What is Thrombophilia?

Thrombophilia causes problems with blood clotting. People with this condition have blood that clots too much and they also have problems with old clots sticking around too long. Though lots of people manage this condition very well, some end up needing emergency care.

The most common type of thrombophilia is Factor V Leiden thrombophilia. This is found in between 5% and 8% of people of European descent.

Many people don’t realise that they have the condition until they have another problem that reveals it. For example, just under 50% of people with a pulmonary embolism could have thrombophilia.

Overall, though, the true thrombophilia presence isn’t known. This is because of how complex it is and how many different types there are. It is believed that current data underestimates the prevalence.

For inherited thrombophilia, there are between 1% and 20% of the general population affected with Factor V Leiden thrombophilia. This figure goes up to between 18% and 50% when taking into account patients who have recurrent thrombosis.

What is thrombophilia?

As previously mentioned, thrombophilia is a blood-clotting disorder. It is sometimes called a prothrombotic state or hypercoagulability. This condition increases the risk of thrombosis (this is when you have blood clots in your blood vessels).

When people are identified as having a thrombosis episode such as deep vein thrombosis (DVT) in their legs, half of them will have thrombophilia. It is believed that many people have a thrombophilic abnormality, but most will only get thrombosis when they have one or more additional risk factors.

Thrombophilia is usually described as a genetic (inherited) or acquired tendency for developing thrombosis.

How does thrombophilia affect the body?

This condition can cause thrombosis because too much clotting protein is being made. These abnormal clotting proteins become resistant to breaking down and produce too few proteins that are needed for thrombosis prevention. They can also damage blood vessel walls. If you have thrombophilia, you can get thrombosis in your veins, arteries, or both.

All types of thrombophilia increase a person’s risk of having thrombosis for the first time. However, not all types of thrombophilia increase a person’s chances of recurrent thrombosis.

The most common thrombosis types caused by thrombophilia are pulmonary embolism and deep vein thrombosis. This is much more likely if anticoagulation isn’t prescribed. What’s more, the antiphospholipid antibodies produced increase a person’s risk of having a stroke or heart attack.

In women, there are greater consequences. Having thrombophilia increases a woman’s risk of developing thrombosis linked to birth control pills or hormone replacement therapy (HRT). For some women, thrombophilia can cause infertility or recurrent miscarriage. When women are pregnant, it can increase their risk of developing maternal thrombosis and other pregnancy complications.

What are the types of thrombophilia?

There are two categories of thrombophilia and then many types within those. Thrombophilia causes can be classified as acquired or inherited. Inherited thrombophilia is genetic and can be passed on between parents and their children.

Acquired thrombophilia isn’t inherited and has nothing to do with a person’s genes. Generally, acquired thrombophilia occurs in adulthood either due to medical problems developing or immune system problems.

It is also possible to have mixed thrombophilia that is caused partly by non-genetic factors and partly genetic factors.

Inherited thrombophilia

There are a few different types of inherited thrombophilia. We’ll discuss them in this section.

Factor V Leiden

This type of thrombophilia is quite common in Europeans. It is believed that around 1 person in every 20 has the Factor V Leiden gene. This gene affects the Leiden gene at Factor V, hence its name, and it makes the process of clotting go on for longer. This then increases a person’s risk of developing blood clots in their veins by around eight times. This is still quite a low risk and so most people who have the Factor V Leiden gene don’t have problems.

Some people will inherit two copies of the Factor V Leiden genes (one from each parent). This is known as ‘homozygous Factor V Leiden’. This is not as common, but the risk is much higher with this – around 80x the usual risk.

Prothrombin 20210

Prothrombin is associated with clotting. People with the Prothrombin 20210 gene have different prothrombin, which means the blood clots very easily. One person in every fifty has this gene in Europeans in general, but it is more prevalent in southern Europeans.

With Prothrombin 20210, you have a risk of developing blood clots in your veins that is twice that of a normal person. This is still classed as low risk and so most people with the Prothrombin 20210 gene won’t develop blood clots.

Protein C deficiency

This is a natural anticoagulant that is in our blood. People can be deficient genetically or because of a condition like kidney disease. When the deficiency is inherited, the blood clot risk varies among families, depending on the specific gene alteration. If two protein C deficiency genes are inherited, the thrombophilia will be worse – though this is rare.

Protein S deficiency

Like protein C, protein S is a blood anticoagulant and you can be deficient in it either due to inheriting a gene or from an illness.

Antithrombin deficiency

Like protein C and protein S, antithrombin is another anticoagulant. You can be deficient in this either genetically (though this only affects 1 in every 2,000 people) or due to other conditions.

When you have an antithrombin deficiency, your thrombophilia is pretty severe. The risk of blood clots increases by 25 to 50 times. What’s more, antithrombin deficiency causes blood clots in the liver, brain, gut and arms as well as the lungs and legs.

Around 50% of people with antithrombin deficiency end up developing a blood clot before they reach the age of 30.

Many people with antithrombin deficiency take a drug called warfarin. During pregnancy, heparin is given instead of warfarin.

Dysfibrinogenaemia

This is a rare form of thrombophilia that is caused by a genetic defect. This occurs when fibrinogen doesn’t work properly. This is a chemical that dissolves clots and so, as a result, there can be increased bleeding or clotting.

Combined-inherited thrombophilia

It is possible to inherit more than one gene that causes thrombophilia, e.g., Prothrombin 20210 in addition to Factor V Leiden.

When you have combined thrombophilia, the risk is much greater.

Acquired thrombophilia

This condition also has many types and is not inherited. It usually starts during adulthood.

APS – antiphospholipid syndrome (Hughes’ syndrome)

This syndrome is caused by antibodies named antiphospholipid antibodies. It can cause blood clots in veins, arteries and smaller blood vessels. It can also affect pregnancy for some women as it can cause miscarriage, growth restriction and pre-eclampsia. Rarely, it can also cause foetal death.

This condition can be treated with aspirin (a low dose) and if a blood clot develops, warfarin or heparin (for pregnant women) is given.

Other conditions

There are some other conditions that medics class as thrombophilia. These include disorders of the bone marrow or platelets, kidney problems, advanced cancer and inflammatory bowel disease (IBD).

What causes thrombophilia?

Thrombophilia alters the body’s natural blood-clotting process, which is called haemostasis. When functioning well, this process stops you from bleeding when you cut yourself or have another injury.

When blood vessels are injured, haemostasis is triggered. A series of reactions occur called the clotting cascade where chemicals (clotting factors) in the blood respond. This clotting cascade means blood solidifies into clots, which then stick to the injury. Platelets (small particles in the blood) also help the clot to form.

The blood also contains other chemicals that act against this clotting mechanism to prevent too much blood clotting.

In thrombophilia, the normal balance of chemicals in the blood is disturbed. You could have too much of a clotting factor chemical, for example, or too little of the chemical that opposes blood clotting. The name for unwanted blood clots is thromboses.

What are the risk factors of thrombophilia?

When people have thrombophilia, it means they are more likely to develop blood clots compared to healthy individuals.

The most common risk factors for this condition are:

• Immobilisation.
• Advanced age.
• Pregnancy.
• Inflammation.
• Using oral contraceptives.
• Diabetes mellitus.
• Obesity.
• HRT (hormone replacement therapy).
• Antiphospholipid syndrome.
• Cancer.

Though these aren’t thrombophilia causes, they are associated with an increased risk. Due to a high prevalence of diabetes and cancer as well as an ageing population, thrombosis is likely to affect more and more people in the near future.

What are the signs and symptoms of thrombophilia?

Thrombophilia symptoms encompass different parts of the body, depending on where a blood clot has formed.

Here are some common thrombophilia symptoms.

• Brain – Sudden headache, seizures, difficulty seeing or talking, weakness on one side of the body.
• Heart – Chest pain, shortness of breath, painful left arm, feeling light-headed, sweating, nausea.
• Lung – Faster heart rate, fast breathing, painful deep breathing, shortness of breath, chest pain.
• Abdomen – Vomiting, nausea, pain.
• Arm or leg – Warm feeling, pain, swelling.

How common is thrombophilia?

As previously mentioned, it is difficult to know how many people have thrombophilia as it often only makes itself present when a blood clot forms. There are people who could have thrombophilia who never actually have a blood clot.

Major thrombophilias are rare. Antithrombin deficiency affects around 0.2% of the population (and between 0.5% and 7.5% of people who have venous thrombosis). Similarly, protein C deficiency is thought to be present in 0.2% (and between 2.5% and 6% of people who have thrombosis). For protein S deficiency, you’re looking at between 1.3% and 5% of people who have thrombosis (the wider prevalence in the general population isn’t known).

Factor V Leiden occurs in around 5% of people who have North European heritage. It is rare in people of African and Asian extraction. In people who have thrombosis, one in ten have Factor V Leiden.

How is thrombophilia diagnosed and treated?

When thrombophilia is suspected (either due to thrombosis or another reason), there are tests that can be carried out to determine the diagnosis.

These include:

• A full blood count (FBC) – With an examination of the blood on film.
• Prothrombin time (PT) – To evaluate the blood’s coagulation pathway.
• Partial thromboplastin time (PTT) – A blood test to characterise the blood’s coagulation.
• Thrombodynamics test.
• Thrombin time TT – Measuring the time it takes for a clot to form.
• Reptilase time (RT) – A blood test that looks for abnormalities or deficiencies in fibrinogen.
• Genetic testing to look for Factor V Leiden or prothrombin mutation.

To diagnose the condition as a hereditary case, the patient needs to have a family history plus two abnormal tests.

Treatment

There is no one specific thrombophilia treatment. When people have recurrent or unprovoked thrombosis (or are at a higher risk of thrombosis), they may be prescribed anticoagulation medications like warfarin as an ongoing treatment and preventative measure. A medication manager will help to decide what treatment is best.

The risk of thrombosis needs to be weighed against the risks of taking a medication like warfarin, which can cause significant bleeding.

Women who have thrombophilia who are contemplating pregnancy (or who are already pregnant) will usually be prescribed a different medication like heparin. This is because warfarin can cause abnormalities in babies, especially in the first trimester.

Final thoughts on thrombophilia

Sometimes called a prothrombotic state or hypercoagulability, thrombophilia is an abnormality in the blood’s ability to clot. This increases the thrombosis risk. When people have been identified as having a thrombosis episode (like deep vein thrombosis, or DVT), half of them will have thrombophilia. There is a significant number of people who have thrombophilic abnormalities but most people will only develop thrombosis when they have other risk factors like advanced cancer or obesity.

In terms of treatment, there is no one-stop shop. If people suffer from recurrent thromboses, they might end up needing long-term anticoagulation treatment like warfarin or heparin as a preventative measure.

Finally, there is still so much more to learn about this condition. If we consider the fact that the first major form of this wasn’t identified until the mid-1960s with the others following later in the 1990s, what we know about this disease is very small.