Introduction

Thrombophilia is a medical condition affecting the blood, in which a person becomes more susceptible to forming blood clots in their bodies.¹ These can occur in the arteries, causing problems such as heart attacks and strokes, as well as the veins, causing a group of conditions known as venous thromboembolism. Examples of venous thromboembolisms include pulmonary embolisms, in which a clot forms in a vein in the lungs causing respiratory symptoms, and deep vein thrombosis, in which a clot forms in the deep veins of a limb, causing pain due to loss of blood flow. 

Sometimes, thrombophilia is inherited from our parents through genetics. The condition Factor V Leiden is one example of this, and it is one of the most common causes of thrombophilia in the UK.² You may be tested for Factor V Leiden if you have experienced blood clots and you have a family history of blood clots. Despite this, thrombophilia is not always genetic, and it can be caused by many other factors. Sometimes it is permanent, and sometimes it is induced temporarily, for example by pregnancy or certain medications.^3,4 

This article aims to cover what causes thrombophilia, its complications and its treatment and management. 

Thrombophilia and blood clotting

Our body forms blood clots as a defence mechanism against bleeding. This occurs mainly for three reasons: injury to our blood vessels, if our blood sits still for a long time, or if we have a disorder that causes our blood to be prone to clotting (like in thrombophilia).⁵ Clots form from fragments of cells known as platelets, which form a plug-like structure at the vessel walls to prevent bleeding.⁵ Extra proteins in the blood, called clotting factors, also react in a complex way that helps strengthen this clot.⁶ 

Though clot formation is incredibly useful and necessary in our bodies, for example in preventing internal and external bleeding, clots forming too easily can lead to several problems as discussed throughout the rest of the article.

Causes of Thrombophilia

Thrombophilia has many causes, and these can be grouped into two categories: genetic causes and acquired causes. 

There are a number of genetic causes of thrombophilia, linked to one or more specific gene mutations that have been passed down from our parents. Examples of these genetic causes of thrombophilia include the following:¹ 

• Factor V Leiden
• Protein C deficiency
• Anti-thrombin deficiency
• Protein S deficiency
• Prothrombin gene mutation

These conditions make developing a blood clot more likely. Despite this, many people with a diagnosis of genetic thrombophilia may never have a blood clot form in their bodies.¹ Rather, patients with a diagnosis who also have other acquired risk factors for thrombophilia are the ones who tend to experience recurrent clots.

Acquired causes of thrombophilia include but are not limited to, the following:¹

• Antiphospholipid syndrome 
• Surgery and hospitalisation
• Immobility
• Drugs including the oral contraceptive pill 
• Hormone replacement therapy (HRT) in menopause
• Pregnancy
• Cancer
• Obesity
• Smoking
• Old age

Some of these risk factors are modifiable, meaning that you can avoid them. For example, you may be able to find a form of contraception that doesn’t increase clot risk, lose weight if you are obese, or stop smoking. Others on this list are non-modifiable, meaning that they cannot be changed, for example, old age. Being aware of what increases your risk of clotting is important, as you can look out for the signs if you recognise any symptoms. 

Symptoms and complications of thrombophilia

This section will briefly discuss some of the symptoms of thrombophilia, and what complications these may lead to if thrombophilia goes unrecognised for a long time.

One of the most common presentations of thrombophilia is deep vein thrombosis. Deep vein thrombosis (DVT) occurs when a clot forms in the deep veins of the body, normally in the legs but rarely in the arms. Typically, DVTs present with swelling, pain, warmth and redness of the affected limb.⁷ It is uncommon for DVTs to occur on both sides of the body, so if you are experiencing these symptoms in both legs or both arms, it may be more likely to be a different diagnosis. DVTs are diagnosed by clinicians using a clinical examination, an ultrasound of the affected limb and sometimes a blood test.⁷ They are treated using medication that helps prevent the formation of clots, and typically patients are on a course of this for 3-6 months before review by their doctor. 

Another presentation of thrombophilia is a pulmonary embolism. This is when a clot occurs in a vein in the lungs, causing symptoms including shortness of breath and pain during inspiration. ⁷ It tends to be diagnosed using a CT scan and a blood test. Treatment for pulmonary embolism is very similar to treatment of DVT, depending on the severity of the clot in the lungs and the patient’s symptoms.

Thrombophilia can also cause strokes known as ischaemic strokes. Ischaemic stroke occurs when a clot forms in one of the arteries of the brain, blocking off circulation and causing tissue to lose blood flow, causing a phenomenon known as ischaemia.⁸ Ischaemia can lead to tissue death in the brain, and therefore cause lifelong brain damage. Symptoms of stroke to watch out for include slurring of speech, weakness of the limbs or face (particularly on one side of the body) and visual changes or vision loss.⁸ Stroke can be diagnosed with a CT scan of the head. If you suspect someone you know is having a stroke, go to the emergency department or ring 999 immediately, as faster treatment often leads to better results. 

Lastly, clots that form sporadically can lead to heart attacks. They occur when the clot moves to the arteries that supply oxygen to the muscle walls of the heart, known as the coronary arteries.⁹ Signs of heart attacks include chest pain that may also be felt in the arms and the shoulder/neck/back, shortness of breath, nausea and vomiting. Heart attacks can be diagnosed using an electrocardiogram (ECG), which involves having sticky probes stuck to your chest to create an image of how your heart is beating. It is a straightforward, non-invasive test. Similarly to stroke, if someone you know is suspected to be having a heart attack, call for medical help as fast as possible. 

Considering these symptoms of thrombophilia, it is unsurprising that patients with a diagnosis often have long-term disabilities or chronic health conditions due to repeated clots. As stated earlier in the article, many patients with the genetic predisposition to thrombophilia do not ever experience a blood clot, however, being aware of the signs and symptoms of the conditions above is important in ensuring they can seek medical help if required. 

Diagnosis of Thrombophilia

Thrombophilia may be diagnosed in two ways: either through suspicious symptoms raising a patient’s concern, or through previous family history. If a doctor suspects a patient may have thrombophilia, they may do tests including the following:¹⁰

• Blood tests, specifically including a clotting screen to see how quickly blood clots form
• Genetic testing
• Specific testing for antiphospholipid antibodies, which are proteins that are present in the blood in antiphospholipid syndrome (one type of thrombophilia)

In addition, if a patient is presenting with symptoms of a clot such as a DVT or a stroke, the relevant scans will be done (for example a leg ultrasound or CT scan of the head).⁷ 

Alternatively, if a patient has strong known risk factors for thrombophilia such as pregnancy or a current cancer diagnosis, they may not be investigated as thrombophilia will be an assumed, temporary diagnosis.

Treatment and management

Treatment of thrombophilia is specific to each patient, based on what symptoms they are experiencing. If a patient has been diagnosed with a genetic cause of thrombophilia but has no  history of clots, they may not need medical intervention and instead may benefit from close monitoring.

Others will be started on blood thinner medications such as apixaban or warfarin, which makes the blood less likely to clot.¹⁰ The main side effect of this type of medication is that it makes you more prone to bleeding, so patients are advised to be cautious and to call for medical help if they injure themselves and are bleeding. 

Lifestyle changes play a big role in how thrombophilia is managed, and advice for patients either at risk of thrombophilia or with a diagnosis of thrombophilia should be educated on changes they can make to reduce their risk of clots. Some of these changes are listed below:¹⁰

• Healthy diet
• Regular exercise
• Weight loss, if a patient is overweight or obese
• Giving up smoking
• Avoiding long periods of sitting or lying still, or wearing compression socks/stockings if this is unavoidable 

Summary

Living with thrombophilia can present numerous challenges, but education on the signs to look out for clots and knowledge of strategies to prevent them can help ensure that patients with thrombophilia can enjoy a normal life and do all the activities that they would have before their diagnosis! For those struggling with their thrombophilia diagnosis, support is available at charities such as Thrombosis UK, and individuals are always encouraged to see their GP if they have any worries or questions about the future of living with thrombophilia.¹¹