Materiały źródłowe

• #1 Factor V Leiden Mutation – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK534802/

  Factor V Leiden (FVL) is a point mutation of factor V resulting in an elimination of the cleavage site in factor V and factor Va. This genetic defect increases the risk of thrombosis, especially in homozygous or pseudo-homozygous FVL-mutated individuals. […] FVL is an autosomal dominant genetic condition that exhibits incomplete penetrance, meaning that not every person with the mutation will develop the disease. This activity reviews the pathophysiology and implications of factor V Leiden and highlights the role of the interprofessional team in its management. […] Factor V Leiden results from a single-point mutation in the factor V gene (guanine to adenine at nucleotide 1691) that would lead to the replacement of arginine with glutamine at amino acid 506. This abolishes the Arg506 cleavage site for activated protein C in factor V and factor Va. The consequences are enhancing the procoagulant role of factor Va and the reduced anticoagulant role of factor V.

• #2 Mechanism and pathophysiology of activated protein C-related factor V leiden in venous thrombosis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3353632/

  Factor V Leiden (FVL) is the most common heritable cause of venous thrombosis. It is caused by a single nucleotide substitution resulting in an R506Q mutation, resulting in factor V resistance to activated protein C (APC) inactivation. The genetical and molecular basis for APC resistance involves a mutation in the coagulation factors (FV) gene at nucleotide 1691 that causes the mutation Arg 506 Gln. Two reports of functional activity studies suggested that the variant Gln 506-FVa is resistant to cleavage by APC. To conclude, APC resistance caused by FVL mutation is a strong risk factor for venous thrombosis. FVL remains an important heritable cause of hypercoagulability. APC resistance and FVL mutation can be diagnosed with high sensitivity and specificity with use of clotting time-based functional assays and genetic assays, respectively, allowing for evidence-guided clinical decision making regarding the benefit of long-term anticoagulation.

• #2 Factor V Leiden – Wikipedia

  https://en.wikipedia.org/wiki/Factor_V_Leiden

  Factor V Leiden (rs6025 or F5 p.R506Q) is a variant (mutated form) of human factor V (one of several substances that helps blood clot), which causes an increase in blood clotting (hypercoagulability). Due to this mutation, protein C, an anticoagulant protein that normally inhibits the pro-clotting activity of factor V, is not able to bind normally to factor V, leading to a hypercoagulable state, i.e., an increased tendency for the patient to form abnormal and potentially harmful blood clots. […] Factor V Leiden is an autosomal dominant genetic condition that exhibits incomplete penetrance, i.e. not every person who has the mutation develops the disease. The condition results in a factor V variant that cannot be as easily degraded by activated protein C. The mutation prevents efficient inactivation of factor V. When factor V remains active, it facilitates overproduction of thrombin leading to generation of excess fibrin and excess clotting.

• #3 Pathology Outlines – Activated protein C resistance / Factor V Leiden

  https://www.pathologyoutlines.com/topic/coagulationactivatedproteinC.html

  Most common hereditary predisposition to venous thrombosis (20% of first episodes of thrombosis, 50% of familial thrombosis) […] Normally, activated protein C degrades activated factors V and VIII by cleaving specific arginine residues […] Almost all patients with activated protein C resistance have Factor V Leiden mutation that causes resistance to degradation by activated protein C […] Factor V Leiden mutations: […] 95% with activated protein C resistance have point mutation at an arginine cleavage site (Arg506Gln, 1691 G to A) called R506Q or Factor V Leiden […] Mutation causes delayed inactivation by activated protein C, prolonging its life span and procoagulant activity […] Homozygotes have 80x increased risk for venous thrombosis; risk occurs later in life […] Presence of second risk factor (genetic or acquired) is often necessary to produce thrombosis […] Acquired risk factors are smoking, malignancy, trauma, surgery, oral contraceptive use, estrogen replacement therapy, antiphospholipid antibody, heterozygosity for prothrombin G20210A, elevated serum homocysteine.

• #3 Factor V Leiden thrombophilia | Genetics in Medicine

  https://www.nature.com/articles/gim920112

  Factor V Leiden is a genetic disorder characterized by a poor anticoagulant response to activated Protein C and an increased risk for venous thromboembolism. […] Factor V Leiden is also associated with a 2- to 3-fold increased relative risk for pregnancy loss and possibly other obstetric complications, although the probability of a successful pregnancy outcome is high. […] Diagnosis requires the activated Protein C resistance assay (a coagulation screening test) or DNA analysis of the F5 gene, which encodes the Factor V protein. […] Factor V Leiden is a genetic disorder characterized by a poor anticoagulant response to APC. APC is a natural anticoagulant protein that cleaves and inactivates procoagulant Factors Va and VIIIa, thereby downregulating further thrombin generation. […] The term Factor V Leiden refers to the specific guanine to adenine substitution at nucleotide 1691 in the Factor V gene, which predicts the substitution of glutamine for arginine at the Arg 506 APC cleavage site.

• #4 Annals of Reviews & Research (ARR) | Juniper Publishers

  https://juniperpublishers.com/arr/ARR.MS.ID.555829.php

  Factor V Leiden deficiency is one of the most common inherited thrombophilias, significantly increasing the risk of venous thromboembolism (VTE). This comprehensive review explores the pathophysiology underlying Factor V Leiden mutation, emphasizing its role in dysregulating coagulation and enhancing thrombotic risk. […] The Factor V Leiden mutation alters the structure of this protein, making it resistant to other proteins that normally prevent excessive clotting. Consequently, this can cause your blood to clot more easily than normal, potentially leading to severe complications in the legs or lungs, respectively known as deep vein thrombosis (DVT) and pulmonary embolism (PE). […] Factor V Leiden refers to a point mutation at nucleotide 1691 in the Factor V gene, which substitutes adenine for guanine. It replaces arginine with glutamine at the Arg506 APC (Activated protein C) cleavage site. The mutated gene is usually referred to as FVR506Q. As a result of this substitution, Factor Va is cleaved at a slower rate by APC, leading to a diminished anticoagulant response.

• #5 Annals of Reviews & Research (ARR) | Juniper Publishers

  https://juniperpublishers.com/arr/ARR.MS.ID.555829.php

  Factor V is postulated to have dual functions, procoagulant and anticoagulant. They are induced by differential proteolysis of Factor V at sites of vascular injury. Thrombin and Factor Xa cleave Factor V to form procoagulant Factor Va, further degraded by APC (activated protein C). In contrast, APC reveals anticoagulant properties of Factor V (FVac). […] However, Factor V Leiden (FVR506Q), is only cleaved by APC at Arg306, which is insufficient to completely inactivate FVa, resulting in a 10 times slower cleavage of FVa, leading to resistance to APC. All these factors contribute to a mildly increased lifelong risk of venous thrombosis in these individuals. […] According to Vandenbroucke et al., the risk of venous thrombosis is higher in women who use oral contraceptive pills (OCPs) and carry the Factor V Leiden mutation compared to those without the mutation.

• #6 Factor V Deficiency: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/209492-overview

  Factor V is an essential component in the blood coagulation cascade. Factor V is synthesized in the liver and possibly in megakaryocytes. Factor V circulates in an inactive form. During coagulation, factor V is converted to the active cofactor, factor Va, via limited proteolysis by the serine protease a-thrombin. Factor Va and activated factor Xa form the prothrombinase complex. The prothrombinase complex is responsible for the rapid conversion of the zymogen prothrombin to the active serine protease a-thrombin. […] Inherited factor V deficiency is a rare autosomal recessive disorder that is associated with an abnormal factor V plasma level. Numerous mutations in the F5 gene have been identified in these patients. […] Factor V Leiden is a completely different inherited disorder that involves a single point mutation in the factor V gene. Factor V activity levels in patients with factor V Leiden are normal. […] Proteolytic inactivation of factor Va and factor VIIIa by activated protein C (APC) normally limits clot formation; however, factor V Leiden resists inactivation by APC. Consequently, individuals who are homozygous for factor V Leiden have a high incidence of thrombosis.

• #7 Factor V Leiden

  https://practical-haemostasis.com/Genetics/fv_leiden.html

  Resistance to Activated Protein C [APCr] was first assessed used a modified APTT-based assay. Subsequent studies have shown that in the majority of cases of APCr, it arises from a GA missense mutation at nucleotide 1691 in the F5 gene leading to an Arg506Gln mutation in which the Arginine residue at position 506 in Factor Va is replaced by a Glutamine and this abolishes an inactivation cleavage site for Activated Protein C [APC]. APC-mediated cleavage and inactivation of FVa occurs at specific residues including Arg506, 306 and 679 and Lys994. The first cleavage at Arg506, causes partial inactivation of FVa and is essential for optimal exposure of the subsequent cleavage positions. Subsequent cleavage at the other cleavage sites, most importantly Arg306, results in the complete loss of FVa cofactor activity in the Prothrombinase complex.

• #8 Factor V Leiden thrombophilia | Genetics in Medicine

  https://www.nature.com/articles/gim920112

  Because of this single amino acid substitution, Factor Va is resistant to APC and is inactivated at a 10-fold slower rate than normal, resulting in increased thrombin generation. […] The resulting mild prothrombotic state is reflected by elevated levels of d-dimer, prothrombin fragment F1 + 2, and other activated coagulation markers. […] The mutant Factor V is referred to as Factor V Leiden because Dutch investigators from the city of Leiden were the first to report the mutation.

• #9 Factor V Leiden – Blood Clots

  https://www.stoptheclot.org/learn_more/factor-v-leiden-2/

  Factor V Leiden is a blood clotting disorder. It is not a disease. […] Factor V is a protein that is needed for blood to clot properly. Some people do not have the normal Factor V protein. Instead, they have an different form called factor V Leiden. This is caused by a change (mutation) in the gene for this protein. The different gene that makes the factor V Leiden protein is inherited from one or both parents. […] The factor V Leiden protein is harder to turn off than the normal factor V protein. This makes blood clots more likely to form, a condition called thrombophilia. […] Activated protein C does not work as well on the abnormal factor V Leiden protein. Factor V Leiden resists the effects of activated protein C, so it takes longer to turn off factor V Leiden. As a result, clotting goes on longer than usual. This is why factor V Leiden is sometimes called activated protein C resistance and why people with this mutation clot more than those without it.

• #10 Factor V Leiden: Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/17896-factor-v-leiden

  Factor V Leiden is an inherited blood clotting disorder that raises your risk of deep vein thrombosis or a pulmonary embolism. A mutation in your F5 gene causes this disorder, which follows an autosomal dominant inheritance pattern. […] People with factor V Leiden have a mutation in their coagulation factor V (F5) gene. Your F5 gene controls the production of a protein called factor V, which helps your blood clot when needed (such as after an injury). The factor V Leiden mutation changes this proteins structure. This change causes it to resist other proteins that stop excessive clotting. As a result, your blood may clot more easily than it should, leading to serious complications. […] Researchers have found that the factor V Leiden mutation involves one small change in the proteins structure. This change causes factor V to resist the actions of other proteins (protein C and protein S), which normally inactivate factor V when needed to keep your blood from clotting abnormally. As a result, factor V works in overdrive, making your blood more likely to clot when it shouldnt.

• #11 Factor V Leiden and activated protein C resistance – UpToDate

  http://www.uptodate.com/contents/activated-protein-c-resistance-and-factor-v-leiden

  Factor V Leiden (FVL) results from a point mutation in the F5 gene, which encodes the factor V protein in the coagulation cascade. FVL renders factor V (both the activated and inactive forms) insensitive to the actions of activated protein C (aPC), a natural anticoagulant. As a result, individuals who carry the FVL variant are at increased risk of venous thromboembolism (VTE). […] Mechanism of factor V Leiden.

• #12

  https://step2.medbullets.com/heme/120244/factor-v-leiden

  Hypercoagulable state/thrombophilia from mutated factor V […] Pathogenesis […] review of anticoagulation pathway […] protein C (with protein S as a co-factor) inactivates factors V and VIII […] mutated factor V lacks cleavage site for activated protein C […] factor V remains active in coagulation pathway […] defective anticoagulation […] thrombosis.

• #13

  https://www.haematologica.org/article/view/5620

  The paradox might be explained by a reduced embolization risk induced by factor V Leiden. Two hypotheses have been proposed in this framework. The first one suggested that factor V Leiden may enhance local thrombin generation intensifying the local inflammatory process against the thrombus, and strengthen the clot structure by activation of thrombin-induced FXIII transglutaminase activity. […] The second hypothesis that sustains a specific effect of factor V Leiden on resistance to embolization, involves the antifibrinolytic effect of this polymorphism described in a few studies. […] Therefore, further pathophysiological studies are required to establish the mechanism(s) involved in the inhibition of fibrinolysis by factor V Leiden in vivo, including evaluation of plasma fibrin degradation products.

• #13

  https://www.haematologica.org/article/view/5620

  The study of factor V Leiden (FVL) has created many expectations but also engendered much controversy. Factor V Leiden may have developed through genetic drift or natural selection in Caucasians, possibly by conferring a reduced risk of bleeding and an evolutionary advantage, but no similar prothrombotic polymorphism has been described in other populations. […] However, the utility of such testing is under debate, as it might complicate more than facilitate the clinical management of carriers, particularly the prophylaxis of venous thrombosis in asymptomatic carriers. Moreover, factor V Leiden has a very mild effect on arterial thrombosis. These controversies may be explained by the moderate functional consequences of the activated protein C (APC) resistance caused by this polymorphism and the requirements of additional genetic and environmental risk factors and triggering factors that are ultimately responsible for the development of a thrombotic event.

• #14

  https://www.haematologica.org/article/view/5620

  The suggested antifibrinolytic mechanism associated with factor V Leiden might contribute to explain this paradox. Thus, the thrombotic tendencies in subjects with factor V Leiden are caused by the inability of activated protein C to effectively inactivate the procoagulant factor V Leiden and the resistance of these thrombi to fibrinolysis. The last feature, however, might protect against embolization. […] Independently of this controversy, all available data support the hypothesis that the diagnosis of factor V Leiden should not influence the secondary thromboprophylaxis.

• #15 Factor V Leiden – American Blood Clot Association

  https://bloodclot.org/factor-v-leiden/

  Factor V Leiden is an inherited condition caused by a specific genetic mutation in the factor V gene. This gene is responsible for producing a protein called factor V, which plays a crucial role in the clotting system. The mutation in the factor V gene leads to the production of an abnormal form of factor V, known as factor V Leiden. […] The inheritance pattern of Factor V Leiden is autosomal dominant, meaning that if one parent carries the mutation, there is a 50% chance of passing it on to their child. This means that a child who inherits the mutation from one parent will have a 50% chance of developing the condition. […] It is important to note that not all individuals who inherit the Factor V Leiden mutation will experience abnormal blood clotting. Some individuals may have no symptoms or complications, while others may develop blood clots under certain circumstances. The severity and frequency of blood clotting events can vary from person to person. […] In addition to genetics, there are other factors that can influence the risk and expression of Factor V Leiden. These include hormonal changes, such as pregnancy and the use of estrogen-containing medications, as well as lifestyle factors such as obesity and smoking.

• #16 Factor V Leiden // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/factor-v-leiden

  Factor V Leiden (FAK-tur five LIDE-n) is a mutation of one of the clotting factors in the blood. This mutation can increase your chance of developing abnormal blood clots, most commonly in your legs or lungs. […] If you have factor V Leiden, you inherited either one copy or, rarely, two copies of the defective gene. Inheriting one copy slightly increases your risk of developing blood clots. Inheriting two copies one from each parent significantly increases your risk of developing blood clots. […] Factor V Leiden can cause blood clots in the legs (deep vein thrombosis) and lungs (pulmonary embolism). These blood clots can be life-threatening.

• #17 About Factor V Leiden Thrombophilia

  https://www.genome.gov/Genetic-Disorders/Factor-V-Leiden-Thrombophilia

  Factor V Leiden is the most common inherited form of thrombophilia. The risk of developing a clot in a blood vessel depends on whether a person inherits one or two copies of the factor V Leiden mutation. Inheriting one copy of the mutation from a parent increases by fourfold to eightfold the chance of developing a clot. People who inherit two copies of the mutation, one from each parent, may have up to 80 times the usual risk of developing this type of blood clot. Considering that the risk of developing an abnormal blood clot averages about 1 in 1,000 per year in the general population, the presence of one copy of the factor V Leiden mutation increases that risk to 1 in 125 to 1 in 250. Having two copies of the mutation may raise the risk as high as 1 in 12.

• #17 About Factor V Leiden Thrombophilia

  https://www.genome.gov/Genetic-Disorders/Factor-V-Leiden-Thrombophilia

  Factor V Leiden is the name of a specific mutation (genetic alteration) that results in thrombophilia, or an increased tendency to form abnormal blood clots in blood vessels. […] A mutation in the factor V gene (F5) increases the risk of developing factor V Leiden thrombophilia. The protein made by F5 called factor V plays a critical role in the formation of blood clots in response to injury. The Factor V protein is involved in a series of chemical reactions that hold blood clots together. A molecule called activated protein C (APC) prevents blood clots from growing too large by inactivating factor V. In people with the factor V Leiden mutation, APC is unable to inactivate factor V normally. As a result, the clotting process continues longer than usual, increasing the chance of developing abnormal blood clots.

• #18 DNA analysis for Factor V Leiden (FVL) & Prothrombin gene mutation (PT20210A) | Synnovis

  https://www.synnovis.co.uk/our-tests/dna-analysis-for-factor-v-leiden-fvl-prothrombin-gene-mutation-pt20210a

  Inherited resistance to activated protein C, associated with the factor V Leiden mutation G1691A has been shown to be present in 20-50% of individuals with a history of deep vein thrombosis (DVT). […] Heterozygosity for factor V Leiden mutation is associated with a 5-10 fold increased risk of thrombosis. (Factor V Leiden genotype G/A) […] The presence of Homozygous Factor V Leiden (Factor V Leiden genotype A/A) has been shown to increase the risk of venous thrombosis by 50-100 fold.

• #19 Factor V Leiden Analysis | Laboratory Testing for the Factor v Leiden R506Q Mutation in Cleveland, Ohio | University Hospitals

  https://www.uhhospitals.org/for-clinicians/specialties/pathology/genomic-and-molecular-pathology/tests-offered/factor-v-leiden-analysis

  Factor V Leiden (F5) R506Q mutation is the most common cause of inherited thrombophilia and accounts for over 90 percent of activated protein C (APC) resistance. […] Individuals heterozygous for this mutation have an increased risk for venous thrombosis (approximately five- to tenfold). […] Individuals homozygous for this mutation have an even higher risk for venous thrombosis (approximately fifty- to one hundredfold). […] Specific acquired or environmental factors may dramatically increase this baseline risk. […] Individuals with multiple thrombophilic mutations develop venous thromboembolism at a younger age and are at higher risk for recurrent thrombosis than those with a single defect.

• #20 Factor V (Five) Leiden Mutation | Fact Sheets

  https://www.melbournehaematology.com.au/fact-sheets/factor-v-five-leiden-mutation.html

  Factor V Leiden is a common change in a gene that controls a protein called Factor V. […] Factor V is a protein involved in blood clotting and the Factor V Leiden gene change (also called mutation) is linked to an increase risk of blood clots. […] The main problem with having Factor V Leiden mutation is having an increased risk of developing blood clots. Blood clots can occur in blood vessels and can sometimes travel to different parts of the body including the lungs. Having Factor V Leiden increases your risk of having a blood clot. […] If you have one copy of the Factor V Leiden mutation (also called being a heterozygote for this gene), you are at around 8 times more at risk of developing a blood clot compared to someone your age who does not have this gene change. If you have two copies of the Factor V Leiden mutation (called homozygote), you have approximately 80 times the risk of developing a blood clot.

• #21 American College of Medical Genetics Consensus Statement on Factor V Leiden Mutation Testing | Genetics in Medicine

  https://www.nature.com/articles/gim200128

  Factor Va isolated from APC-R patient plasma was resistant to inactivation by APC. […] Subsequent work identified a single point mutation (G to A) at nucleotide 1691 of the factor V gene, which results in substitution of a glutamine for arginine at residue 506 (R506Q), one of three APC cleavage sites (R306, R506, R679). […] This mutation is known as factor V Leiden. […] Depending on the APC resistance functional assay used and the cut-off values for defining an abnormal result, the factor V Leiden mutation may account for 85-95% of patients with APC resistance. […] The factor V Leiden mutation is carried in heterozygous form by about 5% of the Caucasian population; it is rarer in Hispanic-Americans, rarer still in African-Americans, and virtually absent in Africans and Asians. […] It is believed to produce a relative risk of venous thrombosis of about 7-fold in the heterozygous state and about 80-fold in the homozygous state. […] Factor V Leiden appears to account for 90-95% of cases of APC resistance.

• #22 Factor V Leiden

  https://practical-haemostasis.com/Genetics/fv_leiden.html

  Heterozygous carriers of the FV Leiden mutation, or other mutations, who have, in addition, a null mutation within the other F5 gene leading to non-expression, results in a pseudohomozygous APC-R phenotype. […] The Factor V Leiden mutation is considered the most common inherited thrombophilia risk factor in non-black individuals, with the highest prevalence among whites [3-7%] and the lowest among Asians and Africans [0-1%]. It is found in ~50% of individuals with recurrent or familial venous thromboembolic disease and in ~60% women with a history of venous thromboembolic disease.

• #23 Factor V (Five) Leiden Mutation | Fact Sheets

  https://www.melbournehaematology.com.au/fact-sheets/factor-v-five-leiden-mutation.html

  Most people with one copy of the Factor V Leiden mutation DO NOT develop blood clots. Blood clots usually only develop when there are other risk factors for blood clots. […] Both pregnancy and the use of the pill or hormone replacement therapy (HRT) after menopause can increase the risk of developing a blood clot. […] Because the people with Factor V Leiden have blood that clots more easily, it has been suggested that this may be beneficial during times during bleeding episodes (e.g. during menstruation or after childbirth). […] No treatment to change genes is currently available. Most people who have Factor V Leiden mutation do not need any treatment but need to be careful at times when the risk of getting a blood clot may be increased (e.g. after surgery, during long flights etc). […] Sometimes people with the Factor V Leiden mutation may need to go on blood thinning medication to reduce the risk of developing blood clots. […] Maintaining a healthy weight, stopping smoking, staying active and keeping any other medical conditions under control should also help you protect against getting any blood clots.

• #24 Factor V Resistance to Activated Protein C (APC) – Hematology and Oncology – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/hematology-and-oncology/thrombotic-disorders/factor-v-resistance-to-activated-protein-c-apc

  Mutations of factor V make it resistant to its normal cleavage and inactivation by activated protein C, and they also predispose to venous thrombosis. […] Any of several mutations to factor V make it resistant to inactivation by APC, increasing the tendency for thrombosis. […] Factor V Leiden is the most common of these mutations. Homozygous mutations increase the risk of thrombosis more than do heterozygous mutations. […] The activated protein C resistance assay is a screening test for the presence of factor V Leiden. Activated protein C is added to a 5-fold dilution of patient plasma, and the coagulation time is measured. In patients with homozygous or heterozygous factor V Leiden resistance, the prolongation of the clotting time is significantly reduced because their factor V is resistant to cleavage by activated protein C. […] Confirmation of factor V Leiden is then done by DNA-based testing for the mutation.

• #25 Factor V Leiden: Symptoms, Diagnosis and Treatment

  https://www.nationwidechildrens.org/conditions/factor-v-leiden

  The presence of Factor V Leiden is easily diagnosed with a laboratory test. This test looks at an individual’s DNA to see if they are making normal Factor V or the abnormal Factor V Leiden. It also identifies if a patient has one or two copies of the Factor V Leiden gene. […] Most people with Factor V Leiden do not form abnormal clots and require no treatment. If abnormal clots become an issue, „blood-thinning” medications, like Coumadin, can be used to impair the clotting system. This will halt growth of the clot and reduce the risk of future clots. […] The most serious complications occur when clots block blood flow in the lungs and brain. In the lung, large clots impede the normal exchange of oxygen and carbon dioxide. In the brain, they may cause swelling and prevent oxygen and nutrients from reaching delicate nervous system tissue. In these situations, abnormal blood clots can become life-threatening.

• #25 Factor V Leiden: Symptoms, Diagnosis and Treatment

  https://www.nationwidechildrens.org/conditions/factor-v-leiden

  The lifetime incidence of an abnormal clot in the general population is 1 in every 100,000 people. This risk increases to 1 in every 10,000 people if one copy of the abnormal gene is present. It increases to 6 in every 10,000 people if two copies are present. This means most people with Factor V Leiden will never experience an abnormal clot in the course of their lives. […] However, when abnormal clots do form, the symptoms can be severe. The exact set of symptoms depends on the location of the abnormal clot. Common locations include leg veins (especially in adults) and at the site of indwelling plastic catheters (IVs, central lines), which are common in children with underlying chronic health conditions. […] While Factor V Leiden is one possible cause of abnormal clot formation, there are many others. Examples include abnormalities in Protein C, Protein S, Antithrombin, and Prothrombin 20210.

• #26 Factor V Leiden DNA Mutation Detection Systems – Class II Special Controls Guidance Document for Industry and FDA Staff | FDA

  https://www.fda.gov/medical-devices/guidance-documents-medical-devices-and-radiation-emitting-products/factor-v-leiden-dna-mutation-detection-systems-class-ii-special-controls-guidance-document-industry

  There are no known direct risks to patient health when tests are used as an aid to diagnosis. However, failure of the test to perform as indicated or error in interpretation of results may lead to improper medical management of patients with clotting disorders. […] Genetic testing for the FVL mutation has been performed for a number of years, but has chiefly been confined to in-house developed testing. New technological developments and increased demand for genetic tests have led to the demand for marketing of devices capable of detecting the FVL mutation and associated disease-specific polymorphisms. […] The intended use should specify what the test is intended to measure, why it is measured, and should specify populations to which the test is targeted, where appropriate. In this case, the intended use should clearly specify the FVL mutation.

• #27 Thromboembolic Disease and Factor V Leiden Defect | AAFP

  https://www.aafp.org/pubs/afp/issues/1998/0415/p1997.html

  Definitive diagnosis of the mutation requires the use of techniques based on polymerase chain reaction, although resistance to activated protein C may also be identified using relatively simple plasma testing. […] The authors conclude that the issues associated with screening for factor V Leiden are complex. […] The frequency of factor V Leiden mutation as a cause of venous thromboembolic disease needs to be recognized. Patients with venous thromboses must be screened for the presence of this mutation.

• #28 Factor V Leiden DNA Mutation Detection Systems – Class II Special Controls Guidance Document for Industry and FDA Staff | FDA

  https://www.fda.gov/medical-devices/guidance-documents-medical-devices-and-radiation-emitting-products/factor-v-leiden-dna-mutation-detection-systems-class-ii-special-controls-guidance-document-industry

  The known FVL mutation is G1691A. Additional rare mutations in Factor V are known at A1692C, G1689A and A1696G. […] FVL molecular mutation testing should include both positive and negative controls. […] You should validate the analytical sensitivity of your test, i.e., what the minimum amount of input nucleic acid is, and approximate the amount of sample required to generate this minimum input. […] You should assess interference in FVL mutation detection from any input into the system. […] FDA recommends manufacturers fully examine the reproducibility and robustness of their device. […] Prospective clinical testing to determine clinical validity and utility will generally not be necessary for the FVL mutation and polymorphisms.

• #29 Factor V Leiden

  https://mobile.fpnotebook.com/HemeOnc/Coags/FctrVLdn.htm

  Factor V is a Cofactor for Factor X. […] Defect prevents Factor V (and Va) degradation by Protein C. […] Originally named for a poor Anticoagulant response to activated Protein C (APC). […] Activated form of Factor V (Factor Va) is more slowly degraded by activated Protein C. […] Although Factor V Leiden is the most common cause of APC Resistance, it is not the only cause. […] Responsible for 95% of APC Resistance.

• #30 Factor V Leiden – Blood Clots

  https://www.stoptheclot.org/learn_more/factor-v-leiden-2/

  Factor V Leiden is an inherited disorder. Your brothers and sisters may have inherited the mutated gene, just like you did. […] Having factor V Leiden means that you have a greater chance of developing a dangerous blood clot in your legs (DVT) or lungs (PE). […] Having one factor V Leiden gene (heterozygous type) slightly increases the chance of developing a blood clot. Having two factor V Leiden genes (homozygous type) makes the risk much greater. […] There is no treatment that can prevent this disorder or make it go away. However, there are things that you can do to reduce your chances of developing a dangerous blood clot. […] You do need treatment with blood thinners if you have had a blood clot or develop one in the future. These medications (called anticoagulants) help to prevent clotting. If you have never had a blood clot, you do not need treatment with blood thinners. […] Women have a greater chance of developing a blood clot during pregnancy. Before becoming pregnant, talk with your doctor about how your risk of blood clots can be managed during pregnancy, childbirth and for six weeks postpartum. You may be treated with blood thinners during this time.

• #31 Review of Factor V Leiden Thrombophilia

  https://www.uspharmacist.com/article/review-of-factor-v-leiden-thrombophilia

  Factor V Leiden results from a single point mutation in the factor V gene that causes a poor anticoagulant response to activated protein C. […] The inheritance of the defective gene may be expressed as either homozygous or heterozygous factor V Leiden. Heterozygosity carries a relative risk of incident VTE of approximately three-to-eight fold. In contrast, homozygosity carries a relative risk of incident VTE of 80-fold. […] Individuals with this genetic mutation are at increased risk for experiencing VTE as either deep venous thrombosis (DVT) or pulmonary embolism (PE).

• #32 A case-control study on factor V Leiden: an independent, gender-dependent risk factor for venous thromboembolism | Thrombosis Journal | Full Text

  https://thrombosisjournal.biomedcentral.com/articles/10.1186/s12959-021-00328-0

  Activated protein C resistance (APCR) due to factor V Leiden (FVL) mutation (R506Q) is a major risk factor in patients with venous thromboembolism (VTE). […] More than 95% of cases with APCR abnormality are due to FVL mutation. […] The substitution mutation at G1691A results in an amino acid alteration (R506Q), leading to increased thrombin generation and a hypercoagulable state. […] The risk of thrombosis increase by 5 to 10 fold in patients with heterozygous FVL mutations while homozygotes have an increase of nearly 80 fold. […] Here, we describe the association of resistance to APC with VTE. Participants bearing APCR abnormality had a clearly significant increased risk for VTE. […] The most common manifestations in patients with APCR abnormality were DVT followed by abortion and PE. […] Despite the higher frequency of women, the second thrombotic symptom was miscarriage (22%) along with pregnancy complications (5%), accounting together for 27% of all symptoms. […] In conclusion, patients with phenotypic resistance to APC have an increased risk for VTE.

• #33 Factor V Leiden Mutation and PT 20210 Mutation – Testing.com

  https://www.testing.com/tests/factor-v-leiden-mutation-and-pt-20210-mutation/

  The risks that are associated with factor V Leiden, PT 20210, and other inherited and acquired factor deficiencies are independent. A person can have more than one risk factors for harmful blood clots, and their associated risks are cumulative. Added to inherited risks and acquired risks are controllable risk factors, such as use of oral contraceptives and hormone replacement therapy (HRT), that may worsen the combined underlying risk factors. For instance, if a woman has one gene copy with the factor V Leiden variant, she may be at about a 2 to 4 fold greater risk of developing a VTE. If she also uses oral contraceptives, the combined risk can increase to 35 times the risk for factor V Leiden heterozygosity alone, and women with factor V Leiden who take HRT have a 15-fold higher risk.

• #34 Factor V Leiden: Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/17896-factor-v-leiden

  Factor V Leiden may lead to deep vein thrombosis or a pulmonary embolism, which are serious medical emergencies. However, most people with this genetic mutation never develop these complications. […] Other than the increased risk of developing DVT or PE, factor V Leiden may increase the risk of miscarriage or other pregnancy complications, such as preeclampsia and eclampsia, placental abruption (when the placenta separates too early from the wall of your uterus), and having a fetus that grows slower than is usual. Miscarriages associated with factor V Leiden are more likely to occur later in pregnancy (after the first trimester).

• #35 Factor V Leiden thrombophilia: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/factor-v-leiden-thrombophilia/

  Factor V Leiden thrombophilia is an inherited disorder of blood clotting. Factor V Leiden is the name of a specific gene mutation that results in thrombophilia, which is an increased tendency to form abnormal blood clots that can block blood vessels. […] The factor V Leiden mutation is associated with a slightly increased risk of pregnancy loss (miscarriage). […] A particular mutation in the F5 gene causes factor V Leiden thrombophilia. The F5 gene provides instructions for making a protein called coagulation factor V. 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. […] However, in people with factor V Leiden thrombophilia, coagulation factor V cannot be inactivated normally by APC. As a result, the clotting process remains active longer than usual, increasing the chance of developing abnormal blood clots.

• #36 Factor V Leiden Disease – OpenAnesthesia

  https://www.openanesthesia.org/keywords/factor-v-leiden-disease/

  A point mutation of the Factor V gene, which codes for an elimination of the cleavage site in Factor V and activated Factor Va, is the underlying cause of Factor V Leiden (FVL) disease. […] A point mutation of the factor V gene, which codes for an elimination of the cleavage site in factor V and activated factor Va, is the underlying cause of FVL disease.1 […] Patients are at an increased risk for thrombosis as a result of this genetic defect. […] Normally, activated protein C (APC) and its cofactor protein S, function as a natural anticoagulant by inactivating factors Va and VIIIa, the primary factors implicated in the coagulation cascade.1 With FVL, APC cannot bind and inactivate factor V, which increases the risk of thrombosis (Figure 1). […] FVL may lead to increased thrombin generation beyond the hypercoagulability of pregnancy and contribute to thrombosis and generation of fibrin and fibrin degradation products, causing an overall inflammatory burden which leads to pregnancy loss.4,5 […] Despite the proposed mechanism, a causative relationship is not well established for FVL.

• #37 Effects of factor v Leiden polymorphism on the pathogenesis and outcomes of preeclampsia | BMC Medical Genetics | Full Text

  https://bmcmedgenet.biomedcentral.com/articles/10.1186/s12881-019-0924-6

  Factor V Leiden polymorphism is a well-recognized genetic factor in the etiology of preeclampsia. […] The factor V Leiden variant resists cleavage by activated protein C due to the substitution of glutamine residue with arginine at position 506 (Gln506), which is the cleavage site for activated protein C. […] The strikingly three fold increment of AST / ALT ratio, increased white blood cell (wbc) and increased uric acid levels observed in PE cases when stratified by both exons indicates that genetic disposition to FVL could be associated with susceptibility to PE and might confer poor PE outcomes. […] The inflammatory response attributed to FVL might be due to platelets activating the inflammation, with uric acid channeling macrophage and dendritic cell activation, thereby increasing proinflammatory cytokines to sustain inflammation and adverse outcomes. […] FVL mutation could lead to an inflammatory state in PE.

• #38 Factor V Leiden Thrombophilia: Genetics, Symptoms, and Treatment

  https://www.healthline.com/health/factor-v-leiden-thrombophilia

  When managing a clot due to Factor V Leiden thrombophilia, the primary goal is to dissolve the clot and prevent further clotting. […] Pregnant people with Factor V Leiden thrombophilia, particularly those with a history of blood clots or those who are homozygous for the gene (have two copies, one from each parent), may need to use anticoagulants both during and after pregnancy to reduce the risk of clotting. […] Estrogen can increase the risk of clot formation, so its important to choose alternative methods. […] Factor V Leiden thrombophilia is a genetic condition that raises the risk of abnormal blood clots, mainly in the veins.

• #39 Factor V Leiden mutation

  https://www.aboutkidshealth.ca/factor-v-leiden-mutation

  Factor V Leiden (FVL) is a blood clotting disorder caused by a change in the factor V (5) gene. […] In people with FVL thrombophilia, coagulation factor V cannot be stopped normally. This means the clotting process continues longer than usual, which increases the chance of developing abnormal blood clots. […] The FVL mutation slightly increases the risk of developing blood clots in the veins. In people with heterozygous FVL, the risk of thrombosis is increased 5-7 times. In homozygous FVL, the risk increases 25-50 times. […] There is no direct treatment for FVL disorder. Instead, the goal of management is to minimize the risk of getting a blood clot in the first place.

• #40 Treatment for Factor V Leiden, Stuck Between a Rock and a Hard Place: A Case Report and Review of Literature | Jehangir | Journal of Hematology

  https://thejh.org/index.php/jh/article/view/149/103

  There remains a need for adequate management to create a therapeutic balance in which the patient avoids a hypercoagulable state and does not end up in bleeding state due to the anticoagulation therapy. […] Current management of factor V Leiden is based on the clinical manifestations in the patient. […] Long-term management of patients with inherited thrombophilia had not been well studied. […] The possibility of creating a therapeutic balance remains an important area of research and great concern in order to provide hemodynamic stability in patients with factor V Leiden mutation. […] Factor V Leiden remains the most common cause of hypercoagulable states and people with factor V Leiden thrombophilia have a significantly higher-than-average risk of developing venous thromboembolic disease than the general population. […] Management of factor V Leiden continues to be a challenge due to the fact that the current treatment regimen has not been able to effectively provide treatment without adverse effects.

• #41 Factor V Leiden | The Foundation to Advance Vascular Cures

  https://www.vascularcures.org/factor-v-leiden

  Factor V Leiden is the name of the genetic variation that increases the tendency for the body to form large blood clots (also known as thrombophilia). […] Factor V Leiden thrombophilia is a blood clotting disease that runs in the family, meaning people are at high risk for developing this disease if someone else in their family has it. […] While factor V Leiden increases the risk for blood clots, only a small percentage of the people who have it develop abnormal clotting. […] Factor V Leiden can be confirmed by a blood test and by genetic testing. […] A health care provider may test you for factor V Leiden if you have had abnormal clotting or have a strong family history of clotting problems. […] Clinicians or providers may prescribe blood-thinners to help prevent blood clots for people who are considered high risk. […] However, this type of medication may not be needed if people with factor V Leiden have never experienced abnormal blood clots.

• #42 Factor V Leiden DNA Mutation Detection Systems – Class II Special Controls Guidance Document for Industry and FDA Staff | FDA

  https://www.fda.gov/medical-devices/guidance-documents-medical-devices-and-radiation-emitting-products/factor-v-leiden-dna-mutation-detection-systems-class-ii-special-controls-guidance-document-industry

  This document was developed as a special control to support the classification of Factor V Leiden (FVL) DNA mutation detection systems into class II (special controls). […] Genetic tests for the FVL mutation are devices that may consist of different reagents and instruments depending on the final configuration of the device, which may include polymerase chain reaction (PCR) primers, hybridization matrices, thermal cyclers, imagers, and software packages. The devices are intended as an aid in diagnosis in individuals with suspected thrombophilia. […] FDA believes that special controls, when combined with the general controls, will be sufficient to provide a reasonable assurance of the safety and effectiveness of Factor V Leiden DNA mutation detection systems. […] The detection of the Factor V Leiden mutation is intended as an aid in the diagnosis of patients with suspected thrombophilia.

• #43 American College of Medical Genetics Consensus Statement on Factor V Leiden Mutation Testing | Genetics in Medicine

  https://www.nature.com/articles/gim200128

  Factor V R506Q (Leiden), causing activated protein C (APC) resistance, was discovered in 1994 and is the most common genetic risk factor for venous thrombosis. […] Knowledge of the presence of factor V Leiden in patients and relatives can influence management and prevention of venous thrombosis in some cases. Factor V Leiden has also been associated with increased risk of recurrent pregnancy loss and placental infarction. […] The report of three unrelated probands and their families with idiopathic recurrent venous thromboembolism whose plasma was resistant to the anticoagulant effect of exogenously added APC has provided exciting new insights into the etiology of venous thromboembolism. Early epidemiologic data suggested that an abnormally low anticoagulant response to APC, termed activated protein C resistance (APC-R), was familial, with an autosomal dominant or semidominant inheritance pattern.

• #44 Factor V Leiden Test – Purpose, Results, Normal Range, and more

  https://www.apollohospitals.com/diagnostics-investigations/factor-v-leiden-test/

  The interpretation of these results will depend on your personal medical history, family history, and other factors. Your healthcare provider will discuss the best course of action based on the results. […] Its important to remember that having the mutation does not guarantee that you will experience blood clots. Many factors, including lifestyle and other health conditions, contribute to clot development. […] The Factor V Leiden test identifies a genetic mutation that makes blood clotting more likely, helping detect individuals at higher risk for conditions like DVT and PE. […] Testing positive indicates a higher risk of blood clots but does not guarantee clotting issues. Your doctor will guide you on preventive measures. […] The Factor V Leiden test is an essential diagnostic tool for identifying individuals at increased risk of developing blood clots due to a genetic mutation. While a positive result can indicate a higher risk of thrombosis, it does not mean that clotting will occur. Early detection allows for preventive measures to reduce the risk of complications and improve overall health outcomes.

• #45 Factor V Leiden Mutation | MLabs

  https://mlabs.umich.edu/tests/factor-v-leiden-mutation

  Activated protein C (APC), a serine protease, limits clot formation by proteolytic inactivation of factor Va (and VIIIa). Resistance of FVa to degradation by APC is associated with an increased risk of venous thromboemobolism (VTE). This resistance is caused by a specific point mutation in the gene coding for the coagulation factor V (F5 c.1601GA; rs6025; g.169549811CT; NC_000001.11; NM_000130.4; previously designated c.1691GA) which results in the replacement of amino acid Arg 534 (CGA) by Gln (CAA) (F5 R534Q; previously designated R506Q R506Q Leiden). This amino acid substitution prevents inactivation of factor Va by APC. […] Other genetic as well as environmental factors may also influence the risk of thrombosis.

• #46 Factor V Leiden Mutation – Anatolia Geneworks

  https://www.anatoliageneworks.com/diseases/factor-v-leiden-mutation/

  Although having this mutation increases the risk of a venous thrombotic event (VTE), there is no clinical evidence that it increases overall mortality in those who are heterozygous for the factor V Leiden mutation. […] Factor V Leiden cannot be prevented as there are no genetic treatments available to prevent the inheritance of a mutated F5 gene.

• #47 Factor V Leiden (R506Q), Prothrombin G20210A, and MTHFR C677T Variants and Thrombophilia in Qatar Biobank Participants: A Case Control Study

  https://www.mdpi.com/1873-149X/31/4/44

  F5 G1691A is a single nucleotide change that changes the G (guanine) to an A (adenine) at the 1691 position in exon 10, consequently causing an amino acid substitution (arginine to glutamine, R506Q). Factor V is a procoagulant protein that accelerates the conversion of prothrombin to thrombin, and it is inactivated by activated protein C. The FVL variant is a gain-of-function variant that causes resistance to activated protein C, thereby predisposing individuals to thrombosis. […] Molecular testing for the F5 G1691A variant and other thrombotic variants is important not only to obtain a diagnosis but to also offer valuable insights into predicting and potentially preventing future thromboembolic events.

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