Factor xi fxi deficiency, also called hemophilia c, plasma thromboplastin antecedent deficiency and rosenthal. It plays a role, as described before, in the chain reaction that is set in motion when there is an injury to a blood vessel. Unlike haemophilia a or b, there is no bleeding into joints and muscles. Additionally,theprobandandtwoofhischildren had decreased hageman factor factor xii levels. Factor xi deficiency nord national organization for rare.
Although ceu and glaucoma have been reported to occur in asso ciation with other neural crest disor ders, to our knowledge this is the first association with praderwilli syn drome and with factor xi deficiency. Factor xi fxi deficiency, also called hemophilia c, plasma thromboplastin antecedent deficiency and rosenthal syndrome, was first recognized in 1953 in patients who experienced severe bleeding after dental extractions. Factor xi deficiency in kerry blue terriers article pdf available in journal of the american veterinary medical association 20511. Factor xii is a protein involved in that complex process. Women with factor xi deficiency may also experience heavy menstrual periods or heavy postpartum bleeding. The ratio of factor xi coagulant activity to factor xi antigen was 0.
Factor xi deficiency is a bleeding disorder that interferes with the bodys clotting process. Other factor deficiencies national hemophilia foundation. Viii, ix, or xi, hemophilia a, b, or c with bleeding, vwd. This publication is available as a pdf file in english, french, spanish. Like factor xi deficiency, inhibitors affecting the intrinsic pathway may present with bleeding and prolongation of the aptt. Individuals with severe factor xi deficiency are prone to excessive bleeding after injury or surgery, but the existence of a haemorrhagic tendency in partial factor xi deficiency is controversial. The deficiency was manifested by an isolated prolonged activated partial thromboplastin time aptt after surgery. Factor xi health encyclopedia university of rochester. Women with bleeding disorders judy kauffman, rn, ms, cpnp. Factor xi deficiency aninheritedbleedingdisorder 10 symptoms forreasonsthatarestillunknown,thetendencytobleedisnot. Report of a case an 8monthold ashkenazi jewish boy was found to have ceu in the. The objective of this document is to guide diagnosis and management of patients with rare coagulation disorders. Most commonly inherited as an autosomal recessive trait an autosomal dominant pattern of inheritance is possible, as the dimeric structure of factor xi may result in a dominant negative effect through intracellular heterodimer formation blood 2004.
From a survey of factor xi levels among 428 unrelated healthy ashkenazi jews, 35 had partial factor xi deficiency factor xi levels 0. Its incidence is estimated at 1 in 100,000 in the general population. The objective of this document is to guide diagnosis and management of patients with rare coagulation disorders rcd. The f11 gene mutations that cause factor xi deficiency reduce the amount of factor xi in the bloodstream or result in the production of a factor xi protein with impaired function. His offspring seemed to be heterozygous carriers of pta deficiency. Activators of factor xi include thrombin factor iia, factor xiia, and itself ie. Boltonmaggs summary factor xi fxi deficiency has a more variable bleeding tendency than hemophilia a or b. While rare, hemophilia is the bestknown coagulation disorder that is usually passed from parents to children. Factor xi deficiency the rosenthal syndrome, an autosomal recessive genetic defect, was transmitted to a patient after orthotopic liver transplantation. Factor x deficiency genetic and rare diseases information. These very rare factor deficiencies, from factor xiii deficiency, the rarest, occurring in an estimated 1 out of 5 million people, to factor xi deficiency, occurring in about 1 out of 100,000, were all discovered and identified in the 20 th century. Intravenous infusion of polyphosphate into wt mice also induced.
Unlike factor xi deficiency, vwd and avws have abnormal testing for vwf function and normal factor xi levels. People with factor xi 11 deficiency, also called hemophilia c, have low levels of factor xi. Factor xii deficiency is a rare genetic blood disorder that causes prolonged clotting coagulation of blood in a test tube without the presence of prolonged clinical bleeding tendencies. In humans, the protein circulates in plasma at a concentration of 30 nm 1545 nm almost entirely as a noncovalent complex with the glycoprotein high molecular weight kininogen hk.
Factor xi deficiency is a rare genetic bleeding disorder caused by reduced levels and insufficient activity of a blood protein called factor xi. The rare coagulation disorders paula hb boltonmaggs introduction the rare coagulation disorders are inherited abnormalities of hemostasis that may present significant difficulties in diagnosis and management. The overall frequency of these disorders in the general population is low with the exception of factor xi deficiency. The information contained on this web site is provided for research purposes only. Maggs et al, 2004a the rcd are here defined as monogenic bleeding disorders caused by deficiency of a soluble coagulation factor or factors. Most patients with confirmed fxii deficiency are asymptomatic. The normal range for factor xi activity levels is 70 to 150 udl, or 70% to 150%. Factor xi fxi deficiency results in a mild bleeding disorder that was first recognized in 1953 1 when an american physician reported a jewish family with abnormal bleeding after tonsillectomy and dental extractions. A deficiency of functional factor xi slows blood clotting, causing episodes of abnormal bleeding. A factor xi level can be obtained if there is a high level of suspicion for fxi deficiency. Factor xi or plasma thromboplastin antecedent is the zymogen form of factor xia, one of the enzymes of the coagulation cascade. Studies have indicated that reductions in the activities of factor xii and factor xi can protect against the development of thrombosis in animal models. Other terms for this disorder include plasma thromboplastin antecedent pta deficiency, rosenthal syndrome, and hemophilia c see image below. Factor xi deficiency fxi inhibitors contact pathway.
Factor xi plasma thromboplastin antecedent deficiency is a blood coagulation abnormality occurring in high frequency in ashkenazi jews. Factor xi deficiency is associated with lower risk for cardiovascular. As with some individuals with mild factor xi deficiency, the aptt may be normal in some individuals with mild vwd and avws. Neonatal bleeding is not described unless provoked by surgery e. However, factor xii and pk levels were not reduced in fxianimals, indicating factor xi deficiency blunted contact activation.
Acquired factor x deficiency has a variety of causes including liver disease, vitamin k deficiency, exposure to certain medications that affect clotting, and certain types of cancer. It is caused when a persons body doesnt produce enough of protein in the blood factor xi that helps blood clot or the factor xi doesnt work properly. Management of patients with factor xi deficiency is particularly challenging due to poor correlation between degree of factor xi deficiency and bleeding risk and the reported thrombotic risk of factor xi concentrates. Pattern of symptoms in 93 iranian patients with severe factor xiii deficiency. Factor xi deficiency is associated with lower risk for. Plasma levels of the contact factors factor xii and prekallikrein were reduced in wt mice after clp, consistent with induction of contact activation. Oct 30, 2019 factor xi fxi deficiency is an autosomal disorder that may be associated with bleeding. Factor xi deficiency or hemophilia c request pdf researchgate. Factor xi deficiency is one of the rare inherited coagulation factor deficiencies. The bovine form of the disease was first discovered in holstein cattle in ohio in 1969.
In hemophilia a and b, the bleeding tendency is clearly related to factor level. Hereditary factor xi deficiency is relatively common in jews of ashkenazi origin, and epidemiologic studies of this population have revealed that severe factor xi deficiency confers protection against both ischemic stroke and deepvein thrombosis although not from acute myocardial infarction. The patient was a 69yearold female planned for an ivor lewis esophagectomy for carcinoma. This condition is classified as either partial or severe based on the degree of deficiency of the factor xi protein. Xi deficiency, uncommon, unlike hemophilia a and b, spontaneous. Fxi deficiency, also known as hemophilia c, plasma thromboplastin antecedent deficiency, or rosenthal syndrome, was first described in 1953.
Factor xii deficiency hageman factor is a very rare coagulation disorder. This document replaces the 2004 uk haemophilia centre doctors organization ukhcdo rare coagulation disorders guideline bolton. Chs strives to improve the health and quality of life for all people with inherited bleeding disorders, and to find a cure. Anesthetic management using peripheral nerve block in.
Initial screening tests for fxi deficiency would reveal an isolated prolonged activated partial thromboplastin time aptt. The role of fxii is that it acts as an activator of factor xi. Heredity and coagulation studies in ten families with factor xi plasma thromboplastin antecedent deficiency. Thrombin is the physiological activator of fxi rather than fxiia as previously thought. Common features of factor x deficiency may include easy bruising, frequent nosebleeds, bleeding gums, blood in the urine, and prolonged bleeding after minor injuries. Women with bleeding disorders judy kauffman, rn, ms, cpnp the original chapter on women with bleeding disorders for this manual was written by the late renee paper, rn, ccrn who was a woman with a bleeding disorder and a tireless pioneer advocate for women who bleed. Additional document downloads will be added as available. The severity of the disorder and the associated signs and symptoms can vary significantly from person to person. Factor xi deficiency nord national organization for. Factor xi fxi deficiency is a rare inherited coagulation disorder characterized by infrequent spontaneous bleeding, but increased risk of hemorrhagic complications especially after trauma or. If your results are lower than normal, it means you may have factor xi deficiency. Like factor xi deficiency, vwd is an inherited autosomal bleeding disorder that can present at any age. Factor xi is one of more than a dozen proteins involved in blood clotting. Like many other coagulation factors, it is a serine protease.
Clinical presentation rare coagulation disorders rare. However, the bulk of the evidence is in the form of case reports and case series with no control group making it. Clotting factors are specialized proteins that are essential for proper clotting, the process by which blood solidifies like glue to plug the site of a wound to stop bleeding. Factor xi fxi deficiency was described in three members a jewish family in the usa and was called hemophilia c to distinguish it from hemophilias a and b.
Although factor xi is not as critical to clotting as other factors, a person with factor xi deficiency may still need treatment and attention. Factor xi is part of the coagulation cascade and functions, when activated as part of the intrinsic pathway, to activate factor ix. In israel, fxi deficiency occurs in up to 8% of ashkenazi jews because of intermarriage. However, its incidence is high within the ashkenazi jewish.
Factor xii deficiency nord national organization for rare. Factor xi deficiency is an example of a biochemical genetic defect that will be amenable to accurate, rapid and inexpensive testing. Factor xi fxi is the zymogen of the coagulation protease factor xia fxia. If your results are less than 15% of normal, you may have severe factor xi deficiency. Management of severe factor xi deficiency with factor xi. Factor xi deficiency is a rare, autosomal recessive disorder present in 1. Factor xi deficiency aninheritedbleedingdisorder 6 figure1 showswhatcanhappen whenoneoftheparentshasa defectivegene. Jan 22, 2019 acquired noninherited factor x deficiency, which is the most common form of the disorder, generally occurs in people with no family history of the disorder. It is caused by a deficiency of the factor xii hageman factor, a plasma protein glycoprotein. Factor xi deficiency haemophilia foundation australia. About 250 mutations in the f11 gene have been found to cause a rare bleeding disorder called factor xi deficiency. Individuals with severe deficiency have only a mild bleeding tendency, which is typically provoked by surgery, but the risk of bleeding is not restricted to individuals with severe. If you find this website useful, please reference our publication, saunders et al, 2005.
Factor xi fxi deficiency is an autosomal disorder that may be associated with bleeding. Bleeding in people with factor xi deficiency is sometimes affected by other factors or may be apparent only. Guideline for the diagnosis and management of the rare. These factors or enigmas contribute to the variable management of patients with this coagulation factor deficiency, but recent research is helping to clarify some. Factor xi deficiency alters the cytokine response and.
Congenital factor xi deficiency is an inherited bleeding disorder characterized by reduced levels and activity of factor xi fxi resulting in moderate bleeding symptoms, usually occurring after trauma or surgery. Activation of factor xi leads to the initiation of the intrinsic pathway of the coagulation cascade. Improvement in laboratory tests to clearly identify carriers and normals for this condition will eventually lead to its control and to the further improvement of the holstein breed. Factor xi fxi deficiency is a rare inherited coagulation disorder associated with prolonged activated partial thromboplastin time aptt. Fxi deficiency may present at any age and even patients with major deficiency may be diagnosed late in life. Fxi is unique among coagulation proteases in that it is a dimer of identical 80 kda subunits. Fxii appears to be not essential for blood clotting, as individuals with this condition are. Factor xi plasma thromboplastin antecedent deficiency in. Pdf the management of factor xi deficiency is not straightforward for three reasons. Concurrently, the patient has a rare factor xi deficiency that can be associated with bleeding tendencies. An update on factor xi structure and function sciencedirect.
Factor xi deficiency acquired by liver transplantation. Jan 01, 2009 factor xi fxi deficiency was described in three members a jewish family in the usa and was called hemophilia c to distinguish it from hemophilias a and b. This report describes if a person has a variant associated with factor xi deficiency and the potential for a higher risk of excessive bleeding following trauma or surgery, but it does not. Factor xi plays an integral role in the intrinsic pathway of the coagulation cascade figure 1 7.
Pregnant patients with factor xi deficiency present a particularly complex scenario because frequently their diagnosis is revealed through laboratory testing and the clinical implications are unclear. Novoseven, novo nordisk, bagsvaerd, denmark and the anti. Factor xii deficiency is a deficiency in the production of factor xii fxii, a plasma glycoprotein and clotting factor that participates in the coagulation cascade and activates factor xi. Coexistence syndrome, congenital ectropion glaucoma, xi. Factor xi deficiency is a disorder that can cause abnormal bleeding due to a shortage deficiency of the factor xi protein, which is involved in. Fxii appears to be not essential for blood clotting, as individuals with this condition are usually asymptomatic and form blood clots in vivo. Factor xii does play an important role in clot formation during in vitro measurements of the partial thromboplastin time, which causes these measurements to be markedly prolonged in patients with factor xii deficiency, usually well beyond even what is seen in hemophilia a, hemophilia b, or factor xi deficiency. Factor xi deficiency genetic and rare diseases information. Factor xi deficiency and its management 3 clinical picture and inheritance fxi deficiency is distinguished clinically from hemophilia a and b by the absence of spontaneous bleeding into joints and muscles and by its occurrence in individuals of either sex. Effect of antihemophilic factor on onestage clotting tests.
Factor xi deficiency is an inherited bleeding disorder that is caused by a. However, regardless of the severity of the protein deficiency, most. Bleeding disorders affect females as well as males. Request pdf factor xi deficiency or hemophilia c factor xi fxi is the zymogen of a plasma protease fxia that sustains thrombin generation during. As a result, people affected by this condition may have difficulty stopping the flow of blood following dental extractions, trauma or surgery. Clotting factors are specialized proteins that are essential for proper clotting, the process by which blood solidifies like glue to plug the site of a wound to stop. Factor xi deficiency is a disorder that can cause abnormal bleeding due to a shortage deficiency of the factor xi protein, which is involved in blood clotting. Unlike factor xi deficiency, acquired factor inhibitors often present with severe spontaneous bleeding, the aptt will not correct in a mixing study, and the activity of the implicated factor will be low. This disorder, while usually mild, can cause nosebleeds, easy bruising, bleeding under the skin, bleeding of the gums, and prolonged or excessive bleeding following surgery, dental procedures, or trauma.
This condition is quite rare and happens most often among ashkenazi jews. An inherited deficiency of factor xi results in a bleeding disorder that has been documented in humans, dogs, and cattle. Three independent point mutations that result in a blood coagulation abnormality have been identified in the factor xi gene of six unrelated ashkenazi patients. Factor xi is a 160 kilodalton glycoprotein proenzyme that is produced by the liver and megakaryocytes. This new handbook will cover all aspects of the practical mangement of commonly encountered thrombotic and bleeding disorders, with emphasis on clinical diagnosis, treatment and daytoday management. Unlike factor xi deficiency, acquired factor inhibitors often present with severe spontaneous bleeding, the aptt will not correct in a mixing study, and the activity of the implicated factor. Mar 02, 2017 factor xi is part of the coagulation cascade and functions, when activated as part of the intrinsic pathway, to activate factor ix. Feb 05, 2016 factor xi deficiency is a bleeding disorder that interferes with the bodys clotting process.
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