Factor V Leiden

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Factor V Leiden thrombophilia
SpecialtyHematology

Factor V Leiden (rs6025 or F5 p.R506Q

venous thromboembolisms, people with one copy of this gene have not been found to have shorter lives than the general population.[7] It is an autosomal dominant genetic disorder with incomplete penetrance
.

Signs and symptoms

The symptoms of factor V Leiden vary among individuals. There are some individuals who have the F5 gene and who never develop thrombosis, while others have recurring thrombosis before the age of 30 years. This variability is influenced by the number of F5 gene (chromosome 1) mutations a person has, the presence of other gene alterations related to blood clotting, and circumstantial risk factors, such as surgery, use of oral contraceptives and pregnancy.[citation needed]

Symptoms of factor V Leiden include:[citation needed]

  • Having a first DVT (deep vein thrombosis) or PE (pulmonary embolism) before age 50.
  • Having recurring DVT or PE.
  • Having venous thrombosis in unusual sites in the body such as the brain or the liver.
  • Having a DVT or PE during or right after pregnancy.
  • Having a history of unexplained pregnancy loss in the second or third trimester.
  • Having a DVT or PE and a strong family history of venous thromboembolism.

The use of hormones, such as oral contraceptive pills (OCPs) and hormone replacement therapy (HRT), including estrogen and estrogen-like drugs taken after menopause, increases the risk of developing DVT and PE. Healthy women taking OCPs have a three- to four-fold increased risk of developing a DVT or PE compared with women who do not take OCP. Women with factor V Leiden who take OCPs have about a 35-fold increased risk of developing a DVT or PE compared with women without factor V Leiden and those who do not take OCPs. Likewise, postmenopausal women taking HRT have a two- to three-fold higher risk of developing a DVT or PE than women who do not take HRT, and women with factor V Leiden who take HRT have a 15-fold higher risk. Women with heterozygous factor V Leiden who are making decisions about OCP or HRT use should take these statistics into consideration when weighing the risks and benefits of treatment.[citation needed]

Pathophysiology

In the normal pathway, factor V functions as a

clot. Activated protein C is a natural anticoagulant that acts to limit the extent of clotting by cleaving and degrading factor V.[citation needed
]

SNP: rs6025
Name(s)Factor V Leiden, Arg506Gln, R506Q, G1691A
HapMap
6025
SNPedia6025
ALFREDSI001216K

Factor V Leiden is an

missense substitution of amino acid R to amino acid Q, it changes the 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.[9] It also affects the amino acid position for the variant, which is either 506 or 534. (Together with the general lack of nomenclature standard, this variance 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 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.[10]

The excessive clotting that occurs in this disorder is almost always restricted to the

heterozygous for the mutation.[12]

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.

DNA electrophoresis will give a diagnosis. Other PCR based assays such as iPLEX can also identify zygosity and frequency of the variant.[citation needed
]

Management

As there is no cure yet, treatment is focused on prevention of thrombotic complications.

homozygous factor V Leiden or heterozygous factor V Leiden with additional thrombophilia however should be considered for lifelong oral anticoagulation.[15]

Epidemiology

Studies have found that about 5 percent of Caucasians in North America have factor V Leiden. Data have indicated that prevalence of factor V Leiden is greater among Caucasians than minority Americans.

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, and recent surgery—further increase the chance that an individual with the factor V Leiden mutation will develop DVT.[citation needed
]

Women with factor V Leiden have a substantially increased risk of clotting in

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.[21] 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.[citation needed
]

See also

References

  1. PMID 31676865. Archived from the original
    (PDF) on 2020-01-28. Retrieved 2020-01-28.
  2. PMID 7590506
    .
  3. PMID 9109469
    .
  4. PMID 9415695
    .
  5. S2CID 45534038
    .
  6. S2CID 4314040
    .
  7. PMID 21116184
    .
  8. ^ "SNP linked to Gene F5". NCBI.
  9. ^ Jennifer Bushwitz; Michael A. Pacanowski & Julie A. Johnson (2006-10-11). "Important Variant Information for F5". PharmGKB. Archived from the original on 2011-07-27. Retrieved 2008-09-10.
  10. S2CID 9556602
    .
  11. PMID 10828239
    .
  12. ^ "Factor V Leiden Mutation – Homozygous" (PDF).
  13. ^
    PMID 12707252
    .
  14. PMID 26316770
    .
  15. ^
    PMID 8790269
    .
  16. ^ Ridker, et al. "Ethnic distribution of factor V Leiden in 4047 men and women". Supra.
  17. ^ Gregg, et al. "Prevalence of the factor V-Leiden mutation in four distinct American ethnic populations". Supra.
  18. ^ Id.
  19. ^ What do we know about heredity and factor V Leiden thrombophilia? http://www.genome.gov/15015167#Q5
  20. ^ "Factor V Leiden thrombophilia: MedlinePlus Genetics".
  21. PMID 18669729
    .

Further reading

External links

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