Factor V Leiden (FVL) is a condition in which the individual has a greater risk of developing clots within the blood vessels (thrombosis) due to inability to deactivate clotting factor V. It is caused due to a change or mutation in the gene responsible for expressing Factor V. The mutation is known as ‘prothrombin 20210’ (FVL, 2007). This defect can be transmitted to through the genes, and hence this condition may be herditary.
Unlike, Factor V deficiency, this condition results in hypercoagulability of the blood (in Factor V deficiency, bleeding is a prime manifestation). In the US, FVL is the most frequent hypercoagulability disorder that is hereditary in nature. It is more common in the White Population (about 5%) rather than the African-American (about 1.2 %) (FVL, 2007). The conditions can develop in homozygous (both the defective genes are inherited from both the parents) and in heterozygous (only one gene is inherited from either of the parent) states. However, homozygous expressions of the disease are more severe in terms of thrombosis risk compared to the heterozygosis versions (the risk of thrombosis increases by about 10 times in homozygous compared to heterozygous versions) (FVL, 2007).
The National Human Genome Research Institute is conducting a lot of Research in the field of Factor V Leiden. Currently, a study is being performed to determine the effect of Factor V Leiden in children. An area in which research needs to be conducted is to study the different genetic mutations of Factor V Leiden. Individuals suffering from thrombosis are frequently studied (NHGRI, 2006)
Factor V, which plays a role during clotting, is inactivated by Activated protein C, and this effectively controls clotting and prevent thrombosis within the blood vessels. In Activated Protein C Resistance (APCR), Protein C is not effective in inactivating Factor V, and hence clot formation within the blood vessels occurs. About 95 % of APCR cases develop due to inherited Factor V Leiden. Individuals with FVL have a mutated gene which results in production of an Factor V known as ‘Factor V Leiden’, which responds less frequently to APC. The amino acid number 506 is glutamine rather than arginine (LCA, 2007). The Factor V does not get inactivated by certain enzymes. The long arm of chromosome 1 carries the gene responsible for expressing Factor V (Bauer, 2000). Protein C works by inactivating Factor Va and Factor VIIIa. This process begins by thrombin undergoing conversion to thrombomodulin. The protein gets activated to Activated Protein C once it combines with thrombomodulin, and later combines with protein S which is present on the platelets. The protein C then inactivates Factor Va and Factor VIIIa. Individuals who have Factor V Leiden, are less likely to have the Factor V Leiden degraded by activated protein C, and hence the blood has a higher tendency to clot within the blood vessels (University of Illinois, 2006).
The most common population affected with FVL is the North European population (3 to 7 % have the heterozygous version of the disorder) (LCA, 2007). The disorder also occurs in individuals belonging to Jewish, Arab and Indian Populations. Chinese, Japanese, Africans, Native North Americans, and Mediterranean populations are relatively free from the disorder. Studies conducted suggested that the condition originated some 30, 000 years ago, once the Caucasians, African and Oriental groups began to diversify (Bauer, 2000). In the US population, the Incidences of FVL was higher in Whites (5.27 %) and lower in other groups such as African-Americans (1.23 %), Hispanic-Americans (2.21%), Native-Americans (1.25 %) and Asian-Americans (0.45 %) (Price, 1997). The exact prevalence rate of FVL in Baltimore, Maryland, is not known, but it may be similar to the national prevalence.
Individuals with FVL are at a greater risk of developing clot formation within the blood vessels. At the moment, not much evidence is available to support the role of FVL in the formation of clots within the arteries (that could result in several conditions such as stroke and myocardial infarction). However, individuals with FVL have shown a greater tendency of developing thrombus formation within the veins of the body. In individuals with the heterozygous version of the disorder, the chances of venous thrombosis are 5 to 7 %, whereas in the homozygous version, the chances of developing venous thrombosis are 80 %. The use of birth control pills significantly increases the risk of developing venous thrombosis. In individuals who are heterozygous, the chances are about 30 to 35 %, whereas it is about 100 % in individuals with the homozygous version (University of Illinois, 2006).
Individuals with FVT are at a very high risk of developing deep vein thrombosis or pulmonary embolism. Women are at risk of developing deep vein thrombosis during their pregnancy which could lead to fatal outcomes. The legs are most commonly involved with deep vein thrombosis, but other sites of the body, such as the cerebral veins or the veins that feed the liver could also be affected (NHGRI, 2006). The risk of clots developing is especially high following surgery. Some of the thrombus that forms in the veins may break off and travel into the arteries that carry blood from the heart to the lungs (pulmonary arteries). The individual develops several symptoms such as cough, severe chest pain, difficulty in breathing, elevated heart beat, bluish discoloration of the skin, leg pain, etc (Blaivas, 2005).
The diagnosis of FVT is made based on the history (especially the family history), symptoms, signs, physical examination, blood tests, genetic tests and other tests. A detailed family history is conducted to determine if any hypercoagubility disorder exists in the family. Genetic tests are required to determine the presence of the faulty gene. The genome (DNA) of mononuclear cells is studied using highly sensitive and specific molecular techniques such as Polymerase chain Reaction. Insitu hybridization can also be used to study the DNA. Coagulation Essays can be utilized to determine the APC resistance and provide an idea of FVL. This is a cost-effective way of determining the presence of FVL (Bauer, 2000). Thrombosis can be determined using ultrasound, X-rays, or venography.
FVT is treated by administering anticoagulants in order to treat first-hand thrombo-embolism c events. Individuals with recurrent thromobo-embolism events or those who face higher chances of risk may require administration of anticoagulants for a longer period. Heparin and Warfarin can be utilized in the treatment. Individuals who are asymptomatic and do not have any risk factors, usually do not require any form of treatment. Pregnant women should not be administered Warfarin. Individuals may require preventive treatment of FVL during high-risk periods such as pregnancy or after surgery (Kujovich, 2007). Pregnant women are usually administered heparin and are advised to wear specialized stockings to reduce the risk of deep vein thrombosis in the legs (Davey, 2007). The individual may have to follow certain measures to prevent clots from developing. They should avoid sitting, standing or immobility for long periods of time. Regular exercises are required to prevent blood from stagnating in the limbs. Smoking should be reduced and women consuming birth control pills should determine their Factor V status. Individuals who are overweight should try to reduce their body weight (Davey, 2007). The outcome of FVL is good provided that adequate precautions are taken. As the age increases, the risk of thrombo-embolism also rises, making the individual at a higher risk at arriving at fatal complications.
Factor V Leiden is an inherited disorder in which the individual develops another form of Factor V, which is resistant to inactivation from Activated protein C. Such individuals are prone to suffer from thrombo-embolism events. The veins are usually involved, especially the veins of the legs. Two types of FVL exists, namely heterozygous (in which only one of the defective gene is inherited from either of the parent) or homozygous (in which both the defective genes are inherited from both the parents). The disease is more severe in individuals with the homozygous version. Individuals consuming birth control pills, pregnant women, individuals who follow a sedentary lifestyle, obesity, smoking, etc, act as risk factors of the disorder. Individual with FVL are at a risk of developing thrombo-embolism events such as deep vein thrombosis and pulmonary embolism. The condition is treated by administering anticoagulants and taking a few precautions.
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