What is antiphospholipid syndrome?
Antiphospholipid syndrome (APS), also known as Hughes syndrome, is a disorder of the immune system that causes an increased risk of blood clots and miscarriages.
People with APS are at risk of developing conditions such as deep vein thrombosis (a blood clot that usually develops in the leg) and arterial thrombosis (a clot in an artery), which can cause a stroke or heart attack.
Pregnant women with the syndrome have an increased risk of having a miscarriage, although the exact reasons for this are uncertain.
APS can affect people of all ages, including children and babies. However, it usually affects adults aged 18–40, and affects five times as many women as men.
There is currently no cure for APS. However, if it is correctly diagnosed, the risk of developing blood clots can be greatly reduced.
It is possible for APS to be misdiagnosed because its symptoms can be similar to those of multiple sclerosis (a common condition that affects the central nervous system). Symptoms of both conditions include:
- balance and mobility problems
- vision problems, such as double vision
- speech and memory problems
- a tingling sensation or pins and needles in your arms or legs
- fatigue (extreme tiredness)
However, symptoms indicating that a person has APS rather than multiple sclerosis include:
- repeated headaches or migraines
- a previous history of blood clots
- repeated miscarriages
Read more about the symptoms of APS.
Blood tests designed to help identify the antibodies (proteins) responsible for APS are essential in diagnosing the syndrome. Three main types of antibodies can be measured:
- anti-B2 doctorI
- the lupus anticoagulant
Read more about how APS is diagnosed.
What causes APS?
APS is an autoimmune condition. This means the immune system, which usually protects the body from infection and illness, attacks healthy tissue.
The immune system produces abnormal antibodies called antiphospholipid antibodies. They bind to proteins and fats in the blood, including an important type of fat called phospholipid.
Phospholipids and proteins are thought to help keep the blood at the right consistency. If the fats and proteins are bound by antibodies, the blood becomes more likely to clot.
It is not known what causes the immune system to produce abnormal antibodies, but like other autoimmune conditions, both genetic and environmental factors are thought to play a part.
Read more about the causes of APS.
As there is no cure for APS, treatment aims to reduce the risk of developing further blood clots.
Anticoagulant medicines, such as warfarin, or an antiplatelet, such as aspirin, are usually prescribed. These reduce the likelihood of blood clots forming when they are not needed but still allow clots to form when you cut yourself.
Additional treatment is also available for pregnant women with APS to help improve their chances of having a successful pregnancy.
Read more about how APS is treated.
Despite serious and potentially life-threatening consequences, most people respond well to anticoagulants and can lead normal, healthy lives. Treatment can also help improve the outcomes of pregnancy in 75–80% of women.
Despite having serious and potentially life-threatening consequences, most people respond well to anticoagulants and the outlook is generally good.
Treatment with anticoagulants can also help improve the outcomes of pregnancy and an estimated 75-80% of women will have a successful pregnancy after being treated.
A small number of people with APS continue to experience blood clots despite having extensive treatment.
In antiphospholipid syndrome (APS), the immune system produces abnormal antibodies which make the blood stickier than normal.
This means that a person with APS is more likely to form blood clots in their veins and arteries. This can cause serious, life-threatening health problems, such as deep vein thrombosis (DVT), strokes or heart attacks (see below).
Below are the most common conditions that are caused by APS. It is important to note that most people with APS will not experience all of them.
Deep vein thrombosis
Deep vein thrombosis (DVT) is one of the most common conditions that can occur as a result of APS. It is a blood clot that develops inside one of the body's larger, deeper veins, usually inside the calf or thigh.
Symptoms of DVT include:
- pain, swelling and tenderness in one of your legs (usually only one leg is affected)
- a heavy ache in the affected area
- warm skin in the area of the clot
- redness, particularly at the back of your leg, below the knee
One of the biggest risks is that the blood clot may move out of your leg and travel towards your lungs. A blood clot that reaches the lungs is known as a pulmonary embolism (see below)
Strokes and TIAs
A stroke is a serious condition that is associated with APS. A stroke happens when a blood clot blocks the brain's blood supply.
The most effective way of identifying the symptoms of a stroke is to remember the word FAST, which stands for:
- Face – the face may have fallen on one side, the person may not be able to smile, or their mouth or eye may have drooped.
- Arms – the person may not be able to raise both arms and keep them there due to weakness or numbness.
- Speech – their speech may be slurred.
- Time – request an ambulance immediately if there are any of these signs or symptoms.
A transient ischaemic attack (TIA), also known as a "mini-stroke", happens when a blood clot causes a temporary blockage of blood to the brain.
TIA symptoms are the same as those of a stroke, but they only last from a few minutes to a few hours before they disappear. However, a TIA should never be ignored because it is a serious warning sign of a problem with the brain's blood supply.
A heart attack can occur when a blood clot forms in one of your coronary arteries (the blood vessels that lead to the heart).
If the blood clot blocks the blood supply to your heart, it can seriously damage the heart muscles, which can die if left untreated.
Common symptoms of a heart attack are:
- a crushing pain or mild discomfort in the centre of the chest
- shortness of breath
- clammy, sweaty and grey complexion
- nausea and vomiting
- a general feeling of being unwell
Request an ambulance immediately if you think that you or someone else is having a heart attack.
A heart attack requires immediate emergency treatment so do not wait to get medical assistance.
A pulmonary embolism is a blockage in one of the blood vessels in the lungs. Most pulmonary embolisms occur when a blood clot that starts in one of the legs travels up into the lungs. Symptoms of a pulmonary embolism include:
- shortness of breath
- severe chest pain
- a persistent cough that may bring up blood-stained phlegm
If it is not treated, a pulmonary embolism can be life-threatening, so contact your doctor immediately if you suspect that you have one. If this is not possible, contact your local out-of-hours service.
Women with APS have a much higher risk of developing complications during pregnancy, particularly if it is not treated. Possible complications include:
- recurrent (three or more) early miscarriages, usually during the first 10 weeks of pregnancy
- one or more later miscarriages, usually after week 10 of pregnancy
- premature birth, usually at or before week 34 of pregnancy, which is often caused by pre-eclampsia (where a pregnant woman suddenly experiences an increase in blood pressure)
Livedo reticularis is a skin condition caused by small blood clots that develop inside the blood vessels of the skin.
It causes the skin to take on a blotchy red or blue appearance. Some people also develop ulcers (sores) and nodules (bumps).
Livedo reticularis is often more severe in cold weather.
Superficial thrombophlebitis is inflammation of the veins just under your skin, usually in your leg. The symptoms are similar to DVT but they are not usually as severe.
The symptoms of superficial thrombophlebitis include swelling, redness and tenderness along the affected vein and a high temperature of 38C (100.4F) or above (although this is less common). The symptoms usually resolve within two to six weeks.
Causes of antiphospholipid syndrome
Antiphospholipid syndrome (APS) is caused by the body’s immune system producing abnormal antiphospholipid antibodies.
This increases the risk of blood clots](yourmd:/condition/embolism) developing in the blood vessels, which can lead to serious health problems, such as [deep vein thrombosis (DVT), strokes or heart attacks.
However, many people have antiphospholipid antibodies and do not develop blood clots. It is not known why some women with these antibodies develop clots before having a miscarriage, while others do not (see below).
Antibodies are proteins produced by the immune system to help fight off infection and illness. Antibodies identify threats, such as bacteria and viruses, and signal to the immune system to release chemicals to kill them and prevent infection spreading.
In APS, the immune system produces abnormal antiphospholipid antibodies which, rather than attacking bacteria and viruses, mistakenly attack some of the fats and proteins in your blood, causing it to clot.
It is not known why the antiphospholipid antibodies attack fats and proteins, which then causes the blood to clot. However, most experts believe that keeping your blood at the correct consistency (not too runny and not too sticky) is a delicate balancing act that relies on different types of proteins and fats working together.
It is thought that when the antiphospholipid antibodies attack the fats and proteins, they disrupt the balance of the blood, making it stickier and increasing the risk of blood clots developing.
It is still not clear what causes the immune system to produce abnormal antibodies and why most people with abnormal antibodies do not experience symptoms. A combination of genetic and environmental reasons is thought to be behind it.
Research into the genetics around APS is still at an early stage, but it seems that the genes you inherit from your parents may play a role in the development of abnormal antiphospholipid antibodies.
APS is not passed down directly from parents to children in the same way that other conditions are (such as haemophilia and sickle cell anaemia), but having a family member with antiphospholipid antibodies does increase the chance of your immune system also producing them.
A study that was carried out in 2008 found that almost half of people with APS had a similar mutated gene, known as the STAT4 gene.
This gene is also thought to play a role in other autoimmune conditions, such as lupus, a complex condition that affects many parts of the body and causes a wide range of symptoms, and rheumatoid arthritis, which causes joint pain and stiffness.
This may explain why some people develop APS alongside another autoimmune condition.
It is thought that one or more environmental triggers may be needed to trigger APS in some people.
Environmental factors that may be responsible include:
- viral infections, such as the cytomegalovirus (CMV) or parvovirus B19
- bacterial infections, such as E. coli (bacteria often associated with food poisoning) or leptospirosis (an infection that is usually spread by certain animals and causes flu-like symptoms)
- certain medications, such as anti-epileptic medicine or the oral contraceptive pill
Another theory is that many people with abnormal antiphospholipid antibodies only go on to develop APS if they have a higher risk of developing blood clots, for example if they:
- eat a high cholesterol diet
- do not do enough exercise
- take the combined contraceptive pill
- take hormone replacement therapy (HRT)
- are obese
However, this does not explain why some children who do not have any of these risk factors develop APS.
Diagnosing antiphospholipid syndrome
As antiphospholipid syndrome (APS) shares similar symptoms with multiple sclerosis, diagnosing it can sometimes be tricky.
However, it is very important that an accurate diagnosis is made because the blood clots that occur as a result of APS can have serious consequences.
Specific blood tests
To diagnose APS, the blood needs to be tested for the abnormal antiphospholipid antibodies that increase the risk of blood clots.
The blood tests used are designed to test for APS and the condition cannot be detected using routine blood tests. Two blood tests are required with a six- to eight-week gap in between them.
Sometimes, harmless antiphospholipid antibodies can develop in the body for short periods of time, often as a result of an infection or as a side effect of medication, such as antibiotics.
Therefore, if antiphospholipid antibodies are identified during the first blood test, another test will be needed at a later date.
After the results of the blood tests have been confirmed, your medical history will be carefully assessed to check whether you have experienced any previous symptoms that may be caused by APS.
A diagnosis of APS can usually be confirmed if you have had:
- one or more confirmed blood clots
- one or more unexplained late-term miscarriages, at or after week 10 of your pregnancy
- one or more premature births, at or before week 34 of your pregnancy
- three or more unexplained early miscarriages, before week 10 of your pregnancy
Antiphospholipid syndrome treatment
There is no cure for antiphospholipid syndrome (APS), so treatment aims to reduce your risk of developing more blood clots.
These work by interrupting the process of blood clot formation. This means that blood clots are less likely to form when they are not needed, but they will still form when they are needed, for example when you cut yourself.
If aspirin and warfarin don't work, you may be prescribed a higher dose of warfarin or an additional anticoagulant called heparin.
Aspirin and warfarin are taken in tablet form and heparin is usually given as an injection. You can be trained to give the injections yourself.
Most people with APS will need to take anticoagulants for the rest of their life. A risk associated with this type of medication is that it can sometimes disrupt the blood’s ability to clot which can cause excessive bleeding (haemorrhage).
Symptoms of excessive bleeding include:
- blood in your urine or faeces
- black faeces
- severe bruising
- prolonged nosebleeds (lasting longer than 10 minutes)
- blood in your vomit
- coughing up blood
Contact your doctor immediately if you have any of these symptoms while taking an anticoagulant. If this is not possible, call your local out-of-hours service.
Women who are diagnosed with APS are strongly advised to plan for any future pregnancy. This is because treatment to improve the outcome of a pregnancy is most effective when it begins as soon as possible after an attempt to conceive.
If you do not plan your pregnancy, it may take several weeks before you realise that you are pregnant. There is a small risk that treatment to safeguard the pregnancy may fail.
Treatment during pregnancy involves taking daily doses of aspirin or heparin, or a combination of both, depending on whether you have a history of blood clots and previous complications during pregnancy. Warfarin is not recommended during pregnancy because it carries a small risk of causing birth defects.
After you have reached the last three months of your pregnancy, and the health of your baby has been confirmed, you may no longer need to take heparin. However, you may need to continue taking aspirin.
Complications of antiphospholipid syndrome
Catastrophic antiphospholipid syndrome (CAPS) is a rare but very serious complication of antiphospholipid syndrome (APS). It occurs in less than 1% of people with APS.
In people who develop CAPS, blood clots suddenly form throughout the body, resulting in multiple organ failure.
It is not clear what causes this but one case in five occurs after an infection, trauma or surgery.
The initial symptoms can be wide-ranging, depending on which organs are involved. Initial symptoms may include:
- swollen ankles, feet or hands
- increasing breathlessness
- abdominal pain
- blood in your urine (haematuria)
- mental confusion
- seizures (fits)
- coma (a state of unconsciousness where a person is unresponsive and cannot be woken up)
The symptoms usually develop suddenly and rapidly get worse.
Immediate admission to an intensive care unit (ICU) is required so that the body’s functions can be supported while the blood clots are treated with injections of high-dose anticoagulants.
Dial for an ambulance immediately if you or someone you know has APS which suddenly gets worse.
Even with the best available treatment, the outlook for catastrophic APS is poor, with an estimated 50% of people dying as a result of the condition.