What is antiphospholipid syndrome?

Antiphospholipid syndrome (APS), also known as antiphospholipid antibody syndrome (APLS), is an autoimmune inflammatory disease that causes abnormal blood clot formation in a person’s arteries and veins.

Blood clotting (thickening of the blood) is a normal function of the body. When an injury cuts a person's skin, a blood clot stops the bleeding. But internal blood clots that form inside the blood vessels are dangerous, and the overactive blood clotting associated with APS can cause life-threatening health problems.

Antiphospholipid syndrome was first discovered in the 1980s.

What are the symptoms of antiphospholipid syndrome?

APS symptoms include blood clots in the arms or legs, low platelet counts in the blood, and heart valve abnormalities. Many other symptoms can appear because of conditions caused by blood clots. Some patients may have only one of these symptoms, while others may have several of them. These include:

• Swelling or warmth in the arms or legs.
• High blood pressure.
• Lace-like or marbled rash (livedo reticularis), especially in the arms or legs.
• Dizziness, headaches, dementia or problems with vision, hearing or memory (any of which can arise due to stroke, when a blood clot blocks or reduces blood flow to parts of the brain).
• Jerky, involuntary body movements (chorea).

Blood clots from APS can create life-threatening conditions that include deep vein thrombosis, pulmonary embolism, pregnancy loss (miscarriage), heart attack, stroke, and kidney disease. Less than 1% of APS patients experience what is called “catastrophic APS” (CAPS), where multiple blood clots form in small, medium and large blood vessels over a short period of time (usually within a week). This life-threatening condition requires immediate hospitalization in an intensive care unit (ICU). The risk of blood clots increases whenever any patient is recovering from surgery. For this reason, a person who has APS must take special precautions before having any kind of surgical procedure.

About 70% to 80% of APS patients are women. APS is more common among Caucasians and those of Asian descent than in those of African descent. It is not known why. APS can occur on its own, but it is often found in patients who have other autoimmune disorders, especially systemic lupus erythematosus (commonly known as "lupus").

The immune system and APS

A healthy immune system helps the body fight disease. It makes proteins called antibodies that identify and attack substances that enter the body and which might cause harm. Any substance that causes a person’s immune system to make antibodies is called an antigen. Many antigens, such as certain viruses or bacteria, are a threat to health. But some people's immune systems attack antigens that are harmless to most other people (such as flower pollen, pet hair or peanuts in people with allergies).

In an autoimmune disease (also called an autoimmune disorder), the immune system misidentifies a substance that naturally occurs inside the body as a threat. It then makes antibodies to fight these substances (called autoantigens). In other words, the body attacks itself.

In antiphospholipid syndrome, the immune system makes an antibody called antiphospholipid (aPL). The aPL antibody attacks some parts of normal human cells, including phospholipids, which are fats that form the main building block of cell membranes.

How is antiphospholipid syndrome diagnosed?

A conclusive diagnosis requires at least two blood tests, spaced three or more months apart. Because many of its signs and symptoms are also caused by other, more common conditions, it can be difficult for a physician to recognize, and so many patients may go untested and undiagnosed for years. For example, most headaches, heart attacks or miscarriages are caused by health problems unrelated to APS. Adding to this confusion, people with APS sometimes receive false-positive test result for syphilis, a sexually transmitted disease.

Patients who have a low platelet count and show any other signs of APS should be thoroughly tested, as should women who experience multiple miscarriages. A conclusive diagnosis can be made only when a patient gets positive results from at least two blood tests, spaced three months or more apart from one another. The most common blood tests used to diagnose APS are lupus anticoagulant (LA), anticardiolipin antibody (aCL) and anti-beta2-glycoprotein 1.

How is antiphospholipid syndrome treated?

Patients with APS who develop blood clots are usually placed on a long-term plan of anticoagulant medications (commonly called “blood thinners”), such as aspirin, warfarin, or heparin. Pregnant women with antiphospholipid syndrome are usually treated with heparin. This treatment gives a fetus an 80% to 90% chance of survival, although it will likely be born several weeks premature. Left untreated, a fetus has only about a 20% chance of survival.

Other medications used to treat APS include:

• Corticosteroids, such as prednisone.
• Hydroxychloroquine. (Traditionally used to prevent and treat malaria, this drug can reduce blood clotting in some APS patients.)
• Intravenous immunoglobulin (IVIG) infusion therapy, in which antibodies obtained from multiple healthy blood donors are injected into the patient.
• Statins. Traditionally used to lower cholesterol and prevent heart disease, these drugs have been shown to reduce certain proteins that are elevated in APS patients and which create an increased risk of blood clots.

Treatment for APS at Hospital for Special Surgery

HSS physicians are some of the top APS specialists in the world, and HSS is the leading center for the APS ACTION International Clinical Database and Repository. This international research network does clinical studies on antiphospholipid syndrome. It has also created a secure, web-based clinical database of patients whose APS symptoms and progress can be followed over a 10-year period. Patient participation in this research is free and voluntary. Participants are offered genetic testing specific to APS, as well as counseling for special situations (such as long flights, surgery) to avoid cardiovascular disease and blood clot prevention. The anonymous APS data that participants provide helps the medical community better understand APS and treat patients in the future.