Factor V Leiden: Difference between revisions
I just changed this to D68.8, but there has actually been an update of ICD-10 to Version 4. In this update a new code has been introduced, D68.5, for Primary Thrombophilia, which is what Factor V Leiden is. |
Eddideigel (talk | contribs) →Epidemiology: changed 1/250, 1/125, 1/12 into 4/1000, 8/1000, 80/1000; the former are difficult to compare intuitively |
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Studies have found that about 5 percent of Caucasians in North America have factor V Leiden. The condition is less common in Hispanics and African-Americans and is extremely rare in people of Asian descent. |
Studies have found that about 5 percent of Caucasians in North America have factor V Leiden. The condition is less common in Hispanics and African-Americans and is extremely rare in people of Asian descent. |
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Up to 30 percent of patients who present with [[deep vein thrombosis]] (DVT) or [[pulmonary embolism]] have this condition. 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 ([[heterozygous]]) increases by fourfold to eightfold the chance of developing a clot. People who inherit two copies of the mutation ([[homozygous]]), one from each parent, may have up to 80 times the usual risk of developing this type of blood clot.<ref>What do we know about heredity and factor V Leiden thrombophilia? http://www.genome.gov/15015167#Q5</ref> 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 between |
Up to 30 percent of patients who present with [[deep vein thrombosis]] (DVT) or [[pulmonary embolism]] have this condition. 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 ([[heterozygous]]) increases by fourfold to eightfold the chance of developing a clot. People who inherit two copies of the mutation ([[homozygous]]), one from each parent, may have up to 80 times the usual risk of developing this type of blood clot.<ref>What do we know about heredity and factor V Leiden thrombophilia? http://www.genome.gov/15015167#Q5</ref> 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 between 4 in 1,000 to 8 in 1,000. Having two copies of the mutation may raise the risk as high as 80 in 1,000. It is unclear whether these individuals are at increased risk for ''recurrent'' venous thrombosis. While only 1 percent of people with factor V Leiden have two copies of the defective gene, these [[homozygous]] individuals have a more severe clinical condition. The presence of acquired risk factors for venous thrombosis—including [[tobacco smoking|smoking]], use of estrogen-containing (combined) forms of [[hormonal contraception]] use, and recent [[surgery]]—further increase the chance that an individual with the factor V Leiden mutation will develop DVT. |
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Women with factor V Leiden have a substantially increased risk of clotting in [[pregnancy]] (and on [[estrogen]]-containing birth control pills or hormone replacement) in the form of deep vein thrombosis and pulmonary embolism. They also may have a small increased risk of [[preeclampsia]], may have a small increased risk of low birth weight babies, may have a small increased risk of [[miscarriage]] and [[stillbirth]] due to either clotting in the placenta, umbilical cord, or the fetus (fetal clotting may depend on whether the baby has inherited the gene) or influences the clotting system may have on placental development.<ref name="Rodger">{{cite journal |author=Rodger MA, Paidas M, McLintock C, ''et al.'' |title=Inherited thrombophilia and pregnancy complications revisited |journal=Obstetrics and Gynecology |volume=112 |issue=2 Pt 1 |pages=320–24 |year=2008 |month=August |pmid=18669729 |doi=10.1097/AOG.0b013e31817e8acc}}</ref> Note that many of these women go through one or more pregnancies with no difficulties, while others may repeatedly have pregnancy complications, and still others may develop clots within weeks of becoming pregnant. |
Women with factor V Leiden have a substantially increased risk of clotting in [[pregnancy]] (and on [[estrogen]]-containing birth control pills or hormone replacement) in the form of deep vein thrombosis and pulmonary embolism. They also may have a small increased risk of [[preeclampsia]], may have a small increased risk of low birth weight babies, may have a small increased risk of [[miscarriage]] and [[stillbirth]] due to either clotting in the placenta, umbilical cord, or the fetus (fetal clotting may depend on whether the baby has inherited the gene) or influences the clotting system may have on placental development.<ref name="Rodger">{{cite journal |author=Rodger MA, Paidas M, McLintock C, ''et al.'' |title=Inherited thrombophilia and pregnancy complications revisited |journal=Obstetrics and Gynecology |volume=112 |issue=2 Pt 1 |pages=320–24 |year=2008 |month=August |pmid=18669729 |doi=10.1097/AOG.0b013e31817e8acc}}</ref> Note that many of these women go through one or more pregnancies with no difficulties, while others may repeatedly have pregnancy complications, and still others may develop clots within weeks of becoming pregnant. |
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Revision as of 15:30, 2 July 2013
| Factor V Leiden | |
|---|---|
| Specialty | Hematology  |
 | This Introduction may be too technical for most readers to understand. (February 2013) |
Factor V Leiden[1] is an inherited disorder of blood clotting. It is a variant of human factor V that causes a hypercoagulability disorder. In this disorder, the Leiden variant of factor V cannot be inactivated by activated protein C.[2] Factor V Leiden is the most common hereditary hypercoagulability disorder amongst Eurasians.[3][4][5] It is named after the city Leiden (Netherlands), where it was first identified in 1994 by Prof R. Bertina et al.[6]
Pathophysiology
In the normal person, factor V functions as a cofactor to allow factor Xa to activate an enzyme called thrombin. Thrombin in turn cleaves fibrinogen to form fibrin, which polymerizes to form the dense meshwork that makes up the majority of a clot. Activated protein C (aPC) is a natural anticoagulant that acts to limit the extent of clotting by cleaving and degrading factor V.
| SNP: rs6025 | |
|---|---|
| Name(s) | Factor V Leiden, Arg506Gln, R506Q, G1691A |
| Gene | Factor V |
| Chromosome | 1 |
| External databases | |
| Ensembl | Human SNPView |
| dbSNP | 6025 |
| HapMap | 6025 |
| SNPedia | 6025 |
| ALFRED | SI001216K |
Factor V Leiden is an autosomal dominant condition that exhibits incomplete dominance and results in a factor V variant that cannot be as easily degraded by aPC (activated Protein C). The gene that codes the protein is referred to as F5. Mutation of this gene—a single nucleotide polymorphism (SNP) is located in exon 10.[7] As a missense substitution it changes a protein's amino acid from arginine to glutamine. Depending on the chosen start the position of the nucleotide variant is either at position 1691 or 1746.[8] It also affects the amino acid position for the variant, which is either 506 or 534. Together with the general lack of nomenclature standard it means that the SNP can be referred to in several ways such as G1691A, c.1691G>A, 1691G>A, c.1746G>A, p.Arg534Gln, Arg506Gln, R506Q or rs6025. Since this amino acid is normally the cleavage site for aPC, 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.
The excessive clotting that occurs in this disorder is almost always restricted to the veins, where the clotting may cause a deep vein thrombosis (DVT). If the venous clots break off, these clots can travel through the right side of the heart to the lung where they block a pulmonary blood vessel and cause a pulmonary embolism. It is extremely rare for this disorder to cause the formation of clots in arteries that can lead to stroke or heart attack, though a "mini-stroke", known as a transient ischemic attack, is more common . Given that this disease displays incomplete dominance, those who are homozygous for the mutated allele are at a heightened risk for the events detailed above versus those that are heterozygous for the mutation.
Epidemiology
Studies have found that about 5 percent of Caucasians in North America have factor V Leiden. The condition is less common in Hispanics and African-Americans and is extremely rare in people of Asian descent.
Up to 30 percent of patients who present with deep vein thrombosis (DVT) or pulmonary embolism have this condition. 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 (heterozygous) increases by fourfold to eightfold the chance of developing a clot. People who inherit two copies of the mutation (homozygous), one from each parent, may have up to 80 times the usual risk of developing this type of blood clot.[9] 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 between 4 in 1,000 to 8 in 1,000. Having two copies of the mutation may raise the risk as high as 80 in 1,000. It is unclear whether these individuals are at increased risk for recurrent venous thrombosis. While only 1 percent of people with factor V Leiden have two copies of the defective gene, these homozygous individuals have a more severe clinical condition. The presence of acquired risk factors for venous thrombosis—including smoking, use of estrogen-containing (combined) forms of hormonal contraception use, and recent surgery—further increase the chance that an individual with the factor V Leiden mutation will develop DVT.
Women with factor V Leiden have a substantially increased risk of clotting in pregnancy (and on estrogen-containing birth control pills or hormone replacement) in the form of deep vein thrombosis and pulmonary embolism. They also may have a small increased risk of preeclampsia, may have a small increased risk of low birth weight babies, may have a small increased risk of miscarriage and stillbirth due to either clotting in the placenta, umbilical cord, or the fetus (fetal clotting may depend on whether the baby has inherited the gene) or influences the clotting system may have on placental development.[10] Note that many of these women go through one or more pregnancies with no difficulties, while others may repeatedly have pregnancy complications, and still others may develop clots within weeks of becoming pregnant.
Diagnosis
Suspicion of factor V Leiden being the cause for any thrombotic event should be considered in any caucasian patient below the age of 45, or in any person with a family history of venous thrombosis.
There are a few different methods by which this condition can be diagnosed. Most laboratories screen 'at risk' patients with either a snake venom (e.g. dilute Russell's viper venom time) based test or an aPTT based test. In both methods, the time it takes for blood to clot is prolonged in the presence of the factor V Leiden mutation. This is done by running two tests simultaneously, one test is run in the presence of activated protein C (APC) and the other, in the absence. A ratio is determined based on the two tests and the results signify to the laboratory whether APC is working or not. These are quick, three minute, automated tests that most hospital laboratories can easily perform.
There is also a genetic test that can be done for this disorder. The mutation (a 1691G→A substitution) removes a cleavage site of the restriction endonuclease MnlI, so PCR, treatment with MnlI, and then DNA electrophoresis will give a diagnosis.
See also
References
- ^ also known as Leiden Factor 5 (and sometimes factor VLeiden)
- ^ De Stefano V, Leone G (1995). "Resistance to activated protein C due to mutated factor V as a novel cause of inherited thrombophilia". Haematologica. 80 (4): 344–56. PMID 7590506.
- ^ Ridker PM, Miletich JP, Hennekens CH, Buring JE (1997). "Ethnic distribution of factor V Leiden in 4047 men and women. Implications for venous thromboembolism screening". JAMA. 277 (16): 1305–7. doi:10.1001/jama.277.16.1305. PMID 9109469.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Gregg JP, Yamane AJ, Grody WW (1997). "Prevalence of the factor V-Leiden mutation in four distinct American ethnic populations". American Journal of Medical Genetics. 73 (3): 334–6. doi:10.1002/(SICI)1096-8628(19971219)73:3<334::AID-AJMG20>3.0.CO;2-J. PMID 9415695.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ De Stefano V, Chiusolo P, Paciaroni K, Leone G (1998). "Epidemiology of factor V Leiden: clinical implications". Seminars in Thrombosis and Hemostasis. 24 (4): 367–79. doi:10.1055/s-2007-996025. PMID 9763354.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Bertina RM, Koeleman BP, Koster T; et al. (1994). "Mutation in blood coagulation factor V associated with resistance to activated protein C". Nature. 369 (6475): 64–7. doi:10.1038/369064a0. PMID 8164741.
{{cite journal}}: Explicit use of et al. in:|author=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ "SNP linked to Gene F5". NCBI.
- ^ Jennifer Bushwitz, Michael A. Pacanowski, and Julie A. Johnson (2006-10-11). "Important Variant Information for F5". PharmGKB.
{{cite web}}: CS1 maint: multiple names: authors list (link) - ^ What do we know about heredity and factor V Leiden thrombophilia? http://www.genome.gov/15015167#Q5
- ^ Rodger MA, Paidas M, McLintock C; et al. (2008). "Inherited thrombophilia and pregnancy complications revisited". Obstetrics and Gynecology. 112 (2 Pt 1): 320–24. doi:10.1097/AOG.0b013e31817e8acc. PMID 18669729.
{{cite journal}}: Explicit use of et al. in:|author=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link)
Further reading
External links
- factor+V+Leiden at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Kujovich JL, Goodnight SH (2007-02-17). "Factor V Leiden Thrombophilia". GeneReviews. University of Washington, Seattle. Retrieved 2008-06-20.
{{cite web}}: Cite has empty unknown parameter:|coauthors=(help)
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