. These drugs prevent the breakdown of clots in the blood. Women who experience heavy menstrual bleeding can be treated with hormonal contraceptives such as birth control pills, or with antifibrinolytics. Some individuals may be treated with fibrin glue (sealants). Fibrin glue is applied directly to the site of bleeding. Fibrin is a protein that is essential to the formation of a blood clot. Fibrin glue is manufactured from various clotting factors obtained from donated plasma. Fibrin glue acts to hold platelets together to strengthen a clot. Fibrin glue is often used for surgery or dental procedures in affected individuals. Investigational TherapiesIn 2013, the FDA approved a 4-factor prothrombin complex called 4F-PCC (Kcentra®) that contains therapeutic levels of factors II, VII, IX, and X. It is approved for acquired factor deficiency resulting from the use of warfarin in individuals with major bleeding. It has been used off label for congenital factor X deficiency, but is not approved by the FDA for this indication. Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site. For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office: Toll-free: (800) 411-1222 Some current clinical trials also are posted on the following page on the NORD website: For information about clinical trials sponsored by private sources, contact: For information about clinical trials conducted in Europe,
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ReferencesJOURNAL ARTICLES Kulkarni R, James AH, Norton M, Shapiro A. Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in women and girls with hereditary factor X deficiency. J Thromb Haemost. 2018;16:849-857. https://www.ncbi.nlm.nih.gov/pubmed/29460388 Escobar MA, Auerswald G, Austin S, et al. Experience of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency undergoing surgery. Haemophilia. 2016;22:713-720. https://www.ncbi.nlm.nih.gov/pubmed/27217097 Siddon AJ, Tormey CA. Successful use of four factor-prothrombin complex concentrate for congenital factor X deficiency in the setting of neurosurgery. Lab Med. 2016;47:e35-37. https://www.ncbi.nlm.nih.gov/pubmed/27378481 Peyvandi F, Menegatti M. Treatment of rare factor deficiencies in 2016. Hematology Am Soc Hematol Educ Program. 2016;2016:663-669. https://www.ncbi.nlm.nih.gov/pubmed/27913544 Austin SK, Kavakli K, Norton M, et al. Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency. Haemophilia. 2016;22:419-425. https://www.ncbi.nlm.nih.gov/pubmed/27197801 Unold D, Tormey CA. Clinical applications of 4-factor prothrombin complex concentrate: a practical pathologists’ perspective. Arch Pathol Lab Med. 2015;139:1568-1575. https://www.ncbi.nlm.nih.gov/pubmed/26619030 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;41:359-365. https://www.ncbi.nlm.nih.gov/pubmed/25875733 Karimi M, Vafafar A, Haghpanah S, et al. Efficacy of prophylaxis and genotype-phenotype correlation in patients with severe Factor X deficiency in Iran. Haemophilia. 2012;18:211-215. https://www.ncbi.nlm.nih.gov/pubmed/21854511 Peyvandi F, Palla R, Menegatti M, et al. Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders. J Thromb Haemost. 2012;10:615-621. https://www.ncbi.nlm.nih.gov/pubmed/22321862 Menegatti M, Peyvandi F. Factor X deficiency. Semin Thromb Hemost. 2009;35:407-415. https://www.ncbi.nlm.nih.gov/pubmed/19598069 INTERNET National Hemophilia Foundation. Factor X. Available at: https://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders/Other-Factor-Deficiencies/Factor-X Accessed August 20, 2018. Summary of mutations causing rare bleeding disorders. Available at: https://cdn.ymaws.com/www.isth.org/resource/resmgr/publications/fx_mutations-2011.pdf. Accessed On: September 12, 2018. Zivelin A and Seligsohn U: supplement to Chapter 125 of Williams Hematology 8thEdition, 2010. Accessed Sept. 13, 2018. Goudeman J. Congenital factor X deficiency. Orphanet Encyclopedia, October 2009. Available at: https://www.orpha.net/consor4.01/www/cgi-bin/OC_Exp.php?lng=EN&Expert=328 Accessed August 20, 2018. Mannucci PM. Rare inherited coagulation disorders. UpToDate, Inc. 2018 Jun 1. Available at: https://www.uptodate.com/contents/rare-inherited-coagulation-disorders Accessed August 6, 2018. McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:227600; Last Update:04/08/2011. Available at: https://www.omim.org/entry/227600 Accessed August 21, 2018. The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional. The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright. National Organization for Rare Disorders (NORD) What is a hereditary bleeding disorder called?Hemophilia is usually an inherited bleeding disorder in which the blood does not clot properly. This can lead to spontaneous bleeding as well as bleeding following injuries or surgery. Blood contains many proteins called clotting factors that can help to stop bleeding.
Which of the following is a hereditary disorder of clotting factors?Hemophilia A is a hereditary bleeding disorder caused by a lack of blood clotting factor VIII. Without enough factor VIII, the blood cannot clot properly to control bleeding.
Is a group of hereditary bleeding disorders in which a blood clotting factor is missing quizlet?Hemophilia is a group of hereditary bleeding disorders in which a blood-clotting factor is missing.
Is a group of hereditary bleeding disorders?The three most common hereditary bleeding disorders are hemophilia A (factor VIII deficiency), hemophilia B (factor IX deficiency) and von Willebrand disease.
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What is a group of hereditary bleeding disorders in which a blood clotting factor is missing?
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