Hughes syndrome
Introduction
Hughes syndrome, sometimes known as antiphospholipid syndrome, is a condition that can cause a wide range of symptoms, but is often not very well understood. The most common symptoms of Hughes syndrome are:
- blood clots within the veins and arteries
- problems with pregnancy, such as recurring miscarriages
Autoimmune condition
Hughes syndrome is an autoimmune condition, where the immune system attacks healthy tissue.
In Hughes syndrome, the immune system produces abnormal antibodies called antiphospholipid antibodies, which attack proteins and fats in the blood, including an important type of fat called phospholipid.
It is thought that these fats and proteins play an important role in keeping the blood at the right consistency. If the fats and proteins are attacked, the blood becomes abnormally "sticky". This is why people with Hughes syndrome have an increased risk of getting blood clots.
The blood clots can develop anywhere in the body, and trigger a number of potentially serious conditions, such as:
Blood clots can also adversely affect the development of an unborn baby during pregnancy, leading to miscarriages or premature births.
Types of Hughes syndrome
There are two types of Hughes syndrome:
Primary, where the condition develops in isolation and is unrelated to any other condition.
Secondary, where the condition develops in combination with another autoimmune condition, the most common of which is lupus.
How common is Hughes syndrome?
There is not enough reliable evidence to estimate how many people have Hughes syndrome.
Studies have found that an estimated 5% of all people have the antiphospholipid antibodies, but most do not develop any symptoms. The reasons for this are unclear.
There is evidence that Hughes syndrome is responsible for:
- one in five cases of DVT
- one in five cases of recurrent miscarriage (three or more)
- a fifth of cases of stroke in people under 45
Based on the information above, the Hughes Syndrome Foundation - the leading charity for people with Hughes syndrome - estimates that as many as 1% of people may have the condition.
The symptoms usually first develop between the ages of 18 and 40, although cases have been recorded in people of all ages, including children and babies.
The causes of Hughes syndrome are unknown, but like other autoimmune conditions, it is thought that both genetic and environmental factors may be responsible.
There is currently no cure. Treatment involves using anticoagulant medicines (medicines that thin the blood) such as warfarin to prevent blood clots.
Outlook
Despite being a potentially life-threatening condition, once treatment begins the outlook for Hughes syndrome is generally good. Most people with the condition respond well to anticoagulants and are able to lead normal, healthy lives.
Anticoagulants can also help to improve the outcomes of pregnancy, and an estimated 75-80% of women, upon being treated, will have a successful pregnancy.
Unfortunately, a small number of people with Hughes syndrome continue to experience blood clots despite having extensive treatment.
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Symptoms
The abnormal antiphospholipid antibodies that are produced by the immune system of people with Hughes syndrome can cause a wide range of symptoms that affect all parts of your body.
Some of the most common symptoms that are associated with Hughes syndrome are described below, although most people will not experience all of the symptoms listed.
Some of the most common symptoms that are associated with Hughes syndrome are described below, although most people will not experience all of the symptoms listed.
Deep vein thrombosis
Deep vein thrombosis (DVT) is one of the most common symptoms of Hughes syndrome. DVT is when a blood clot develops inside one of the larger and deeper veins in your body, usually inside the calf or thigh.
Symptoms of DVT include:
- pain, swelling and tenderness in one of your legs (usually the calf)
- 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
DVT usually affects only one leg. The pain may be worse if you bend your foot upward towards your knee.
One of the biggest risks is that the blood clot may move out of your leg and travel towards your lungs. If the blot clot reaches the lungs, it is known as a pulmonary embolism. See below for more information about pulmonary embolism.
Strokes and transient ischaemic attacks (TIA)
Stokes are one of the most serious symptoms that are associated with hughes syndrome. They develop when a blood clot blocks the supply of blood to the brain.
If you suspect that you or someone else is having a stroke, dial 999 immediately to call an ambulance.
The most effective way to identify the symptoms of a stroke is 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: the person’s speech may be slurred.
- Time: it is 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", is caused when a blood clot causes a temporary reduction, or blockage, of blood to the brain.
The symptoms of a TIA are the same as for a stroke, but they only last from between a few minutes to a few hours, before completely disappearing. However, you should never ignore a TIA because it is a serious warning sign that there is a problem with the blood supply to your brain.
Contact your GP if you, or someone else, has had a TIA. If this is not possible, contact your local hospital or out-of-hours service immediately to arrange for a specialist assessment.
Heart attacks
While heart attacks are less common than strokes, they are another very serious symptom associated with Hughes syndrome. A heart attack can occur when a blood clot forms in one of your coronary arteries (the blood vessels that lead to the heart). The blood clot blocks the blood supply to your heart.
Dial 999 immediately if you think that you, or someone you know, is having a heart attack. A heart attack requires immediate emergency treatment so do not wait to seek medical assistance.
The common symptoms of a heart attack are:
- crushing central chest pain, or mild chest discomfort
- shortness of breath
- clammy, sweaty and grey complexion
- dizziness
- nausea and vomiting
- restlessness
- coughing
- a general feeling of being unwell
- a frightening sense that one is about to die
Pulmonary embolism
Pulmonary embolism is a blood clot that occurs in one of the blood vessels of the leg. Most pulmonary embolisms are the result of a blood clot travelling from your leg up into your lungs.
Symptoms of a pulmonary embolism include:
- shortness of breath
- severe chest pain
- a persistent cough, which may bring up blood-stained phlegm.
Left untreated, a pulmonary embolism can be life-threatening. Contact your GP immediately if you suspect that you have one. If you cannot reach your GP, contact your local out-of-hours service or NHS Direct Wales (0845 46 47).
Pregnancy complications
Women with Hughes syndrome have a much higher risk of developing complications during their pregnancy, particularly if it is left untreated. These complications include:
- recurrent (three or more) early miscarriages, usually in the first 10 weeks of pregnancy
- one or more later-term miscarriages, usually after the 10th week of pregnancy
- premature birth, usually at or before the 34th week of pregnancy, which is often due to pre-eclampsia. This is a condition where a pregnant women suddenly experiences a rise in blood pressure.
Livedo reticularis
Livedo reticularis is a skin condition caused by small blood clots that develop inside the blood vessels of the skin.
Livedo reticularis causes the skin to take on a red or blue, blotchy appearance, and some people will also develop ulcers (sores) and nodules (bumps). The condition is often more severe in cold weather.
Superficial thrombophlebitis
Superficial thrombophlebitis is inflammation (swelling) of the veins that are located just under your skin, usually in your leg. The symptoms of the condition are similar to DVT, but they are not usually as severe. They include:
- swelling, redness and tenderness along the affected vein
- a high temperature (fever) of 38C (100.4F) or above, although this is less common
The symptoms of superficial thrombophlebitis usually resolve within two to six weeks.
Associated symptoms
There are a number of symptoms that are associated with Hughes syndrome that have been reported by many people with the condition. These include:
- migraine-like headaches, often associated with visual disturbances, such as seeing flashing lights, or zigzag patterns
- memory loss
- epilepsy, a condition that causes repeated seizures (fits)
- uncontrollable jerking of your limbs (chorea)
- multiple sclerosis-like symptoms, such as loss of balance, double vision, a feeling of pins and needles in your arms and legs, and difficulty walking.
It is thought that these symptoms may be due to the effects that antiphospholipid antibodies have on your brain.
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Causes
Antiphospholipid antibodies
The symptoms of Hughes syndrome are caused by antiphospholipid antibodies.
Antibodies are produced by your immune system and they are the hunter-killer cells of the body.
Antibodies identify threats to your body, such as bacteria and viruses, and signal to your immune system to release chemicals to kill the threat and prevent infection spreading.
In cases of Hughes syndrome, the immune system produces abnormal antiphospholipid antibodies, which, rather than attacking bacteria and viruses, mistakenly attack some of the fats and proteins found in your blood.
It is still not known exactly why the attack on the fats and proteins causes the blood to clot. However, the general consensus is that keeping your blood at the correct consistency (not too runny or sticky) is a delicate balancing act that relies on different types of proteins and fats working together.
By attacking these fats and proteins, the antiphospholipid antibodies disrupt the balance of the blood, causing it to become stickier and increasing the risk of blood clots developing.
Below are two important questions about Hughes syndrome that remain unanswered.
- What causes the immune system to produce the abnormal antibodies in the first place?
- Why do most people with the abnormal antibodies not experience any symptoms?
It is thought that the answers to both of these questions may be related to a combination of genetic and environmental factors.
Genetic factors
Research into the genetic factors that are related to Hughes syndrome is still at an early stage, but it seems that the genes that you inherit from your parents may play a role in the development of the abnormal antiphospholipid antibodies.
While Hughes syndrome is not passed down directly from parents to children in the same way that other conditions are, such as haemophilia and sickle cell anaemia, having a family member with antiphospholipid antibodies increases the chances that your immune system will also produce them.
A study that was carried out in 2008 found that almost half of people with Hughes syndrome had a similar mutated gene, known as the STAT4 gene.
The STAT4 gene is also thought to play a role in other autoimmune conditions, such as lupus (which causes symptoms of fatigue, skin rashes and joint pain) and rheumatoid arthritis (which causes joint pain and stiffness). This may explain why some people develop Hughes syndrome alongside another autoimmune condition.
Environmental factors
One suggestion to explain why only a small number of people with abnormal antiphospholipid antibodies go on to develop Hughes syndrome is that one or more environmental factors may be required to trigger the condition in susceptible people.
Environmental factors that may be responsible include:
- viral infections, such as the cytomegalovirus (CMV) or the parvovirus B19
- bacterial infections, such as e. coli (a bacteria that is often associated with food poisoning), or leptospirosis (an infection that is usually spread by rats, dogs, cattle and pigs, and causes flu-like symptoms)
- certain medications, such as anti-epileptic medicine or the oral contraceptive
Another theory is that many people with the abnormal antiphospholipid antibodies will only go on to develop symptoms of Hughes syndrome if they have additional risk factors for blood clots, such as:
However, this does not explain why some children develop Hughes syndrome because they do not usually have any of the risk factors listed above (with the possible exception of a lack of exercise and obesity).
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Diagnosis
The first stage in diagnosing Hughes syndrome is to test the blood for the abnormal antiphospholipid antibodies that cause the condition. Two tests are required with a six- to eight-week gap between them.
Two tests are required because harmless antiphospholipid antibodies can sometimes develop in the body for short periods of time, so it is necessary to confirm the result of the test at a later date. This can happen for a number of reasons, such as infection or as a side effect of certain medications, such as antibiotics. It is therefore necessary to confirm the result of the test at a later date.
The blood test that is used to diagnose Hughes syndrome is specifically designed to test for the condition. Hughes syndrome cannot be detected using routine blood tests.
Once the results of the blood tests have been confirmed, a careful assessment of your medical history will be carried out to determine whether you have had any previous symptoms that may be caused by Hughes syndrome.
A diagnosis of Hughes syndrome can usually be confirmed if you have had:
- one or more confirmed blood clots, and/or
- one or more unexplained late-term miscarriages (at, or after, the 10th week of your pregnancy), and/or
- one or more premature births at, or before, the 34th week of your pregnancy, and/or
- three or more unexplained early miscarriages (before the 10th week of pregnancy)
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Treatment
Your treatment plan
As there is currently no cure for Hughes syndrome, the aim of your treatment plan will be to reduce your risk of experiencing any further blood clots.
Additional treatment is also available during pregnancy that can help improve the chances of your pregnancy being successful. See below for more information.
Anticoagulant medication
As part of your treatment, you will be required to take anticoagulant medication. Anticoagulant medicines work by interrupting part of the process that is involved in the formation of blood clots.
This means that blood clots are less likely to form where they are not needed, but can still form when they are; for example, if you cut yourself and start to bleed. Two anticoagulant medications that are usually prescribed as a first option are:
If these prove to be ineffective in preventing further blood clots, you may either be given warfarin at a higher dose, or an additional anticoagulant medication called heparin.
Aspirin and warfarin are taken in tablet form (orally), and heparin is usually given as an injection (intravenously). You can be trained to administer the injections yourself.
Most people with Hughes syndrome will need to take anticoaguants for the rest of their life. A risk of these is that they can sometimes disrupt the blood’s ability to clot, which can cause excessive bleeding (haemorrhage).
Symptoms of excessive bleeding can include:
- blood in your urine or faeces (stools)
- black faeces (stools)
- severe bruising
- prolonged nosebleeds (that last longer than 10 minutes)
- blood in your vomit
- coughing up blood
Contact your GP immediately if you experience symptoms of excessive bleeding. However, if this is not possible, telephone your local out-of-hours service or NHS Direct Wales (0845 46 47).
Pregnancy
Women who are diagnosed with Hughes syndrome are strongly advised to plan for any future pregnancy. This is because treatment to improve the outcome of your pregnancy is most effective when it begins as soon as possible following an attempt to conceive.
If you do not plan your pregnancy, it may take several weeks before you realise that you are pregnant, which carries a small risk that treatment to safeguard the pregnancy may fail.
Treatment during pregnancy involves prescribing you daily doses of aspirin or heparin or a combination of both medications, depending on whether you have a history of blood clots and previous complications during pregnancy.
Warfarin should not be taken during pregnancy as it carries a small risk of causing birth defects.
Once you have reached the last three months of your pregnancy and the good health of your baby has been confirmed, you may no longer need to take heparin (though you may need to continue to take aspirin).
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Complications
Catastrophic antiphospholipid syndrome
An uncommon but very serious complication of Hughes syndrome is known as catastrophic antiphospholipid syndrome, which occurs in less than 1% of people with the condition.
In cases of catastrophic antiphospholipid syndrome, blood clots suddenly develop throughout the body, leading to multiple organ failure. It is unclear as to what exactly causes catastrophic antiphospholipid syndrome, although one in five cases occur after an infection, trauma or surgery.
Depending on which organs are involved, the initial symptoms of catastrophic antiphospholipid syndrome can be wide-ranging. Initial symptoms may include:
- fatigue
- swollen ankles, feet, or hands
- increasing breathlessness
- abdominal pan
- blood in your urine
- mental confusion
- seizures (fits)
- coma
Symptoms of catastrophic antiphospholipid syndrome usually develop suddenly and rapidly worsen.
It requires immediate admission to an intensive care unit (ICU) so that the body’s functions can be supported while the blood clots are treated with injections of high-dose anticoagulants.
If you have, or you know somebody with, Hughes syndrome and you suddenly notice a rapid deterioration in your (or their) condition, dial 999 to call an ambulance.
Unfortunately, even with the best available treatment, the outlook for catastrophic antiphospholipid syndrome is poor, with an estimated 50% of people dying as a result of the condition.
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Prevention
Reduce your risk of developing blood clots
If you are diagnosed with Hughes syndrome, it is important you take all possible steps to reduce your risk of developing blood clots.
The most effective way of doing this is by:
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