Factor xiii deficiency genetics home reference nih. Approximately one in every three to five million people suffer from congenital factor xiii fxiii deficiency globally. Factor xiii is a protein that stabilizes blood clots factor xiii f xiii or factor is one of the 12 clotting factors that are labeled factors i to xiii factors v and vi actually denote the same clotting factor. Hemostasis may be achieved with levels as low as 2% to 3%. Factor xiii deficiency an overview sciencedirect topics. When the protein, prothrombin, is activated to make thrombin, this helps change fibrinogen factor i into fibrin, which is needed to form a stable clot. Specifically, individuals with factor xiii deficiency form blood clots like normal, but these clots are unstable and often break down. New developments in the management of congenital factor xiii. Correlates mixing study results with coagulation test results 2. Genetic researcher center in noncommunicable disease, zahedan university of medical sciences. Factor xiii deficiency is normally treated with fresh frozen plasma, cryoprecipitate or crude factor xiii concentrate from placenta.
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. Factor xiii deficiency nord national organization for. It is not well known, even among health professionals. Umbilical bleeding is the most common and evocative symptom. Fxii appears to be not essential for blood clotting, as individuals with this condition are usually asymptomatic and form blood clots in vivo. The patients usually present in emergengy with acute abdomen and diagnosis is difficult. State of californiahealth and human services agency. Congenital deficiency of factor fibrinstabilizing factor. Spontaneous rupture of spleen due to factor xiii defieciency is a rare cause of abdominal pain with disastrous consequences and can be easily confused with other abdominal pathologies until a strong possibility is entertained. Factor xiii deficiency has been classified into two categories. Severe congenital factor xiii subunit a deficiency is an ex tremely rare, autosomal recessive disorders. This report deals with the genetic form of factor xiii deficiency, which is. 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. Factor xii is also known as hageman factor, named after the patient in whom this condition was.
To clarify the genetic bases of these diseases, previously reported cases of the type i deficiency were examined at the dna level. The body produces less factor xiii than it should, or the factor xiii is not working properly, therefore the clotting reaction is blocked prematurely and the blood clot does not form. If the condition is not treated, affected individuals may have episodes of excessive and. Factor xiii deficiency is a rare inherited coagulopathy. Prepares a stepwise ptt and pt mixing study protocol 2. Aug 16, 2011 factor xiii deficiency is an extremely rare inherited blood disorder characterized by abnormal blood clotting that may result in abnormal bleeding. Hereditary deficiency of this enzyme is a rare cause of a lifelong bleeding disorder, and homozygotes for this autosomal recessive disorder have factor xiii activity. Factor xiii deficiency affects males and females in equal numbers. Nugent division of hematology, childrens hospital of orange county, orange, ca, usa summary. Coagulation factor xiii fxiii is a protein that promotes fibrin stabilization by forming multiple covalent crosslinks between fibrin monomers. Individuals of any race or ethnicity can be affected. Factor xiii deficiency categorized among rare bleeding disorders and thought to be occur in about 1 in million in general population3,4,5.
Factor xiii fxiii deficiency is an extremely rare bleeding disorder rbd with estimated incidence of 1 per 2 million. This form of the disorder is referred to as type ii factor xiii deficiency. Visit the uncommon factor deficiencies consult topic for additional information about characteristics of acquir ed and inherited fxiii deficiency. Other factor deficiencies national hemophilia foundation. Jul 21, 2017 factor v deficiency may be inherited or acquired after birth. Factor deficiency with severe hemorrhagic diathesis. There is a 1in2 chance that a child will be a carrier. The fa1 gene provides instructions for making one part, the a subunit, of a protein called factor xiii. Aug 01, 2019 the hemostatic system, consisting of blood vessels and blood, plays a crucial role in human survival. There are several options for this including chorionic villus sampling cvs early in pregnancy or amniocentesis around 15 to 20 weeks or so.
Learn more about factor xiii fxiii deficiency, also called fibrin stabilizing factor deficiency. Coagulation mixing studies learning objectives at the conclusion of this webinar, the participant 1. People with congenital or inherited factor xiii deficiency are born with low levels of factor xiii in the blood. Factor xiii deficiency genetic and rare diseases information. The majority of these conditions were only identified within the last 6070 years.
Diagnosis and classification of factor xiii deficiencies. Xiiia is an enzyme of the blood coagulation system that crosslinks fibrin. Factor xiii deficiency, a primer for anesthesiologist medigraphic. A hitherto undescribed congenital haemorrhagic diathesis probably due to fibrin stabilizing factor deficiency. Factor deficiency causes inherited factor deficiency. Explains why the mixing study is an acute care assay 4. Factor xiii deficiency is an extremely rare bleeding disorder caused by the depletion of factor xiii in blood.
Factor xiii deficiency occurs exceedingly rarely, causing a severe bleeding tendency. Acquired factor xiii fxiii deficiency is a rare bleeding disorder that can manifest with spontaneous or delayed lifethreatening hemorrhage. C h ro mo g e n i c a s s ay factor xiii, qualitativ e, with reflex to factor xiii 1. Review article current understanding in diagnosis and. Beside congenital fxiii deficiency, due to fxiii gene mutations, severe acquired fxiii deficiency has been described in association with autoantibodies against coagulation fxiii. Inherited factor xiii deficiency fxiiid is a rare bleeding disorder affecting the final stage of the coagulation system and resulting in a bleeding diathesis. Bleeding ranges from mild to severe depending on how severe the deficiency is. Factor xiii is a tetrameric zymogen composed of two catalytic a subunits fxiiia2 bound to two. List of factor xiii deficiency medications 3 compared. In iran, a middle eastern country with a high rate of. The importance of the plasma coagulation system in protecting life and preventing further blood loss following transection of a blood vessel has been understood for a long time.
A collection of disease information resources and questions answered by our genetic and rare diseases information specialists for factor xiii deficiency. The severity of factor xiii deficiency bleeds can vary greatly from one person to another. Her hemorrhagic manifestations were repeated and severe. Inherited factor xiii fxiii deficiency is a rare bleeding disorder that. This protein plays a critical role in the coagulation system, which is a series of chemical reactions that forms blood clots in response to injury. 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. The overall frequency of these disorders in the general population is low with the exception of factor xi deficiency. Its caused by a recessive gene, which means that you have to inherit the gene from both of. The diagnosis is usually made on high degree of clinical suspicion and falling. Factor xiii deficiency national hemophilia foundation, usa. Mice lacking the gene for factor xii, however, are less susceptible to thrombosis. Factor xii deficiency genetic and rare diseases information. The incidence of factor xiii deficiency has been estimated to be between 1 in 2,000,0005,000,000 people in the general population.
Deficiency of xiii worsens clot stability and increases bleeding tendency. Factor xiii deficiency can be diagnosed before birth prenatally if there is a family history. Factor xiii deficiency canadian hemophilia society, 2001 explains how factor xiii deficiency is passed on, what causes it, diagnosis, symptoms, treatments, preventing and treating bleeds, issues relating to women, pregnancy and fertility, lifestyle and vaccinations. Plasma factor xiii binds specifically to fibrinogen molecules containing gamma chains.
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. Factor xiii deficiency nord national organization for rare. Factor vii initiates the clotting sequence when it binds to tissue factor upon exposure to circulating blood, upon blood vessel injury. This report presents the first case of factor deficiency in an adult female. Signs and symptoms occur as the result of a deficiency in the blood clotting factor , which is responsible for stabilizing the formation of a blood clot. Congenital factor xiii deficiency is very rare, affecting only 1 in 2 million people about 100125 people in the us. Type i factor xiii deficiency is caused by a genetic.
This francecoag network study assessed 33 patients with congenital factor xiii fxiii deficiency presenting fxiii levels pdf abstract background. Factor v deficiency is usually caused by mutations in the f5 gene, which provides instructions for making a protein called coagulation factor v. Homozygote and double heterozygote have plasmatic factor xiii activity less than 1%, responsible of bleeding syndrome. It is caused by a deficiency of the factor xii hageman factor, a plasma protein glycoprotein. This coagulation blood disorder is inherited in an autosomal recessive manner. Factor xii deficiency is a rare disorder that is inherited in an autosomal recessive manner.
This rare disorder, also known as proconvertin deficiency or alexanders disease, is often diagnosed at birth. Factor concentrates for the treatment of factor xiii deficiency. Causes of acquired deficiency include immunemediated inhibition, as well as nonimmune fxiii hyperconsumption or hyposynthesis. Even though the initial clot forms and bleeding stops, the clot will eventually break down. Even though the initial clot forms and bleeding stops, the. Indicates the clinical purposes for ptt mixing studies 3. Inbal a, oldenburg j, carcao m, rosholm a, tehranchi r, nugent d. Most patients with factor xiii deficiency only lack functional subunit a protein with a frequency of around 1 in 5 million individuals. Pdf coagulation factor xiii gene, protein structure and function coagulation factor xiii fxiii is a tetrameric fxiiia2b2 protransglutaminase. While a lack of factor xii does not cause affected individuals to bleed abnormally, the blood takes longer than normal to clot in a test tube. Factor xiii deficiency is a rare bleeding disorder. This protein is part of a group of related proteins called coagulation factors that are essential for normal blood clotting.
Compared with the halflife of other coagulation factors, the halflife of f xiii is very long 9. Figure 1 shows what can happen when a carrier of factor xiii deficiency has children with. The majority of these conditions were only identified within the. Factor xiii deficiency fxiiid is a rare bleeding disorder with an estimated prevalence of 1 in 2million population worldwide. Inherited factor xiii deficiency results from mutations in the fa1 gene or, less commonly, the fb gene.
Clotting factors are specialized proteins that are essential for the blood to clot properly. Nov, 2019 in the sensitivity analysis, with removal of each study in turn, the association between vitamin d deficiency and ad ranged from 1. Two novel and one recurrent missense mutation in the factor xiii a gene in two dutch patients with factor xiii deficiency. Some patients have more severe complications, while others have only mild complications. Factor xiii fxiii deficiency is an inherited bleeding disorder caused when persons body doesnt produce enough of a protein in the blood factor xiii which helps blood clot or the factor xiii doesnt work properly. 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. Factor xiii is the last clotting factor in the coagulation cascade to insure strength and stability to fibrin clots. Aug 01, 2019 inbal a, oldenburg j, carcao m, rosholm a, tehranchi r, nugent d. Factor xiii is the final enzyme in the coagulation cascade and is responsible for catalyzing the intermolecular crosslinking of fibrin polymers, therefore increasing the mechanical rigidity of the fibrin clot. Vitamin d deficiency as a risk factor for dementia and. The purpose of this booklet is to describe this bleeding disorder. Researchers have identified an inherited form and a less severe form that is acquired during a persons lifetime. Inheritance of deficiency of fibrinstabilizing factor.
The incidence of factor vii deficiency is estimated to be 1 in 300,000 to 500,000 people, and affects men and women equally. Umbilical cord bleeding is common in factor xiii deficiency, reported in almost 80% of cases. Factor xiii deficiency is a rare, genetic bleeding disorder characterized by deficiency of clotting factor xiii. After birth, factor xiii deficiency can be diagnosed using a sample of blood for testing in the laboratory. Factor xiii deficiency great ormond street hospital. Successful prophylactic treatment for bleeding in a girl with severe hereditary prothrombin deficiency using a. Identification of a new leu354pro mutation responsible for factor xiii deficiency. It is transmitted by autosomal recessive inheritance. Factor xiii deficiency the medical biochemistry page. Figure 1 shows what can happen when a carrier of the defective gene has a child with another carrier.
Deficiency of fxiii is associated with reduced clot stability, and therefore ecchymoses or hematomas are usually seen 24 to 36 hours after trauma. Factor x deficiency is often caused by an inherited defect in the factor x gene. Jun 24, 2011 factor xii deficiency is an inherited disorder that affects a protein factor xii involved in blood clotting. Hereditary deficiency of factor xiii is an extremely rare condition. Factor x deficiency, also called stuartprower factor deficiency, is a condition caused by not having enough of the protein known as factor x in your blood. Manno, in blood banking and transfusion medicine second edition, 2007. Inhibitors and other complications national hemophilia. Treatment of rare factor deficiencies in 2016 hematology. Unlike other clotting factor deficiencies, factor xii deficiency is totally asymptomatic and does not cause excess bleeding. Thompson a r, harter l a, manual of hemostasis and thrombosis. Boltonmaggs summary factor xi fxi deficiency has a more variable bleeding tendency than hemophilia a or b. Fxii deficiency tends to be identified during presurgical.
Factor ii 2 deficiency also called prothrombin deficiency means someone does not have enough factor ii, which is a clotting factor protein called prothrombin. Fxiii is also known as fibrinstabilizing factor and is responsible for crosslinking of the fibrin polymer. Factor xiii deficiency haemophilia foundation australia. Signs and symptoms occur as the result of a deficiency in the blood clotting factor , which is responsible for stabilizing the formation of. These inhibitors, which occurs very rarely but may cause life. Deficiency of fxiii is associated with reduced clot stability, and therefore ecchymoses or. Therefore, if the diagnosis of severe congenital fxiii deficiency is confirmed.
Factor x deficiency can also be due to another condition or use of certain medicines. Factor xiii deficiency is an autosomal recessive congenital bleeding disease. Division of hematology, childrens hospital of orange county, orange, ca, usa. Factor xiii deficiency is an autosomal recessive disorder. They work together as part of the coagulation cascade, which is a series of chemical reactions that forms blood clots in response to injury. Factor xiii deficiency is a congenital disorder that is inherited as an autosomal recessive trait and is associated with a variable bleeding tendency acquired factor xiii deficiency is associated with liver failure, inflammatory bowel disease, leukemia, disseminated intravascular coagulation, henochschonlein purpura, systemic lupus.
Additional document downloads will be added as available. Revised 6 2019 dispensing amount for all factor recombinant products must be within three percent aggregate of the prescribed target dose. For patients receiving factor viii or factor ix products for prophylaxis and breakthrough bleeding episodes, two separate. Naderi m md1, dorgalaleh a msc2, tabibian sh msc2, alizadeh sh phd2, eshghi p md3, solaimani gh md1. Factor xii deficiency nord national organization for rare. Signs and symptoms of inherited factor xiii deficiency begin soon after birth, usually with abnormal bleeding from the umbilical cord stump.
Its prevalence depends on geographic region and is higher in areas in which. Factor xiii deficiency is an inherited bleeding disorder. Diagnosis is difficult because many of the tests typically used to test coagulation eg, pr othrombin. The incidence is one in a million to one in five million people, with higher incidence in areas with consanguineous marriage such as iran that has the highest global incidence of the disorder. This information booklet on factor xiii deficiency was prepared by.
Factor xiii deficiency is an extremely rare inherited blood disorder characterized by abnormal blood clotting that may result in abnormal bleeding. Factor vii fvii deficiency is a rare hereditary hemorrhagic disease caused by the diminution or absence of this coagulation factor. Pdf congenital factor xiii deficiency associated with. Factor x aids in the formation of thrombin from prothrombin, in the clotting cascade.
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