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Prothrombin Gene Mutation 20210A

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    The prothrombin gene mutation is a genetically acquired trait and was first described in 1996.

    Mechanism of Action of Prothrombin Gene Mutation:
    Prothrombin is the precursor to thrombin in the coagulation cascade (see the above diagram). Thrombin is required in order to convert fibrinogen into fibrin, which is the primary goal of the coagulation cascade. The gene has a mutation at position 20210, hence the disorder being referred to as prothrombin mutation 20210.

    The mutation leads to an increased amount of thrombin circulating in the person's blood stream. The exact mechanism by which the prothrombin gene mutation results in a thrombophilic state is unclear. It is thought that the increased amount of circulating prothrombin provides a springboard upon which the clotting cascade can get started and that, in some circumstances, it may run out of control because of that springboard potential.

    Epidemiology of the Prothrombin Gene Mutation:
    The prothrombin gene mutation is seen more commonly in the Caucasian population. About 1-2% of the general population is heterozygous (one copy) for the prothrombin gene mutation. The Prothrombin gene mutation is relatively uncommon in the native populations of India, Korea, Africa and North America. In contrast, in Spain rates of 6% have been reported.

    Risks of the Prothrombin Gene Mutation:
    The overall estimated incidence (annual occurrence) of deep venous thrombosis is 1 episode for every 1000 persons. This does not separate patients who had predisposing conditions from those who do not.

    At this time, there is contradicting evidence regarding the role of the prothrombin gene mutation and arterial thrombosis (stroke, heart attack). Based on these data, for persons with the prothrombin gene mutation, the most important preventive steps for the purposes of arterial disease are controlling other risk factors including: smoking, hypertension (high blood pressure), hyperlipidemia (high cholesterol), obesity and a sedentary lifestyle (limited activity).

    The role of the prothrombin gene mutation and venous thromboembolic events is discussed in the table below. Relative risk is a numerical representation of the effects of a condition or treatment on an individual. If a condition or treatment has a relative risk of 1, patients with the condition have no additional risk or benefit from those without the condition. In the studies used below, a relative risk greater than 1 shows an increased risk. For the table below, a relative risk of 4 means that individuals with that condition are 4 times as likely as similar individuals without the same condition, to develop a venous thrombotic event. Despite the increased risk, it is important to remember that the relative risk is a statistical tool to help guide clinicians and scientists and that individual persons can have increased or decreased risks. Even with a very high relative risk, there is no guarantee that a venous thrombotic event will occur.

    Treatment of the Prothrombin Gene Mutation:
    Treatment of the prothrombin gene mutation depends upon the individual patient's risk of recurrent thromboembolic disease. When one has a venous clot, regardless of what thrombophilic state(s) one may have, that person will receive anticoagulation. This is accomplished by several different medications: 1) heparin, 2) warfarin and 3) low-molecular-weight heparins. These medications are generally used for 3-6 months. At this time, there are no long-term studies discussing the use of long-term anticoagulation in the prothrombin gene mutation. Studies have been done in patients with factor V Leiden (a disorder which has an increased risk of thrombosis relatively similar to the prothrombin gene mutation) and the risk of bleeding from anticoagulation outweighed the potential benefits of anticoagulation. Patients that have had multiple thromboembolic episodes or are at high risk of further episodes (for example, multiple deficiencies) may be started on long-term anticoagulation.

    The use of long-term anticoagulation has risks associated with it (approximately a 3% chance per year of having a major hemorrhage, of which approximately 1/5 are fatal). Beginning long-term anticoagulation is influenced by the patient's overall risk of recurrent thrombosis balanced against the risks associated with long-term anticoagulation on an individual basis.

    Further Information:
    For further information on the other thrombophilic states, please refer to their respective pages. Brief information on the various medications that are discussed above and are regularly used to treat clotting disorders is discussed on the medication pages. A selection of the references used to compile this information is listed on the references page.

    Thrombophilic Status
    Relative Risk of Venous Thrombosis
    Normal 1
    Oral contraceptive (OCP) use 4
    Factor V Leiden, heterozygous 5 to 7
    Factor V Leiden, heterozygous + OCP 30 to 35
    Factor V Leiden, homozygous 80
    Factor V Leiden, homozygous + OCP ??? >100
    Prothrombin Gene Mutation, heterozygous 3
    Prothrombin Gene Mutation, homozygous ??? possible risk of arterial thrombosis
    Prothrombin Gene Mutation, heterozygous + OCP 16
    Protein C deficiency, heterozygous 7
    Protein C deficiency, homozygous Severe thrombosis at birth
    Protein S deficiency, heterozygous 6
    Protein S deficiency, homozygous Severe thrombosis at birth
    Antithrombin deficiency, heterozygous 5
    Antithrombin deficiency, homozygous Thought to be lethal prior to birth
    Hyperhomocysteinemia 2 to 4
    Hyperhomocysteinemia combined with Factor V Leiden, heterozygous 20
    *The terms heterozygous (hetero-different) and homozygous (homo-same) are terms used in genetics. The human genome contains to copies of the information. If the copies are the same, they are homozygous; if the copies are different, they are heterozygous. For example, take a protein called A. The normal genome would code for the protein as AA. This is homozygous for the normal protein. If there is a variation of the protein called a, there are two possible ways to get the a. The genome could be Aa, which is called heterozygous or the genome could be aa, which is called homozygous.