What Is Antiphospholipid Syndrome (Hughes Syndrome)? What Causes Antiphospholipid Syndrome?

Antiphospholipid Syndrome, also known as Antiphospholipid Antibody Syndrome, APS, APLS, Hughes Syndrome, or Sticky Blood is an immune disorder in which there are abnormal antibodies linked to abnormal blood clots within veins and arteries - especially in the legs, as well as problems with pregnancy, such as recurring miscarriages and premature births. The abnormal antibodies attack fats that contain phosphorous (Phospholipids). Approximately 1 in every 3 patients with antiphospholipid syndrome has heart valve abnormalities.

Patients more commonly develop DVT (deep vein thrombosis) - blood clots that form in the legs; however, clots may also form in the kidneys, lungs and other organs. If a clot develops in the brain there is a serious risk of stroke.

There is no cure for Hughes Syndrome. However, current treatments may significantly reduce the patient's risk of developing blood clots.

Antiphospholipid syndrome is an autoimmune condition - the person's immune system produces antibodies called antiphospholipid antibodies. These are abnormal antibodies, which attack proteins and fats in the blood; specifically phospholipids. The fats and proteins that are attacked are thought to play an important role in maintaining proper blood consistency. By attacking these proteins and fats the blood becomes excessively sticky, resulting in a significantly higher risk of developing blood clots.

There are two main types of antiphospholipid syndrome (Hughes syndrome):

• Primary antiphospholipid syndrome - the condition is not linked to any other disease or condition. It develops in isolation.
• Secondary antiphospholipid syndrome - the condition develops along with another autoimmune disorder, such as lupus.

Statistics USA - according to the APS Foundation of America, Inc.:

• Between 1% and 5% of the American population is believed to have APS antiphospholipid syndrome (APS).
• Between 15% and 20% of all cases of DVT (deep vein thrombosis) and pulmonary embolisms (lung blood clots) are caused by APS.
• Between 10% and 25% of women with recurrent miscarriages have APS.
• Approximately 1 in every 3 cases of stroke among people under 50 years of age is due to APS.
• Between 75% and 90% of patients with APS are female.
• Between 40% and 50% of individuals with lupus also have APS.

Statistics UK - according to the National Health Service (NHS), UK:

• It is estimated that approximately 5% of the UK population have antiphospholipid antibodies, but the majority never have any symptoms. Nobody is sure why.
• Antiphospholipid syndrome is responsible for 1 in every 5 cases of DVT (deep vein thrombosis)
• APS is responsible for 1 in every 5 cases of recurrent miscarriages.
• APS is responsible for 1 in every 5 cases of stroke among patients under 45 years of age.
• The Hughes Syndrome Foundation (UK) estimates that as many as 1% of the population of England may have antiphospholipid syndrome.

Typically, those who develop symptoms will do so between the ages of 18 and 40 years. However, sometimes they may develop very early on during childhood.

The majority of patients with antiphospholipid syndrome who receive treatment are able to lead normal and healthy lives. Approximately 75% to 80% of women with antiphospholipid syndrome who receive treatment are able to have healthy, full-term pregnancies.

In some rare cases people with antiphospholipid syndrome continue to develop blood clots, despite receiving treatment.

According to Medilexicon's medical dictionary:

Primary antiphospholipid syndrome (PAPS) is "a thrombophilic state characterized by recurrent arterial and venous thrombosis, recurrent pregnancy loss, and the presence of circulating antiphospholipid antibodies (anticardiolipin and anti-B2-glycoprotein I antibodies)."

What are the signs and symptoms of antiphospholipid syndrome?

A symptom is something the patient senses and describes, while a sign is something other people, such as the doctor notice. For example, drowsiness may be a symptom while dilated pupils may be a sign.

Signs and symptoms of antiphospholipid syndrome depend mainly on where the blood clots travel to, and where they form. A clot or embolus (travelling clot) can result in:

• DVT (deep vein thrombosis) - occurs when a blood clot forms in one of the large veins, usually in the arm or leg, leading to either partially or completely blocked circulation. A DVT blood clot has the potential to move into the lungs, creating a life-threatening condition known as a Pulmonary Embolism.
  
  
• Pulmonary embolism (PE) - a condition where an object called an embolus (travelling clot) is created in one part of the body, circulates throughout the body, and then blocks blood flowing through a vessel in another part of the body. Emboli (plural of embolus) are not to be confused with thrombi (plural of thrombus), which are clots that are formed and remain in one area of the body without being carried throughout the bloodstream. A pulmonary embolism (pulmonary meaning "of the lungs" from the Latin pulmōnārius) occurs when an embolus blocks blood flowing through an artery that feeds the lungs.
  
  
• Complications of pregnancy - including recurring miscarriages, premature delivery, and preeclampsia (high blood pressure during pregnancy)
  
  
• Stroke - a condition where a blood clot or ruptured artery or blood vessel interrupts blood flow to an area of the brain. A lack of oxygen and glucose (sugar) flowing to the brain leads to the death of brain cells and brain damage, often resulting in impairment in speech, movement, and memory. The two main types of stroke include ischemic stroke and hemorrhagic stroke. Ischemic stroke accounts for about 75% of all strokes and occurs when a blood clot, or thrombus, forms that blocks blood flow to part of the brain.

The following signs and symptoms are also possible (less common):

• Chronic (long-term) headaches
• Dementia and seizures if a clot blocks blood flow to parts of the brain
• Livedo reticularis - a rash develops on the knees and wrists. The rash appears as a lace-like purplish discoloration.
• Migraines

Heart valve abnormalities - about one third of all patients with antiphospholipid syndrome have heart valve problems. In many cases the mitral valve thickens, or develops extra mass, causing regurgitation (blood leaks back into one of the heart's chambers). Some patients may have problems with the aortic valve.

Drop in platelets - platelets are blood cells needed for normal clotting. If levels drop enough (thrombocytopenia) there may be episodes of bleeding. Patients typically experience nosebleeds, or their gums bleed. Some patients may develop petechiae (bleeding into the skin, causing small red spots to appear).

The following signs and symptoms possible, but extremely rare:

• Chorea - the body and limbs jerk uncontrollably. Sometimes they may appear as non-stop rapid and complex body movements that are well coordinated - but they are unintentional.
• Memory problems
• Some mental health problems, such as depression or psychosis (a thought disorder in which reality testing is severely impaired).
• Unexpected loss of hearing.

When to seek medical help

• Possible deep vein thrombosis - there is pain, tenderness, swelling, discoloration of a vein. The skin is warm to the touch. Seek emergency care.
  
  
• During the first 20 weeks of pregnancy - if there is any vaginal spotting. This could be a sign of a miscarriage (but not necessarily). Ask your doctor whether antiphospholipid syndrome is possible.
  
  
• Stroke - signs include dizziness, trouble walking, loss of balance and coordination, speech problems, numbness, weakness or paralysis on one side of the body, blurred/blackened or double vision, sudden severe headache.
  
  
• Pulmonary embolism - chest pain, increased or irregular heartbeat, dizziness, sudden shortness of breath, rapid breathing, cough, or coughing up blood.

What are the risk factors for antiphospholipid syndrome?

A risk factor is something which increases the likelihood of developing a condition or disease. For example, obesity significantly raises the risk of developing diabetes type 2. Therefore, obesity is a risk factor for diabetes type 2. The risk factors for antiphospholipid syndrome include:

• Having lupus, Sjogren's syndrome, or some other autoimmune disorder.
  
  
• Hepatitis C, syphilis, cytomegalovirus (CMV), the parvovirus B19 and some other infections.
  
  
• Some medications, including hydralazine (used to treat hypertension) and some anti-epileptic drugs.
  
  
• Genetics - people who have a family member with antiphospholipid syndrome have a higher risk of developing it themselves, compared to people who don't.
  
  
• Gender - young and middle-aged women are more likely to develop antiphospholipid syndrome than males. However, both sexes can be affected, as well as people of any age.

Some people may have the antibodies that are linked to antiphospholipid syndrome, but never develop signs or symptoms. People with these antibodies are more likely to develop symptoms if they:

• Are obese
• Become pregnant
• Have high cholesterol levels
• Have hypertension (high blood pressure)
• Receive HRT (hormone replacement therapy)
• Smoke tobacco
• Stay still for too long, as may be the case during a long-haul flight
• Take oral contraceptives
• Undergo a surgical procedure

What are the causes of antiphospholipid syndrome?

What are phospholipids?

When we bleed our blood eventually clots (coagulates) to stop us from losing too much blood. Phospholipids are one of the substances involved in the blood-clotting process - a complex process involving several steps. Phospholipids are cell membrane substances.

People with antiphospholipid syndrome produce antibodies which attack either the phospholipids or blood proteins which bind to the phospholipids.

What is an autoimmune disorder?

Antibodies are produced by our immune system to fight off and destroy germs and toxins which our bodies do not want - they identify potential threats to the body and destroy them. If somebody has an autoimmune disorder, they have antibodies which mistakenly attack good cells - in the case of antiphospholipid syndrome abnormal antiphospholipid antibodies are produced, which mistakenly attack phospholipids.

What happens if phospholipids are attacked?

If phospholipids are attacked there may be a significantly greater risk in developing blood clots. Experts are not sure why, but they say that we must keep the consistency of our blood just right - it must be neither too sticky nor too runny. This delicate balance depends on several proteins and fats working simultaneously. If the balance is disturbed and the blood becomes stickier, which may happen if phospholipids and some other proteins are attacked, the risk of blood clots developing grows.

We don't know why the immune system produces the abnormal antibodies. Neither do we understand why some people with abnormal antibodies never develop any antiphospholipid syndrome symptoms. Experts believe a combination of genetic and environmental factors are involved.

Diagnosing antiphospholipid syndrome

A doctor will test for antiphospholipid syndrome if the patient has at least one episode of thrombosis, or a pregnancy loss.

Blood test - this will determine whether the abnormal antibodies are present. Two tests are involved, several weeks apart. Sometimes harmless antiphospholipid antibodies may develop for limited periods, because of an infection or some medication. That is why a second test is required at a later date.

If the blood tests confirm the presence of abnormal antibodies, the doctor will make a careful assessment of the patient's medical history to determine whether previous symptoms may have been caused by antiphospholipid syndrome.

A diagnosis of antiphospholipid syndrome will be confirmed if (National Health Service, UK):

The patient had at least one confirmed blood clot
Or
At least one unexplained late-term miscarriage (tenth week of pregnancy onwards)
Or
At least one premature birth by the 34^th week of pregnancy
Or
At least three unexplained early miscarriages that occurred before the tenth week of pregnancy

What are the treatment options for antiphospholipid syndrome?

As the main problem is sticky blood, doctors will usually prescribe medication that thins the blood - reduces the blood's propensity to clotting, such as low-dose aspirin.

Aspirin plus Warfarin, and possibly Heparin - aspirin together with Warfarin are generally prescribed as a first option. If this combination does not work, the patient may either be prescribed a higher Warfarin dose, or an additional drug - heparin - will be given.

Aspirin and Warfarin are taken by mouth (orally) in tablet form, while heparin is usually injected. Patients can be taught how to administer the heparin themselves. Patients will have to take anticoagulant medication for the rest of their lives.

Anticoagulants may sometimes undermine the blood's ability to coagulate, resulting in hemorrhage (excessive bleeding). Signs and symptoms of excessive bleeding include:

• Blood in stools (feces)
• Blood in urine
• Blood in vomit
• Coughing up blood
• Nosebleeds that last longer than ten minutes
• Severe bruising

Patients taking anticoagulants who experience any of these symptoms should tell their doctor immediately.

Thrombosis treatment - Heparin combined with Warfarin are usually prescribed for the treatment of thrombosis. When that is cleared the patient with antiphospholipid syndrome will continue with Warfarin for the rest of his/her life. Sometimes the doctor may recommend Warfarin along with low-dose aspirin.

Pregnancy - women who have already been diagnosed with antiphospholipid syndrome will be advised by their doctors to plan for pregnancy. For treatment to be really effective it must start soon after any attempt to conceive. If the pregnancy is unplanned treatment may not begin until several weeks after conception.

Pregnant patients with antiphospholipid syndrome are usually given aspirin, heparin or both. This will depend on whether they had previous pregnancy complications, and/or blood clots. Warfarin, which can cause birth defects, is not used during pregnancy.

If the pregnant mother and baby reach the third trimester in good health, the heparin treatment may stop. The mother may have to continue taking aspirin right up the end of her pregnancy.

The pregnant mother will be monitored closely with blood tests to make sure her blood can still coagulate (clot) enough to stop bleeding if she bruises or cuts herself.

What are the complications of antiphospholipid syndrome?

Catastrophic antiphospholipid syndrome - estimated to affect less than 1% of patients with antiphospholipid syndrome. Blood clots abruptly develop all over the body, resulting in multiple organ failure. 20% of cases occur after trauma, surgery or an infection. However, experts are not sure why catastrophic antiphospholipid syndrome occurs. Symptoms vary, depending on which organs are affected, and may include:

• Abdominal pain
• Coma
• Confusion
• Edema (swelling) in the extremities (ankles, feet or hands)
• Fits (seizures)
• Progressive breathlessness
• Tiredness

Symptoms typically appear suddenly and get worse rapidly. Catastrophic antiphospholipid syndrome is a medical emergency and the patient needs to get into an ICU (intensive care unit) as soon as possible so that the body's functions can be maintained while high-dose anticoagulants are administered. Unfortunately, even with the best medical care in the word, 50% of patients with catastrophic antiphospholipid syndrome do not survive.

Prevention

A patient with antiphospholipid syndrome needs to take all possible measures to lower the risk of developing blood clots. To do this, it is important:

• Not to smoke
• To eat plenty of fruit and vegetables
• To follow a diet which is well-balanced and low in fat and sugar
• To maintain a healthy bodyweight. Obese and overweight patients should seriously consider losing weight.
• To remain physically active