Factor V Leiden thrombophilia

Factor V Leiden thrombophilia is an inherited disorder of blood clotting. Factor V Leiden is the name of a specific mutation that results in thrombophilia, or an increased tendency to form abnormal blood clots in blood vessels. People who have the factor V Leiden mutation are at somewhat higher than average risk for a type of clot that forms in veins, such as the deep veins of the legs (deep venous thrombosis), or a clot that travels through the bloodstream and lodges in the lungs (pulmonary embolism). Most people with the factor V Leiden mutation never develop abnormal blood clots, however.

The factor V Leiden mutation is associated with a somewhat increased risk of pregnancy loss (miscarriage), and some research suggests that it may also increase the risk of other complications during pregnancy. These complications may include pregnancy-induced high blood pressure (preeclampsia), slow fetal growth, and early separation of the placenta from the uterine wall (placental abruption). It is important to note, however, that most women with the factor V Leiden mutation have normal pregnancies.

Factor V Leiden is the most common inherited form of thrombophilia. Between 3 percent and 8 percent of the Caucasian (white) population in the United States and Europe carry one copy of the factor V Leiden mutation in each cell, and about 1 in 5,000 people have two copies of the mutation. The mutation is less common in other populations.

Mutations in the F5 gene cause factor V Leiden thrombophilia.

The F5 gene plays a critical role in the formation of blood clots in response to injury. The protein made by the F5 gene, coagulation factor V, 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.

Other factors also increase the risk of blood clots in people with the factor V Leiden mutation. These factors include increasing age, obesity, trauma, surgery, smoking, the use of oral contraceptives (birth control pills) or hormone replacement therapy, and pregnancy. The combination of the factor V Leiden mutation and mutations in other genes involved in blood clotting can also influence risk.

Read more about the F5 gene.

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 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 people per year in the general population, the presence of one copy of the factor V Leiden mutation increases that risk to 4 to 8 in 1,000, and having two copies of the mutation may raise the risk as high as 80 in 1,000.