Thrombophilia

What is thrombophilia?

Thrombophilia is a condition where the blood forms clots more easily than normal, which can lead to unwanted blood clots in the body. There are different kinds of thrombophilia.

What causes thrombophilia?

The body has a natural clotting process in the blood, which is altered in thrombophilia.

The normal clotting process is called ‘haemostasis’. It helps to stop bleeding if there is an injury. When a blood vessel is injured, the clotting process is triggered, and this is called the ‘clotting cascade’. It is a chain reaction of different chemicals in the blood, which are called ‘clotting factors’. The clotting cascade makes the blood solidify into a clot, which sticks to the injured part of the blood vessel. Small particles in the blood called 'platelets' also help to form the clot.

There are also natural chemicals in the blood which act against the clotting system, to stop the blood clotting too much.

Thrombophilia occurs if the normal balance of the clotting system is upset. There may be too much of a clotting factor, or too little of a factor that opposes clotting.

Thrombophilia can cause unwanted blood clots. This does not mean that every person with thrombophilia will get a blood clot, but it means that you may have a higher risk than normal of getting clots. The amount of extra risk will depend on the type of thrombophilia that you have.

What are the different types of thrombophilia?

Thrombophilias can be classified into 'inherited' or 'acquired'. The inherited ones are genetic, and may be passed on from parent to child. The acquired ones mean anything else other than genes which increases the clotting process.

The different types of thrombophilias are explained in more detail in the last section.

What are the symptoms of thrombophilia?

There are no symptoms unless the thrombophilia results in a clot. Many people with thrombophilia do not get clots and have no symptoms at all. If you have an inherited type of thrombophilia, your family history may be a 'symptom', if close relatives have had blood clots at a relatively young age (under age 40).

What are the symptoms of blood clots?

There are two types of blood clots: clots in arteries and clots in veins. Arteries are blood vessels that take blood from the heart to the organs and tissues of the body. Veins are blood vessels that take blood back to the heart.

• Pain and swelling in a leg. This occurs if you have a blood clot in a large vein in a leg. This is commonly known as a 'deep vein thrombosis' or 'DVT'.
• The clot may travel to the heart and on into a lung, causing a 'pulmonary embolus' or 'PE'. Possible symptoms are chest pain, pain on deep breathing, shortness of breath or rarely, collapse.
• Some types of thrombophilia can cause clots in unusual sites, such as the brain, gut or liver. This can cause symptoms in the head or the abdomen (tummy). Clots in liver veins are called 'Budd-Chiari syndrome'.

See separate leaflets 'Deep Vein Thrombosis (DVT)' and 'Pulmonary Embolism'.

Clots in arteries can occur with some types of thrombophilia. Clots in arteries can cause a stroke, a heart attack or problems with the placenta during pregnancy. So the possible symptoms of artery clots due to thrombophilia are:

• Having a stroke at a relatively young age
• Repeated miscarriages
• Pregnancy problems: pre-eclampsia, reduced fetal growth or rarely fetal death
• A heart attack

(But note that all of these can be due to causes other than thrombophilia.)

How is thrombophilia diagnosed?

Thrombophilia may be suspected if you have a family history of blood clots at a young age (under 45 years), or if you develop a blood clot which would not be expected, given your age and general health.

What are the tests for thrombophilia?

Thrombophilia is diagnosed by blood tests. A sample of blood is taken, and a number of different tests will be done on it, to check different parts of the clotting process.

Usually, the tests are done in two stages. The first test is a ‘thrombophilia screen’ which is some basic clotting tests. If the results of this suggest that thrombophilia is possible, then another blood sample will be taken for more detailed tests. You may be referred to a haematologist (a doctor specialising in blood conditions). The doctor will usually ask about your history and family history, which will help with interpreting the test results.

Can all thrombophilias be diagnosed on tests?

It is likely that there are some kinds of thrombophilia which we cannot yet identify or test for. This is because there are some patients or families who get more blood clots than would normally be expected, yet test negative on the thrombophilia tests. In this situation, you might be advised to have treatment as for thrombophilia, even if you do not have a definite diagnosis.

Who should be tested for thrombophilia?

Current guidelines suggest that thrombophilia testing should be considered in the following situations:

• Venous thrombosis or pulmonary embolus occurring under age of 45 years.
• Repeated episodes of venous thrombosis or pulmonary embolus or thrombophlebitis (inflamed veins).
• Venous thrombosis in an unusual site (eg abdomen or brain).
• Unexplained blood clots in newborn babies.
• Skin necrosis (patches of skin loss due to clots in the skin).
• A blood clot in an artery occurring under the age of 40 years.
• Relatives of patients with thrombophilia.
• Patients with clear family history of venous thrombosis.
• Certain blood test results: an unexplained 'prolonged activated partial thromboplastin time' (an abnormal result on a certain type of blood clotting test).
• Some patients with other medical conditions: recurrent miscarriage or fetal death, idiopathic thrombocytopenic purpura (a condition affecting blood platelets), or systemic lupus erythematosus ('lupus') - because these can sometimes be linked to thrombophilia.

What is the treatment for thrombophilia?

The first step is for you and your doctor to consider how much risk there is of you getting an unwanted clot. This risk depends on a combination of things, such as:

• What type of thrombophilia you have.
• Your age, weight, lifestyle and other medical conditions.
• Whether you are pregnant or have recently given birth.
• Whether you have already had a blood clot.
• Your family history - whether close relatives have had a blood clot.

This information will help your doctor to assess how much risk you have of getting a clot, and what type of clot could occur. Then you and your doctor can discuss the pros and cons of taking treatment, and if needed, what type of treatment to take.

Possible treatments for thrombophilia are:

Low dose aspirin

This inhibits the action of platelets, so can prevent clots. It may also help prevent miscarriage or pregnancy problems, in some types of thrombophilia.

Anticoagulant treatment

Anticoagulant medication slows down the clotting process. It is commonly used to prevent or treat venous thrombosis and pulmonary embolism. In thrombophilia, anticoagulant medication may be advised if:

• You have had a clot, to prevent another one.
• You have not had a clot, but have a very high risk of getting one.
• You have a temporary situation that puts you at high risk of a clot - this may be the case if you are pregnant, within 6 weeks after childbirth, or are immobile for a long period.

There are two types of anticoagulant: heparin and warfarin. They work by slowing down the clotting process in the blood. Heparin is taken as an injection once or twice daily. Warfarin is taken as a tablet once daily.

With warfarin treatment, the dose has to be adjusted on an individual basis. You will need a blood test which checks the clotting speed, and then the dose is adjusted according to the result. This can be done in an outpatient clinic, or sometimes by your GP. Heparin doses may need to be adjusted in a similar way, or may be taken as a fixed dose, depending on the type of heparin and on the dose that is prescribed.

Treatment in pregnancy

If you are pregnant or planning a pregnancy, discuss this your doctor, and tell your midwife and obstetrician about the thrombophilia. Treatment for thrombophilia may be different in pregnancy because:

• Some women with certain types of thrombophilia are advised to take low-dose aspirin while pregnant, to help prevent miscarriage or pregnancy problems.
• The pregnancy itself increases the risk of a venous thrombosis - this applies to the whole pregnancy and especially to the 6 weeks after childbirth. So you may be advised to start anticoagulant treatment while pregnant or after childbirth. This will depend on the type of thrombophilia and your medical history.
• If you were taking warfarin, you will normally be advised to change to heparin instead. This is because heparin is safer for the unborn baby (there is a significant chance that warfarin could cause fetal abnormalities). Both heparin and warfarin are safe for breastfeeding.

Prevention of venous thrombosis (DVT)

Certain situations can put you at 'high risk' of venous thrombosis temporarily, and in these situations you may be advised to take extra treatment for a while. Examples are pregnancy and after childbirth, severe illness, major surgery, or anything which immobilises you, such as travel or an operation. Special stockings such as flight socks or compression stockings may also be advised to help prevent a DVT.

General advice for people with thrombophilia

• If you are having any treatment or surgery, tell your doctor/nurse/pharmacist about the thrombophilia.
• Be aware of the warning symptoms of blood clots - get medical help immediately if you suspect one (see above for symptoms).
• Avoid dehydration by drinking adequate amounts of fluid - dehydration can contribute to blood clots.
• Keep active, and avoid being immobile for long periods - immobility helps cause venous thrombosis.
• Caution with medication: some medications increase the risk of blood clots. For example, the combined oral contraceptive pill or patch and hormone replacement therapy. You may be advised to avoid certain medications, or to change to one which does not affect clotting.
• Keep to a healthy weight - being overweight increases the risk of a venous thrombosis.
• To keep blood vessels healthy (arteries in particular), do not smoke. This is important if you have thrombophilia of a type that can cause artery clots, as smoking promotes clots in arteries.
• Eat a balanced diet, including fresh fruit and vegetables, to help keep blood vessels healthy.

What are the complications of thrombophilia - and what is the outlook?

Often there are no complications. Many forms of thrombophilia are mild in any case, so that many people with thrombophilia have no problems from their condition. Also, treatment can successfully prevent complications in many cases.

If blood clots do occur there may be serious complications. A pulmonary embolus, stroke, heart attack or a clot in the brain or abdomen may all cause severe illness, or if the clot is large enough they may be fatal. Early treatment can be life-saving and reduces complications. So it is important to be aware of symptoms and get treatment immediately if you suspect any kind of blood clot.

As mentioned above, some types (not all) of thrombophilia may increase the chance of problems in pregnancy. Your doctor can advise - it will depend on the type of thrombophilia and also varies between individuals. However, many women with thrombophilia have successful pregnancies.

There may also be complications due to treatment. Aspirin, heparin and warfarin can have side-effects, mainly unwanted bleeding, such as internal bleeding from the stomach lining. For this reason, it is important for you and your doctor to weigh up the pros and cons of taking treatment, taking into account your individual situation and preferences.

Testing relatives

If you or your family have an inherited (genetic) form of thrombophilia, you may be asked to consider tests for yourself or your close relatives, to see if you or others in the family have the same condition. In most cases, tests are not required for children, because children don't usually get blood clots. So the child can normally wait until their teenage years before considering thrombophilia tests.

What are the different types of thrombophilia?

This section explains the more common types of thrombophilia, although it does not cover every condition.

Inherited thrombophilias

Factor V Leiden

This is pronounced “factor 5 lyden”. It is fairly common in people of European origin, and about 1 in 20 Europeans have the factor V Leiden gene. This gene affects the factor V part of the clotting cascade, making the clotting process go on longer. It increases the risk of venous thrombosis by about eight times - that is still a relatively low risk, so most people with factor V Leiden do not develop clots. Some people inherit two factor V Leiden genes - one gene from each parent (known as ‘homozygous Factor V Leiden‘). This is less common, but makes the risk of venous thrombosis much higher - around eighty times the normal risk.

Prothrombin 20210

Prothrombin is a clotting factor, and people with the 20210 gene have a change in their prothrombin which makes the blood clot more easily. About 1 in 50 people of European origin have this gene; it is more common in people of South European origin. It increases your risk of a venous thrombosis to twice the normal risk. This is a relatively low risk, so most people with prothrombin 20210 do not get clots.

Protein C deficiency

Protein C is a natural anti-clotting chemical in the blood. The deficiency can be genetic, or due to other conditions such as kidney disease. With inherited protein C deficiency, the risk of blood clots varies between families, as each family has a different alteration in the protein C gene. The best guide to your level of risk is whether you or your relatives have had a venous thrombosis. If a child inherits two genes with protein C deficiency (one from each parent - this is very rare), they will have a more severe problem and will get blood clots in the skin soon after birth. This is treated with protein C concentrates and anticoagulant medication.

Protein S deficiency

Protein S is also a natural anti-clotting chemical in the blood. Protein S deficiency is rare. The risk of venous thrombosis varies between families, and the best guide to your risk is to look at whether other relatives have had a thrombosis.

Antithrombin deficiency

Antithrombin is another of the natural anti-clotting chemicals in the blood. There are different types of antithrombin deficiency, both genetic and due to other diseases. The inherited form is rare, affecting about 1 in 2,000 people.

Antithrombin deficiency is a fairly severe type of thrombophilia. The risk of a blood clot varies between families, but can be increased by 25-50 times the normal risk. With this condition, blood clots can occur not only in the legs or lung, but also in the veins of the arms, gut, brain or liver. About 1 in 2 people with antithrombin deficiency get a blood clot before the age of 30, but others may reach old age without problems.

With this condition, if you do develop a clot, you may be advised to take long term warfarin medication. However, this must be decided on an individual basis. Also, treatment with antithrombin concentrates can be given when there is a higher risk of clots, for example if you are having major surgery.

With pregnancy, anticoagulant treatment with heparin is usually needed. Treatment with antithrombin concentrates can also be used.

Children can have antithrombin deficiency - parents need to be aware so that they can detect signs of a blood clot. Although most children don’t get a clot, they are at risk of clots in situations such as surgery. Also, some newborn babies may get clots. Anticoagulant treatment or antithrombin concentrate may be needed. Parents who have antithrombin deficiency themselves and are expecting a child, should discuss this with their doctor.

Dysfibrinogenaemia

This is a rare genetic defect where fibrinogen (a clot dissolving chemical) is altered. There may be increased clotting, increased bleeding or both.

Combined inherited thrombophilias

Some people inherit more than one thrombophilia gene, for example, factor V Leiden plus prothrombin 20210. With combined thrombophilias, the risk of getting a clot is multiplied and there is a much greater risk than with either condition alone.

Acquired thrombophilias

Acquired thrombophilias are not inherited, and usually start in adulthood.

Antiphospholipid syndrome

This is called APS for short. It is caused by certain antibodies (immune system chemicals) in the blood, which are called antiphospholipid antibodies. APS causes clots in arteries and small blood vessels, as well as venous thrombosis. In particular, clots may occur in the brain, causing a stroke.

APS can affect pregnancy in some cases. Many women with APS do not have problems in pregnancy. However, APS may cause miscarriage, or other problems - growth restriction of the fetus, pre-eclampsia or rarely, fetal death. These problems can be reduced by treatment.

APS can be treated with low-dose aspirin, which is helpful in pregnancy. If you have had a blood clot, then warfarin is usually advised instead (or heparin if you are pregnant).

Other acquired conditions

Other medical conditions can increase the risk of blood clots: some doctors classify these as thrombophilias. Examples are: certain disorders affecting blood platelets, some bone marrow disorders, kidney or heart problems, inflammatory bowel disease and advanced cancer.

Mixed inherited/acquired thrombophilias

These are due to both genetic and non-genetic causes.

Hyperhomocysteinaemia

This is a raised level of a chemical called homocysteine in the blood, which is thought to increase the risk of blood clots in arteries and veins because it damages blood vessels. This is a relatively mild condition, but it can add to the 'risk factors' for clots. Vitamin B12 and folic acid may help.

Paroxysmal nocturnal haemoglobinuria

This is a rare condition affecting the bone marrow. It can lead to venous thrombosis, often in unusual sites such as the veins of the gut, liver or brain. Anticoagulation may be needed, and there are other treatments too for this condition.

Elevated factor VIII

This is pronounced "factor 8". It is due to abnormally high levels of factor VIII, which is one of the blood chemicals that promotes clotting. Depending on the actual level of factor VIII, it can increase the clotting risk by about six times - this is a relatively low risk for getting a clot.

Further help and information

Lifeblood

A charity dedicated to increasing awareness and prevention of thrombosis; provides detailed leaflets and information about many types of thrombophilia.
Tel: 020 7633 9937 Web: www.thrombosis-charity.org.uk

Protein S Deficiency and Thrombophilia

A patient website and forum with information about protein S deficiency.
Web: www.protein.org.uk