Imagine your body’s defence mechanism turning against you, attacking not just the nasty microbes but also your own tissue and organs. This is the case for people with autoimmune conditions. This can lead to thrombosis, which involves the formation of blood clots within your blood vessels. Syndrome (APS) is one of the main examples of autoimmunity, which can result in abnormal clotting seen in thrombosis. 

The connection between autoimmune disorders such as APS and thrombosis is very important to understand, as it can lead to detrimental consequences. It is important to understand more about these events and their underlying conditions to prevent future potential blood clots from forming, to improve the quality of life for those affected.

Understanding thrombosis

Blood clots are helpful, for example, when you cut your finger, the clotting is what stops excessive bleeding. However, when blood clots form inside your blood vessels in an uncontrolled manner, they can block your blood flow, which is very dangerous. This is thrombosis, and it affects 1-2 per 1000 people every year.¹

There are two types of thrombosis:

• Venous thrombosis occurs within the veins, which carry blood back to the heart. The most common type is deep vein thrombosis (DVT), and this usually occurs within the legs. The blood clots can break, and fragments/debris can travel within the bloodstream and reach the lungs, which can cause pulmonary embolism, which is fatal.² Symptoms of DVT include pain, swelling, redness and warmth within the affected limb³
• Arterial thrombosis: it forms within the arteries, which deliver oxygen from the heart to the rest of the body. These clots can result in strokes if they block the flow of blood to the brain or myocardial infarction (heart attacks) if they block the coronary arteries, which supply oxygenated blood to your heart. Symptoms for this occur very fast, including facial drooping  (seen with strokes) and shortness of breath or chest pain, commonly seen with heart attacks

There are various risk factors for thrombosis, such as genetics or age; these are non-modifiable risk factors. However, ones that we can control (modifiable risk factors) are smoking, obesity, sedentary lifestyle, and birth control pills.⁴ Medical conditions, such as cancer, certain inflammatory bowel diseases, such as Crohn's disease, lung disease, and heart disease, can cause thrombosis.⁴

Autoimmune disorders and their role in thrombosis

Our immune system works as an effective security force for unwanted microorganisms that enter our body, whilst leaving our harmless cells alone. However, people with autoimmune conditions have a faulty security system. Their body attacks its own body cells because their immune system produces antibodies (also called autoantibodies) that target the body’s own cells and tissues. This leads to inflammation and tissue damage. 

This can occur via different mechanisms:

• Chronic inflammation: When there is damage to the endothelium (a thin layer of cells that line blood vessels), this activates platelets and the clotting cascade, which leads to the formation of a thrombus (blood clot)²
• Autoantibodies: these directly interfere with the clotting cascade, some target clotting factors or platelets, whilst others target phospholipids  (fat molecules)important for normal cell function

There are various autoimmune conditions that have this relationship with thrombosis:

• Rheumatoid arthritis⁵
• Inflammatory bowel disease⁶
• Systemic lupus erythematosus (SLE)⁷
• APS⁸

Anti-phospholipid syndrome (APS): A closer look

APS involves the collision of both autoimmunity and clotting abnormalities. Although it affects many people, it is often underdiagnosed.

It involves the formation of antiphospholipid antibodies (aPLs) that target and attack phospholipids and phospholipid-binding proteins. Symptoms include:⁹

• Stroke
• Blood clots within the legs - DVT
• Rashes
• Transient ischemic attack
• Repeated miscarriages or stillbirths
• Cardiovascular diseases
• Neurological symptoms such as migraines, dementia, chronic headaches, etc.
• Low platelet count (thrombocytopenia)

Diagnosis and laboratory testing

The main tests within the laboratory to diagnose APS include the detection of these antibodies: 

• Lupus anticoagulant (LA)
• Anticardiolipin antibodies (aCL): target cardiolipin- a phospholipid found within cell membranes¹⁰
• Beta 2 glycoprotein 1 antibodies (b2GP1)

Repeated positive tests ensure that misdiagnosis cannot occur from temporary antibody elevations during infections or inflammation. False positives occur in cases of certain infections, such as HIV or certain medications. But it is worth keeping in mind that antibody levels can also fluctuate, and at times, it may be undetectable. This is why doing repeated tests is important in diagnosing. 

Management and treatment approaches

Treating APS requires a careful approach to prevent any excessive bleeding from occurring. Treatment plans are typically centred around anticoagulation therapy but need to be personalised according to patient history, risk factors and antibody levels.

Common treatments include:¹¹ 

• Anticoagulants such as heparin break up clots
• Antiplatelet drugs: clopidogrel
• Low-dose aspirin prevents clots in your arteries
• Warfarin thins your blood to prevent blood from clotting

If you are pregnant, you are more likely to be prescribed:

• Enoxaparin
• Intravenous immunoglobulin (IVIG) reduces the risk of worsening the illness that you have
• Corticosteroids: reduce inflammation and suppress your immune system

Lifestyle changes you can make:

• Stop smoking, as components of cigarettes increase the risk of clotting
• Increase physical activity, which will improve your vascular health
• Maintain a healthy weight, which will decrease the overall risk
• Avoid sedentary lifestyles, for example, sitting for long durations

Conclusion

The connection between autoimmune conditions and thrombosis is an important link to understand. APS showcases how an uncontrolled immune system can create perfect conditions for the formation of blood clots and thus leading to thrombosis.

For doctors, understanding this is important as it will make it easier to diagnose APS, preventing any potential consequences.  Young patients with unexplained blood clots, people with unusual clots in random places, and women with stillbirths or repeated miscarriages should be checked for underlying autoimmune conditions, especially APS. 

For patients, however, learning and understanding this will enable people to take an active approach to changing their lifestyle to decrease the risk of autoimmune conditions and thrombosis.

FAQs

If I have an autoimmune disorder, should I be worried about blood clots?

The risk depends on the condition you have. While APS has a high risk, conditions such as IBD and rheumatoid have moderate risks.  Make sure to talk to a healthcare professional about your personal risks and the preventative steps that you can take.

Can APS be cured?

Right now, there is no cure for APS. With the right treatment, however, most patients can control their condition well. 

Can stress cause clotting problems in people with autoimmune disorders?

Stress can increase inflammation levels and make your condition worse. Therefore, stress management activities such as meditation. Regular exercise and getting enough sleep is important in preventing the worsening of your autoimmune condition.

How does APS affect pregnancy? Can I have children?

Although APS increases the risk of miscarriages and stillbirths, with special care and monitoring, it is estimated an 80% of pregnancies will a successful.⁸

Will my children be at risk if I have APS or another autoimmune disorder?

Although APS and other autoimmune conditions are not passed down like other conditions, having a family member with antiphospholipid antibodies increases the chance of the children also developing them.

What signs or symptoms show that my blood clot is related to an autoimmune condition?

If you have a blood clot without any obvious cause, such as surgery, or the clots are in unusual places, it will most of the time point to an autoimmune condition. Young people with myocardial infarction or strokes, or women with miscarriages, should be checked for autoimmune conditions immediately, as it can be a sign of APS.