Factor V Leiden thrombophilia
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.
Symptoms of factor V Leiden include:
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.
Diagnosis[edit]
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 decreased 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 and the other, in the absence. A ratio is determined based on the two tests and the results signify to the laboratory whether activated protein C is working or not. 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. Other PCR based assays such as iPLEX can also identify zygosity and frequency of the variant.
Management[edit]
As there is no cure yet, treatment is focused on prevention of thrombotic complications. Anticoagulants are not routinely recommended for people with heterozygous factor V Leiden, unless there are additional risk factors present, but are given when such an event occurs.[13][14][15] A single occurrence of deep vein thrombosis or pulmonary embolism in people with factor V Leiden warrants temporary anticoagulant treatment, but generally not lifelong treatment.[13] In addition, temporary treatment with an anticoagulant such as heparin may be required during periods of particularly high risk of thrombosis, such as major surgery.[13][15] People with homozygous factor V Leiden or heterozygous factor V Leiden with additional thrombophilia however should be considered for lifelong oral anticoagulation.[15]
Epidemiology[edit]
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.[16][17] One study also suggested "that the factor V‐Leiden mutation segregates in populations with significant Caucasian admixture and is rare in genetically distant non‐European groups."[18] 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.[19] 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 3 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.[20] 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, 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.[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.