Hereditary Thrombophilia

Background

Hereditary thrombophilia is the increased tendency to develop blood clots in blood vessels. Blood is designed to flow freely round the body and not obstruct blood vessels. At the time of a cut, however, blood thickens due to local activation of the chemicals responsible for clotting and becomes sticky around the injured area forming a semi-solid mass thrombus (blood clot). This prevents bleeding and limits blood loss while the repair of the blood vessels takes place. In thrombophilia, clotting most often occurs within an unbroken vessel at an inappropriate time and place.

Blood clots may form within all blood vessels, but typically occur in the large or important vessels in the brain, heart, lungs, legs and arms. Clots in the leg or the arm can usually be detected by ultra-sound examination. In addition, clots can be detected by X-ray examination by injecting a substance into the blood to make the clot stand out. A blood clot in the lung is more difficult to diagnose. A radioactive substance may be used to test for a mismatch between the distribution pattern of blood flowing in the vessels and of the air filled spaces in the lungs. Such a mismatch would indicate the presence of a clot.

Credits

Medical text written February 2002 by Contact a Family. Approved February 2002 by Professor F Cotter. Last updated January 2010 by Professor F Cotter, Professor of Experimental Haematology, Department of Medical Oncology, Barts and the London School of Medicine and Consultant Haematologist, Barts and the London NHS Trust, London, UK.

What are the symptoms?

The symptoms can be varied and depend on the site of the clot in the body. Clots interfere with normal blood flow by completely or partly obstructing vessels. This leads to a build-up of blood before the clot (in an artery) or behind the clot (in a vein) causing pain and swelling of the tissue around the area. Clots deprive tissues and organs of oxygen and nutrition and may cause permanent damage particularly if the clot obstructs a vital organ, such as in certain parts of the brain or heart. They may grow very quickly and can break apart sending small pieces of the clot (known as emboli) through the blood stream. These emboli can then become lodged in smaller vessels distant from the clot of origin. An emboli lodging within vessels of the lung is known as a pulmonary embolus. By blocking the blood to the lung and depriving the body of oxygen, they may be rapidly life threatening. An emboli lodging in brain vessels can cause a stroke. These are serious conditions which may be associated with a high risk of disablement. Consequently, thrombotic events may require immediate medical attention and appropriate treatment.

Factor V Leiden

In the most common form of inherited thrombophilia, factor V Leiden, the leg may become swollen, painful and red. In some individuals, part of the clot may be dislodged and flow to the lung (pulmonary embolism) which may make breathing difficult. Depending on the size of the blood clot, some individuals may experience severe respiratory difficulty whereas in others breathing problems may be barely noticeable. In very rare cases, a clot might occur in the arm, brain, or liver. Since clots associated with factor V Leiden form in the veins (which take blood to the heart), there is no increased risk of coronary occlusion. However, pregnancy loss and other obstetric complications may occur at an increased rate in women with factor V Leiden. It is important to look for the presence of factor V Leiden in women who experience recurrent miscarriages as it can be treated to reduce the risk of these events occurring.

Factor V Leiden is associated with a change in the factor V gene, otherwise known as factor V Leiden mutation. The factor V gene codes for a coagulant protein. A ‘Leiden’ mutation (or change) in the factor V gene may lead to an increased tendency to develop an inappropriate blood clot. The first blood clot usually occurs in adulthood (approximately 45 years) but may occur in premature babies, neonates and pregnant women. The risk of developing a clot is thought to increase with age. Factor V Leiden is associated with both deep and superficial blood clots in the legs (venous thromboses).

What are the causes?

The clotting process (otherwise known as haemostasis) functions as a careful balance between flowing and stopping; and between clotting and dissolving/reabsorbing clots. The consistency of blood is regulated and maintained by the careful balance of a number of different proteins; some of which are involved in coagulation (clot forming) and some of which are involved in the prevention of clot formation and anticoagulation or fibrinolysis (dissolving of formed clots). Thrombophilia may occur in association with abnormalities in either coagulation or anticoagulation proteins.

Specific genes are known to code for coagulation and anticoagulation proteins. Individuals who inherit changes (or mutations) in these genes may have an increased risk or ‘predisposition’ to developing thrombophilia compared to the rest of the population. However, in certain individuals there may only be a small increased risk to health. Other people who have inherited a predisposition to thrombophilia will not experience any symptoms and will remain healthy and unaffected. In particular, the predisposition to forming a thrombosis may be of relevance to our lifestyles as for example the increased risk to air travellers.

How is it diagnosed?

Doctors may suspect an inherited predisposition to blood clotting in individuals who have a blocked blood vessel at a young age, or have recurrent thromboses, or have a strong family history of clotting disorders (such as stroke, pulmonary embolism, or deep vein thrombosis). A diagnosis may be made by screening for inherited blood-clotting factors which are known as factor V Leiden and prothrombin gene mutation. Screening for these genetic changes should form part of the routine investigations for individuals who present with thromboses.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
Factor V Leiden is inherited as an autosomal dominant trait. However, in some cases, factor V Leiden may be increased as an autosomal recessive trait. This is associated with a greater risk of venous thrombosis.

Prenatal diagnosis 
Prenatal testing is not routinely available.

Prothrombin gene mutations

The prothrombin gene is responsible for the production of a protein, which helps the blood to clot. A change (or mutation) in the prothrombin gene may lead to an increased tendency to develop an inappropriate blood clot. Clinically this may manifest in a similar manner to patients with factor V Leiden. Again, the risk of thrombosis is heightened in pregnancy. This condition is associated with an increased risk of venous thrombosis, blood clots in the legs and lungs (pulmonary embolism), but most frequently in the deep veins of the lower extremities. Blood clots may occur in the head (cerebral vein thrombosis). However, clots may also occur in unusual sites, particularly cerebral sinus vein thrombosis.

Inheritance patterns
Prothrombin is inherited as an autosomal recessive trait. Individuals with a mutation in both prothrombin genes, one on each chromosome, are called homozygous and they appear more likely than heterozygotes (one mutated gene and one normal gene) to develop thrombosis.

Prenatal diagnosis
Prenatal testing is not routinely available.

Is there support?

There is no support group for hereditary thrombophilia in the UK. Cross referrals to other entries in Contact’s directory are intended to provide relevant support for those particular features of the disorder. Organisations identified in those entries do not provide support specifically for hereditary thrombophilia.

Families can use Contact’s freephone helpline for advice, information and, where possible, links to other families. To meet other families with disabled children, join Contact’s closed (private) Facebook group.

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