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Chapters

0:00 Introduction
0:47 Causes of Factor V Leiden
1:26 Signs and symptoms of Factor V Leiden
2:19 Treatment for Factor V Leiden





Factor V Leiden (rs6025 or F5 p.R506Q[1]) 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.[2] Factor V Leiden is the most common hereditary hypercoagulability (prone to clotting) disorder amongst ethnic Europeans.[3][4][5] It is named after the Dutch city of Leiden, where it was first identified in 1994 by Rogier Maria Bertina under the direction of (and in the laboratory of) Pieter Hendrick Reitsma.[6] Despite the increased risk of venous thromboembolisms, people with one copy of this gene have not been found to have shorter lives than the general population.[7]
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 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 or PE before 50 years of age.
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 cofactor to allow factor Xa to activate prothrombin, resulting in the enzyme 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 is a natural anticoagulant that acts to limit the extent of clotting by cleaving and degrading factor V.[citation needed]
SNP: Factor V Leiden
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