• Anti-phospholipid syndrome (APS)

    Antiphospholipid syndrome, often referred to as APS, is sometimes known as sticky blood syndrome or Hughes Syndrome after a doctor who researched and published widely on the condition in the early 1980s. APS can cause blood clotting in the arteries or veins and is also a major cause of recurrent miscarriage. It’s also one of the most common causes of strokes in young people. It’s estimated that 1 in 5 people who’ve had a stroke before the age of 40 may have APS.

    APS affects all age groups but is most common between the ages of 20 and 50. It was first diagnosed in people who had lupus (systemic lupus erythematous) but it was later discovered that APS can exist in people who don't have lupus or any other disease. APS that exists on its own is called primary APS.

  • Symptoms of APS

    The two main problems caused by APS are blood clotting and pregnancy problems, particularly recurrent miscarriage. Blood clotting can occur:

    • In the veins, causing pain and swelling, typically in the calf (deep vein thrombosis or DVT) – this can sometimes lead to pulmonary embolism if a piece of the clot breaks away and travels to the lung
    • In the arteries, causing high blood-pressure or strokes
    • In the brain, can cause memory loss, migraines, forgetfulness, slurred speech, fits or sight problems

    In pregnancy, APS can cause repeated miscarriage. This can happen at any time during the pregnancy but is most common between 3 and 6 months. APS can also cause other pregnancy complications, such as high blood pressure (pre-eclampsia), small babies and early deliveries. APS is now recognized as one of the most important causes of treatable recurrent miscarriages.

    Other problems sometimes associated with APS include:

    • Heart problems: the heart valves may thicken and fail to work, or the arteries may narrow because their walls get thicker, leading to angina
    • Kidney problems: APS can cause narrowing of the blood vessels, including those serving the kidneys, resulting in high blood pressure
    • Infertility: testing for antiphospholipid antibodies is becoming routine in infertility clinics
    • Skin problems : some people develop a blotchy rash, often seen on the knees or arms and wrists, with a lacy pattern (known as livedo reticularis)
    • Low platelet count : platelets are small cells in the blood which are involved in the control of bleeding. Some people with APS have very low platelet levels – often there are no symptoms, although people with very low counts may bruise easily or experience strange or excessive bleeding

    Very rarely, APS can cause clots to develop in small blood vessels in several parts of the body at once, causing damage to several organs at the same time and making you seriously ill. This is called catastrophic APS and is very rare.
    It’s thought to be triggered by things like infection, trauma, medication or surgery. You should have quick and easy access to your rheumatology or hematology team in these circumstances.

  • Epidemiology and cause of APS

    All age groups can be affected, from infants to the elderly, but most people with APS are aged between 20 and 50 years. It seems to affect the health of women more than men because of its effect in pregnancy.

    APS is an autoimmune disease, which means that it’s caused by your immune system attacking parts of the body and producing symptoms.

    If you have APS, your immune system produces harmful antibodies called antiphospholipid antibodies (aPL). These aPL attack proteins linked to fats in your body. The most important of these proteins is called beta-2-glycoprotein I. When aPL stick to this protein they can interfere with blood cells. The cells change in such a way that the blood becomes 'sticky' and more likely to clot inside the vessels. In a pregnant woman aPL can also affect the cells of the womb and the placenta, which can make the baby grow more slowly and increase the risk of miscarriage.

    Although people with APS have a higher risk of thrombosis than other people, this doesn’t mean that they suffer clots all the time. In fact, they may go for many years without suffering clots. The risk can be reduced by certain drugs and by reducing or monitoring other factors that can cause clots, including:

    • Smoking
    • Keeping still for long periods (linked, for example, to the thrombosis seen after long-haul flights)
    • The contraceptive pill
    • Genetic factors – there may be a family history of clots, miscarriages, other autoimmune diseases such as lupus, or thyroid problems.
    • Occasionally, the thrombosis occurs during an infection such as a sore throat; however, in the vast majority of people the thrombosis comes ‘out of the blue’.

  • Outlook of APS

    Many people with APS feel very well and have no symptoms. The aim of treatment is usually to prevent thrombosis or miscarriage. This is achieved by an early diagnosis and the right combination of drugs. Other people with APS have symptoms like rash, joint pain, migraine and tiredness even when they don’t suffer thrombosis and are not pregnant. This is especially true in people who have lupus as well as APS.

    Because these drugs are being used to prevent symptoms rather than to treat them after they happen, it means that you may be taking drugs for many years without having symptoms. These drugs can have side-effects so it’s critical to balance the risk of suffering APS symptoms against the risk of side-effects.

    In summary, the outlook for most patients with APS is good but it’s important to use the right drugs and to be aware of the side-effects.

  • Diagnosis of APS

    APS can only be diagnosed if you have a positive blood test and you have suffered either thrombosis or a miscarriage. More and more people who have thrombosis or a miscarriage are routinely tested for APS. If you’ve had either of these problems, especially if they’ve happened more than once, you should discuss with your doctor whether you need these blood tests. Depending on the results, your doctor may want to refer you to a specialist (either a rheumatologist or a hematologist).

  • Laboratory test for APS

    There are three main blood tests used to diagnose APS. These are:

    • The anticardiolipin test
    • The lupus anticoagulant test
    • The anti-beta-2-glycoprotein I test

    All three tests detect whether aPL are present in the blood. The result of the lupus anticoagulant test is either positive or negative, and the results of the other two tests are given as numbers. The higher this number is, the more aPL a person has in their blood. Although these tests all measure aPL, they do so in different ways so that around 20% of people with APS will have a negative result in one test or the other. One test alone could miss the diagnosis.

    The tests are usually repeated after 12 weeks as levels of aPL vary and can sometimes go up when you have an infection. If you only have one positive test and it quickly becomes negative again then you probably don’t have APS.

    Higher levels of antibodies (i.e. higher numbers in the anticardiolipin or anti-beta -2-glycoprotein I tests) suggest you may be at greater risk of blood clots and other symptoms. Being positive in more than one of the three tests also suggests a higher risk.

  • Repeatedly test for aPL is positive. Does this mean I’ll definitely get APS

    No, this doesn’t mean that you’ll definitely get APS. In fact, many people who have lupus are tested for these antibodies as part of their routine lupus blood tests and about 20–30% will be positive for aPL. People who carry the antibodies but who’ve never had either clots or miscarriages are not said to have APS. They are aPL-positive people without symptoms, and doctors have to decide whether they’re at high or low risk of getting APS in the future. There’s no foolproof way of deciding, but factors that may help include:

    • How high the aPL level is
    • How many of the three tests are positive
    • Whether there are other risk factors for thrombosis
    • Whether you have other typical symptoms of APS (such as migraine)
  • Is the test is for lupus

    No, this confusion often arises because one of the blood tests for APS is called the 'lupus anticoagulant' test. This is because it was first invented by doctors who were studying patients with lupus. In fact it is a test for APS, NOT a test for lupus. There are other, better blood tests for lupus itself and many people who are positive in the lupus anticoagulant test do not have lupus.

  • Treatment options for APS

    Drugs

    • At present APS cannot be cured, but the effects can be controlled. For example, treatment with anticoagulant (blood-thinning) drugs can help prevent both blood clots and miscarriages. The most commonly used drugs are aspirin, warfarin and heparin
    • If you have aPL but no history of clotting, your doctor will probably recommend daily low-dose aspirin (75–100 mg)
    • This isn’t guaranteed to prevent blood clots but is known to make the blood less 'sticky'. If you have other factors which increase your risk, for example a family history of clots, or if you suffer from typical APS symptoms such as migraine or livedo reticularis, your specialist may advise you to take warfarin instead of aspirin. It’s very important to do whatever you can to reduce your own risk of clots (see section Self-help and daily living)
    • If you have APS and a history of clotting , you’re likely to be given warfarin to prevent further blood clots. Warfarin is taken by mouth. You’ll have regular blood tests (this is called an INR) to check what effect the drug is having, and if necessary your dose will be adjusted. The INR blood tests can be just a finger-prick test or a more formal assessment by a laboratory. The most serious side- effect of warfarin during treatment is bleeding. This means that your dosage will be closely monitored
    • Warfarin can interact with a number of drugs and foods (for example grapefruit juice), and so it’s important that you’re aware of this and take steps to ensure your other medications or diet won’t affect the results of the blood tests
    • If you’ve had a number of miscarriages but no history of clotting, there are two considerations – treatment during pregnancy to prevent another miscarriage and treatment outside pregnancy to prevent clots. During pregnancy the usual treatment is low -dose aspirin; however, it’s common for pregnant women with APS to be given daily injections of heparin as well as aspirin, especially if the previous miscarriages happened in mid- to late pregnancy or if there have been other pregnancy complications such as pre- eclampsia. It’s a good idea to be seen in a special pregnancy clinic where the doctors have experience of APS, as well as by your normal obstetrician. Most APS specialists have access to these clinics and you should ask about this if you’re planning to get pregnant
    • If you’ve suffered miscarriages and have APS you may have an increased risk of clots as well, even when you’re not pregnant, so you may be advised to take low-dose aspirin even after your baby is born
    • If you’re on warfarin and you become pregnant you’ll probably be changed over to heparin. This is because warfarin is potentially harmful to the baby
    • Even with treatment, complications can sometimes occur towards the end of pregnancy. However, advances in the understanding and treatment of APS have resulted in many more successful pregnancies in women with the condition. With close monitoring of the pregnancy, there’s now a very good chance that your baby will do very well with no long-term problems
  • Self-help and daily living

    • Exercise - Although there aren’t any specific exercises that can help with the condition, taking regular exercise will help keep you fit and keep your heart healthy
    • Diet and nutrition - It’s been suggested that increasing the amount of essential fatty acids in your diet, particularly omega-3 fatty acids found in oily fish, could help reduce the risk of thrombosis. However, there are no clinical trials to support this idea
    • As well as this, fish oils contain large amounts of vitamin A which can be harmful in pregnancy, so we wouldn’t recommend this if you’re thinking of having a baby. Eating a healthy, balanced diet is important for your general health and may help prevent you from developing blood clots. You should also keep to a healthy weight and stop smoking. At present, no complementary medicine has been shown to help with APS.

      There are several things that you can do to help reduce the risk of getting clots:

    • Don’t smoke – smoking will increase your risk of clots
    • Don't drink excessive amounts of alcohol
    • Think very carefully about what sort of contraception to use and discuss it with your doctor, as some types of contraceptive pill increase the risk of clotting
    • If you’re thinking about hormone replacement therapy after the menopause, this may also increase your risk of clots so you should discuss it with your doctor
    • Think ahead if you know you’ll soon have to keep still in one place for a long time (for example on a long-haul flight). It may be possible to get your travel agent to book you a seat with room to stretch your legs, and some people like to wear elasticated stockings during the flight to reduce the risk of clots building up in the lower legs. Ask your specialist whether this would be good for you
    • If you have another condition that can increase your risk of blood clots (e.g. diabetes, high blood pressure or high cholesterol) you should make sure you have regular checks to keep these factors under control
  • Helping yourself with APS

    It’s always important that you understand the features of APS and therefore when to ask for help. You should have access to your local specialist team, which may include a specialist nurse who you can call for advice.

    If you’re taking drugs such as warfarin you should be careful about accidents, as bruising can be worse. If you’re pregnant it’s important that you attend your clinic appointments and keep in touch with your specialist obstetric consultant, whose aim is always to keep you and your baby healthy.

  • Glossary

    Angina –Severe chest pain characterized by a choking or crushing sensation below the breastbone. It occurs when the heart muscle isn’t receiving enough oxygen.
    Anti-beta-2-glycoprotein I test – A blood test used to diagnose APS. This test measures the amount of anti-beta-2-glycoprotein I antibodies in the blood.
    Antibody – A naturally occurring molecule produced by the body to combat infections.
    Anticardiolipin test – A blood test used to diagnose APS. This test measures the amount of antiphospholipid antibodies in the blood.
    Antiphospholipid antibody (aPL) -An antibody which attacks proteins in the phospholipids (see below). Because the antibody attacks the body’s own cells, rather than bacteria, it’s called an auto-antibody.
    Autoimmune disease (intervertebral disc) –A disorder of the body’s defense mechanism (immune system), in which antibodies and other components of the immune system attack the body’s own tissue – these are called auto-antibodies.
    Beta-2-glycoprotein I – A protein in the blood, which attaches itself to phospholipids in the walls of blood cells. When aPL and beta-2-glycoprotein I joined together attach to phospholipids it causes changes in the cells, which leads to clotting.
    Deep vein thrombosis – A blood clot that forms in the deep-lying veins (usually in the leg or pelvis).
    Hematologis – A hospital specialist who has an interest in disease of the blood.
    Immune system –The tissues that enable the body to resist infection. They include the thymus (a gland that lies behind the breastbone), the bone marrow and the lymph nodes.
    Livedo reticularis – A rash which occurs in APS. It looks blotchy and is seen most often on the knees and wrists. It gets its name because of its lacy pattern on the skin.
    Lupus – A short name for systemic lupus erythematous, a condition often linked to APS.
    Lupus anticoagulant test – A blood test used to diagnose APS. This test measures the effect of the anti-phospholipid antibodies on the blood clotting time. It's not a test for diagnosing lupus.
    Obstetric consultant – a doctor who specializes in helping women who have medical problems during pregnancy.
    Phospholipids –A type of fat found throughout the body, particularly in the outer coating of cells or cell membrane.
    Placenta – an organ within the womb that provides nourishment to the developing baby. The placenta is discharged after the baby is born and is sometimes known as the afterbirth.
    Pre-eclampsia –A common condition in the second half of pregnancy in which three things occur: high blood pressure, protein in the urine and fluid retention. Pre-eclampsia occurs more commonly in first pregnancies as well as APS.
    Pulmonary embolism – The blockage of the pulmonary artery or one of its branches in the lungs, usually caused by detached fragments from a blood clot in a leg or pelvic vein.
    Rheumatologist - A hospital specialist with an interest in diseases of joints, bones and muscles. As lupus is one of the conditions treated by rheumatologists, they often have an interest in APS.
    Thrombosis – A blood clot which may occur in an artery or a vein.
    Warfarin – A drug used to prevent blood clots from forming or growing larger.
    It works by thinning the blood, making it less ‘sticky’ and reducing the blood’s ability to clot.