Antiphospholipid Syndrome

What is antiphospholipid syndrome?

Antiphospholipid syndrome (APS) is an autoimmune disorder, meaning that the body's immune system makes proteins known as antibodies that mistakenly attack its own cells or tissues. The syndrome is associated with risk of inappropriate blood clot formation, so it is considered an excessive clotting disorder (thrombophilia).

Antibodies normally defend the body against infections. But in APS, antibodies attack the lipid-proteins found in the outermost layer of cells (cell membranes) and platelets. These autoantibodies interfere with the blood clotting process in a way that is not fully understood. APS is associated with blood clots (thrombotic episodes), a low number of platelets (thrombocytopenia), and with pregnancy complications such as pre-eclampsia and recurrent miscarriages.

The primary antiphospholipid antibodies associated with APS include:

These antibodies increase the risk of developing recurrent inappropriate blood clots in both veins and arteries. Individuals with APS may experience one or more blood clots. Symptoms and complications may range from mild to critical.

If blood clots form, they can obstruct blood flow and can damage tissues and organs.
If blood clots are carried to the lungs, heart, brain or kidneys, they can cause a pulmonary embolism, heart attack, stroke, and/or kidney damage.
A small subset of people with APS may have widespread thrombotic disease with damage to many of the large internal organs of the body, referred to as "catastrophic" APS.

Antiphospholipid syndrome may affect anyone, but women of child-bearing age or those with lupus are more commonly affected. Antiphospholipid antibodies are found in 1% to 5% of the healthy general population. The incidence of antiphospholipid syndrome is reported to be about 5 cases per 100,000 persons per year, and its prevalence is reported to be about 40 to 50 cases per 100,000 persons. APS is the most common cause of strokes in people younger than 50 years of age. One out of 5 women who experience recurrent miscarriages have APS.

Individuals with antiphospholipid antibodies may have APS and another co-existing autoimmune disorder such as lupus or may have one or more of the antibodies present with no associated symptoms. Low levels of antiphospholipid antibodies may be associated with HIV, Lyme disease, and some cancers. APS can also be seen in the elderly and temporarily during infections and with some medications, such as the psychiatric drugs phenothiazines or the antibiotic amoxicillin and the heart rhythm regulator procainamide. Having a family member with antiphospholipid syndrome may also increase a person's risk.

About Antiphospholipid Syndrome

Signs, Symptoms and Complications
The first apparent sign that leads to a diagnosis of antiphospholipid syndrome may be the formation of a blood clot in a blood vessel (thrombosis), a clot that blocks the flow of blood flow to a vital organ (thromboembolism) such as a lung or the brain, or recurrent pregnancy loss.

Women with APS who become pregnant are at increased risk for complications such as deep vein thrombosis, pre-eclampsia, an underdeveloped placenta, premature childbirth, and pregnancy loss (miscarriage) but may not experience any signs or symptoms of the condition prior to becoming pregnant.

Health problems that are commonly associated with APS may include the following:

High blood pressure

Formation of blood clots in the legs (deep vein thrombosis, or DVT), which can travel to the lungs, causing a life-threatening pulmonary embolism

Strokes

Transient ischemic attacks (also known as "mini strokes"), which are caused by a temporary disruption of blood flow to the brain

Heart attack or chest pain caused by reduced blood flow to the heart (angina)

Skin conditions related to formation of clots in the vessels that supply blood to the skin, such as blotchy, lacy, bluish rash (livedo reticularis), skin ulcers, or the death (necrosis) of skin tissue

Bleeding from the nose and gums caused by a low platelet count (thrombocytopenia)

Less common signs and symptoms include the following:

Heart valve problems

Repeated headaches or migraines

Visual disturbances or vision loss

Balance and mobility problems

Difficulty concentrating or thinking clearly

Tests

The goals of testing are to diagnose APS and to distinguish it from other causes of symptoms and complications. Not everyone who has antiphospholipid antibodies has symptoms or complications. Therefore, a diagnosis of APS is made based upon both clinical signs and the presence of the autoantibodies. At least one clinical sign and one autoantibody must be present.

The following consensus guidelines are used:

Revised Classification Criteria for the Antiphospholipid Antibody Syndrome*
Clinical criteria	Laboratory criteria
Vascular thrombosis: One or more confirmed clinical episodes of a blood clot occurring in an artery, vein or small blood-vessel in any tissue or organ validated by imaging studies or tissue biopsy Pregnancy complications: One or more unexplained deaths of a physically normal fetus at or after the 10th week of pregnancy One or more premature births of a physically normal newborn at or before the 34th week of pregnancy due to pre-eclampsia, eclampsia, or a placenta that does not function properly Three or more unexplained consecutive miscarriages before the 10th week of pregnancy	Positive test for one of the autoantibodies on 2 or more occasions at least 12 weeks apart: Lupus anticoagulant: present, according to the guidelines of the International Society on Thrombosis and Hemostasis Anticardiolipin antibody: present at a medium or high level Anti-β2GP1antibody: present at a high level, greater than the 99th percentile for normal (as established by the testing laboratory)
*Established in 2006 by the 11th International Congress on Antiphospholipid Antibodies

Laboratory Tests

Blood tests that are used to detect the presence of autoantibodies include:

Lupus anticoagulant testing (e.g., dilute Russell viper venom test or DRVVT and hexagonal phase phospholipid neutralization test)
Cardiolipin antibodies
Beta2 glycoprotein I (β2GP1) antibodies

Other tests may be ordered to evaluate blood clotting and blood cells. They may include:

Partial thromboplastin time (PTT)
Prothrombin time (PT)
Complete blood count (CBC), to evaluate blood cells and platelets
A variety of additional tests to evaluate other causes of a person's symptoms, such as 1:1 Mix study (dilute PTT) to screen for lupus anticoagulant in the blood

Non-Laboratory Tests

Imaging scans may be performed to confirm the presence of and locate a blood clot, to evaluate organ damage, and, during pregnancy, to monitor a fetus. These may include:

CT scan
MRI
Ultrasounds to detect blood clots or to monitor fetal health and growth
Echocardiograph to detect heart valve abnormalities that can occur with APS

For more on these, see the web site RadiologyInfo.org.

Treatment

There is no cure for antiphospholipid syndrome (APS). The goals of treatment are to prevent blood clots from forming, resolve those that do, and to minimize tissue and organ damage. Those who have antiphospholipid antibodies but have never had a blood clot or miscarriage are not typically treated. They may never be diagnosed with APS or have associated symptoms or complications.

Individuals with APS should minimize other factors that increase clotting risk, such as smoking and the use of oral contraceptives. If a person has a co-existing autoimmune disorder, then this condition should be managed as well.

Anticoagulants such as warfarin and heparin are typically used to treat existing blood clots. To prevent blood clots from forming again, long-term anticoagulation with warfarin or an alternative anticoagulant is often necessary.

Women with APS can have successful pregnancies, but they and their fetus must be carefully monitored by a healthcare practitioner. Many may be given heparin injections beneath the skin (subcutaneous) and/or low-dose aspirin during pregnancy to help minimize the potential for clotting. Warfarin cannot be used in pregnancy.

For people with "catastrophic" APS, a combination of anticoagulant, glucocorticoid, and plasma exchange treatment with or without intravenous immune globulin is required. Additional treatments may be required to address a low number of platelets (thrombocytopenia) and other APS complications.

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