Antiphospholipid syndrome (APS)
Antiphospholipid syndrome (APS), also known by some as Hughes syndrome, is a disorder of the immune system that causes an increased risk of blood clots.
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 APS also have an increased risk of having amiscarriage, although the exact reasons for this are uncertain.
It is estimated that APS is responsible for one in every six cases of deep vein thrombosis (DVT), strokes and heart attacks in people under 50 and one in every six cases of recurrent (three or more) miscarriages.
There is currently no cure for APS. However, if it is correctly diagnosed, the risk of developing blood clots can be greatly reduced.
What causes antiphospholipid syndrome?
APS is an autoimmune condition. This means the immune system, which usually protects the body from infection and illness, attacks healthy tissue by mistake.
In APS, the immune system produces abnormal antibodies called antiphospholipid antibodies that target proteins attached to fat molecules called phospholipids, which makes the blood more likely to clot.
It is not known what causes the immune system to produce abnormal antibodies, but like other autoimmune conditions, genetic, hormonal and environmental factors are thought to play a part.
Who is affected
APS can affect people of all ages, including children and babies. However, it usually affects adults aged 20–50, and affects three to five times as many women as men.
It's not clear how many people in the UK have the condition.
Signs and symptoms
As well having a history of conditions caused by blood clots, such as stokes and deep vein thrombosis, people with APS may have:
balance and mobility problems
vision problems, such as double vision
speech and memory problems
a tingling sensation or pins and needles in the arms or legs
fatigue (extreme tiredness)
repeated headaches or migraines
Diagnosing APS can sometimes be tricky, as some of the symptoms are similar to multiple sclerosis (a common condition affecting the central nervous system). Therefore, blood tests designed to help identify the antibodies responsible for APS are essential in diagnosing the condition.
How antiphospholipid syndrome is treated
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 aslow-dose 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.
Treatment with these medications can also help pregnant women improve their chances of having a successful pregnancy. With treatment, it's estimated there is about an 80% chance of having a successful pregnancy.
Most people respond well to treatment and can lead normal, healthy lives. However, a small number of people with APS continue to experience blood clots despite extensive treatment.
APS is an immune system disorder that causes an increased risk of blood clots
Symptoms of antiphospholipid syndrome (APS)
In antiphospholipid syndrome (APS), the immune system produces abnormal antibodies which make the blood stickier than normal.
This doesn't always cause any noticeable problems, but some people with APS have general symptoms that can be similar to those ofmultiple sclerosis (a common condition affecting the central nervous system). These 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)
People with APS may also experience repeated headaches ormigraines.
They are more likely to develop 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.
Below are the most common conditions that can be caused by APS. However, most people with APS will not experience all of these.
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 in the calf or thigh.
Symptoms of DVT can 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.
A pulmonary embolism is a blockage in one of the blood vessels in the lungs. Most pulmonary embolisms occur when a blood clot that develops in one of the legs travels up into the lungs. Symptoms of a pulmonary embolism can include:
a sharp, stabbing chest or upper back pain that may be worse when breathing in
shortness of breath
a cough, which is usually dry, but may include coughing up bloodor mucus containing blood
feeling light-headed or dizzy
A pulmonary embolism can be life-threatening if not treated, so you should seek immediate medical help if you have the symptoms above.
Strokes and TIAs
A stroke is a serious condition that is sometimes 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 dropped.
Arms – the person may not be able to raise both arms and keep them there due to weakness or numbness.
Speech – speech may be slurred or garbled, or the person may not be able to talk at all despite appearing to be awake.
Time – it's time to dial 999 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. You should dial 999 for an ambulance immediately if you think you or someone else has had a TIA.
A heart attack can occur when a blood clot forms in one of the blood vessels leading to the heart (coronary arteries).
If the blood clot blocks the blood supply to your heart, it can seriously damage the heart muscles, which can die if left untreated.
Symptoms of a heart attack can include:
chest pain, which is usually located in the centre of your chest and can feel like a sensation of pressure, tightness or squeezing
pain in other parts of the body, as if the pain is travelling outwards from your chest
shortness of breath
feeling or being sick
an overwhelming sense of anxiety (similar to having a panic attack)
Dial 999 immediately if you think that you or someone else is having a heart attack.
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 may be caused by pre-eclampsia (where a woman develops high blood pressure during pregnancy)
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). These symptoms are 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 38°C (100.4°F) or above (although this is less common). The symptoms usually resolve within two to six weeks.
Causes of antiphospholipid syndrome (APS)
Antiphospholipid syndrome (APS) is caused by the body’s immune system producing abnormal antibodies calledantiphospholipid antibodies.
This increases the risk of blood clots 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 people with these antibodies develop clots and others don't.
Antibodies are proteins produced by the immune system to help fight off infection and illness. Antibodies are part of the body’s defence system produced to help protect against ‘invading forces’, such as bacteria and viruses. Antibodies can signal to the immune system to release chemicals to kill them and prevent infection spreading.
In APS, the immune system produces abnormal antibodies which, rather than attacking bacteria and viruses, mistakenly attack proteins found on the outside of cells in the blood and in the walls of blood vessels.
These abnormal antibodies are called antiphospholipid antibodies because they were originally thought to target fat molecules known as phospholipids. However, it's now thought that their real target is proteins attached to these fat molecules.
It is not known how the targeting of these proteins causes the blood to clot more easily. 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, and this balance may be disrupted by the abnormal antibodies in people with APS.
It is still not clear what causes the immune system to produce these abnormal antibodies or why most people with abnormal antibodies do not experience symptoms, although a combination of genetic and environmental factors is thought to be responsible.
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.
Studies have shown that some cases of APS may be related to 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).
This may explain why some people develop APS alongside another immune system 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 (a bacteria often associated with food poisoning) or leptospirosis (an infection usually spread by certain animals)
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 an unhealthy diet that leads to high cholesterol levels in the blood
do not do enough exercise
take the contraceptive pill or hormone replacement therapy (HRT)
However, this does not explain why some children and adults who do not have any of these risk factors still develop APS.
Diagnosing antiphospholipid syndrome (APS)
It is very important that an accurate diagnosis of antiphospholipid syndrome (APS) is made because the blood clots that occur as a result of APS can have serious consequences.
Diagnosis depends upon obtaining a good medical history and doing relevant blood tests.
You will usually be referred to a haematologist (specialist in conditions affecting the blood) or a rheumatologist (specialist in conditions affecting the immune system) for tests and any necessary treatment if APS is suspected.
Specific blood tests
To diagnose APS, the blood needs to be tested for the abnormal antiphospholipid antibodies that increase the risk of blood clots. APS cannot be detected during routine blood tests, so tests specifically designed for look for these antibodies need to be carried out.
The three main types of antibodies that can be measured during these blood tests are called:
anti-beta2 glycoprotein I
Two abnormal blood test results with at least a 12-week gap between them are required for APS to be diagnosed. This is because harmless antiphospholipid antibodies can sometimes 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.
If antiphospholipid antibodies are identified during the first blood test, another test will be needed at a later date to confirm whether the abnormal antibodies are still present.
If blood tests confirm that you have APS, 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 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
Treating antiphospholipid syndrome (APS)
There is no cure for antiphospholipid syndrome (APS), so treatment aims to reduce your risk of developing more blood clots.
As part of your treatment, you will be prescribed anticoagulant medicines such as warfarin or an antiplatelet medication such as low-dose aspirin.
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.
Your treatment plan
Most people with APS will need to take anticoagulant or antiplatelet medication daily for the rest of their life.
If blood tests show that you have abnormal antiphospholipid antibodies but you do not have a history of blood clots, low-dose aspirin tablets are usually the first treatment recommended. If you cannot take aspirin, you may be prescribed an alternative antiplatelet tablet called clopidogrel.
Warfarin tablets are usually recommended if you have APS and a history of blood clots, such as previously having deep vein thrombosis (DVT) or a stroke. However, this will need to be changed if you become pregnant or are planning a pregnancy (see below), so you should tell your doctor if this is the case.
If you develop a blood clot or your symptoms suddenly become severe, injections of an anticoagulant called heparin may be needed. These injections may be given in hospital, or you may be trained to give them yourself.
Side effects of these medications are uncommon and generally mild, such as indigestion or feeling sick (nausea).
However, there is a risk that the disruption to the blood’s ability to clot can cause excessive bleeding (a haemorrhage).
Symptoms of excessive bleeding can include:
blood in your urine or faeces
prolonged nosebleeds (lasting longer than 10 minutes)
blood in your vomit
coughing up blood
Contact your GP immediately if you have any of these symptoms while taking an anticoagulant. If this is not possible.
Treatment during pregnancy
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 and some medications used to treat APS can harm an unborn baby.
If you do not plan your pregnancy, it may be several weeks before you realise you are pregnant, which may increase the risk of treatment to safeguard the pregnancy being unsuccessful.
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.
Treatment with aspirin and/or heparin is usually started at the beginning of the pregnancy and may continue for one to six weeks after you have given birth.
If you are diagnosed with APS, it is important that you take all possible steps to reduce your risk of developing blood clots. Effective ways of achieving this include:
eating a healthy, balanced diet that is low in fat and sugar and contains plenty of fruit and vegetables
taking regular exercise
maintaining a healthy weight and losing weight if you are obese(have a body mass index of 30 or more)
Complications of antiphospholipid syndrome (APS)
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. Symptoms may include:
loss of blood supply to the tips of your fingers or toes, causing them to go dark blue or black
swollen ankles, feet or hands
abdominal (tummy) pain
blood in your urine (haematuria)
coma (a state of unconsciousness where a person is unresponsive and cannot be woken up)
The symptoms usually develop suddenly and rapidly get worse.
Dial 999 and ask for an ambulance immediately if you or someone you know has APS which suddenly gets worse.
Immediate admission to an intensive care unit (ICU) is required for people with CAPS so that the body’s functions can be supported. High-dose anticoagulants are used to stop the blood clots getting bigger while they are slowly absorbed by the body.
However, 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.