Factor V Leiden
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226047835
2008-07-16T16:24:31Z
71.62.136.66
/* Pathophysiology */
{{Refimprove|date=April 2008}}
{{Infobox_Disease
| Name = Factor V Leiden
| Image =
| Caption =
| DiseasesDB = 154
| ICD10 =
| ICD9 = {{ICD9|289.81}}
| ICDO =
| OMIM =
| MedlinePlus =
| eMedicineSubj =
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}}
'''Factor V Leiden''' (sometimes ''Factor V<sub>Leiden</sub>'') is the name given to a variant of human [[factor V]] that causes a [[thrombophilia|hypercoagulability]] disorder. In this disorder the Leiden variant of [[factor V]], cannot be inactivated by [[activated protein C]].<ref name="pmid7590506">{{cite journal | author = De Stefano V, Leone G | title = Resistance to activated protein C due to mutated factor V as a novel cause of inherited thrombophilia | journal = Haematologica | volume = 80 | issue = 4 | pages = 344–56 | year = 1995 | pmid = 7590506 | doi = | url = http://www.haematologica.org/cgi/content/abstract/80/4/344 | issn = }}</ref> Factor V Leiden is the most common [[hereditary]] hypercoagulability [[disease|disorder]] amongst [[Eurasia]]ns.<ref name="pmid9109469">{{cite journal | author = Ridker PM, Miletich JP, Hennekens CH, Buring JE | title = Ethnic distribution of factor V Leiden in 4047 men and women. Implications for venous thromboembolism screening | journal = JAMA | volume = 277 | issue = 16 | pages = 1305–7 | year = 1997 | pmid = 9109469 | doi = | url = | issn = }}</ref><ref name="pmid9415695">{{cite journal | author = Gregg JP, Yamane AJ, Grody WW | title = Prevalence of the factor V-Leiden mutation in four distinct American ethnic populations | journal = Am. J. Med. Genet. | volume = 73 | issue = 3 | pages = 334–6 | year = 1997 | month = December | pmid = 9415695 | doi = 10.1002/(SICI)1096-8628(19971219)73:3<334::AID-AJMG20>3.0.CO;2-J | url = }}</ref><ref name="pmid9763354">{{cite journal | author = De Stefano V, Chiusolo P, Paciaroni K, Leone G | title = Epidemiology of factor V Leiden: clinical implications | journal = Semin. Thromb. Hemost. | volume = 24 | issue = 4 | pages = 367–79 | year = 1998 | pmid = 9763354 | doi = | url = | issn = }}</ref> It is named after the city [[Leiden]] ([[The Netherlands]]), where it was first identified in [[1994]] by Prof R. Bertina ''et al''.<ref name="pmid8164741">{{cite journal |author=Bertina RM, Koeleman BP, Koster T, ''et al'' |title=Mutation in blood coagulation factor V associated with resistance to activated protein C |journal=Nature |volume=369 |issue=6475 |pages=64–7 |year=1994 |pmid=8164741 |doi=10.1038/369064a0}}</ref>
==Pathophysiology==
In the normal person, factor V functions as a [[cofactor]] to allow [[factor X]] to activate an [[enzyme]] called [[thrombin]]. Thrombin in turn cleaves [[fibrinogen]] to [[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.
{{Infobox Single nucleotide polymorphism
| rsid = 6025
| name_1 = Factor V Leiden
| name_2 = Arg506Gln
| name_3 = R506Q
| name_4 = G1691A
| gene = F5
| chromosome = 1
| alfred = SI001216K
}}
Factor V Leiden is an [[autosomal dominant]] condition in which the coagulation factor cannot be destroyed by aPC.
The [[gene]] that codes the protein is refered to a ''F5''.
[[Mutation]] of this [[gene]]—a [[single nucleotide polymorphism]] (SNP) refered to as G1691A or rs6025—changes the [[protein]]'s 506th [[amino acid]] from [[arginine]] to [[glutamine]], thus the SNP is also called Arg506Gln.
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 excess fibrin generation 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 [[heart]] to the [[lung]], where they block a [[pulmonary blood vessel]] and cause a [[pulmonary embolism]]. Women with the disorder have an increased risk of miscarriage and stillbirth. It is extremely rare for this disorder to cause the formation of clots in arteries that can lead to [[stroke]] or [[myocardial infarction|heart attack]], though rare a "mini-stroke" known as a [[transient ischemic attack]] is more common .
==Epidemiology==
Studies have found that about 5% of caucasians in North America have factor V Leiden. The disease is less common in Hispanics and African-Americans and is extremely rare in people of Asian descent.
Up to 30% of patients who present with [[deep vein thrombosis]] (DVT) or [[pulmonary embolism]] have this condition. Factor V Leiden doubles the risk that a person will have a DVT during their life, but it is unclear whether these individuals are at increased risk for recurrent a venous thrombosis. While only 1% 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.
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 have an increased risk of [[preeclampsia]], as well as [[miscarriage]] and [[stillbirth]] due to clotting in the placenta, umbilical cord, or the fetus (fetal clotting may depend on whether the baby has inherited the gene). Note that many of these women go through one or more pregnancies with no difficulties, while others may miscarry over and over again, 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 white patient below the age of 45, or in any person with a family history of venous thrombosis.
This disease can be diagnosed by watching the [[aPTT]] (the time it takes for blood to clot) as activated protein C is added. With a normal patient, adding aPC increases the aPTT. In patients with factor V Leiden, adding aPC will barely affect the time it takes for blood to clot.
There is also a simple 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 simple [[PCR]], treatment with ''MnlI'', and then [[DNA electrophoresis]] will give a quick diagnosis.
==References==
{{Reflist|2}}
== External links ==
* {{MeshName|factor+V+Leiden}}
* {{cite web | url = http://www.genetests.org/profiles/factor-v-leiden/index.html | title = Factor V Leiden Thrombophilia | author = Kujovich JL, Goodnight SH | authorlink = | coauthors = | date = 2007-02-17 | format = | work = GeneReviews | publisher = University of Washington, Seattle | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = 2008-06-20}}
* {{cite web | url = http://www.fvleiden.org/ | title = Thrombophilia Awareness Project | author = Smith DO | authorlink = | coauthors = | date = 2008-05-12 | format = | work = | publisher = | pages = | language = | archiveurl = | archivedate = | quote = Information for those living with thrombophilia | accessdate = 2008-06-20}}
{{hematology}}
[[Category:Blood proteins]]
[[Category:Hematology]]
[[Category:Single nucleotide polymorphisms]]
[[de:Faktor-V-Leiden]]
[[fr:Thrombophilie par mutation du facteur V]]
[[nl:Factor V Leiden]]
[[pl:Czynnik V Leiden]]