A “syndrome” is a collection of signs and symptoms that are characteristic of a particular disorder. Antiphospholipid syndrome (APS, and also sometimes referred as antiphospholipid antibody syndrome), is a complex condition that is so named because its symptoms are caused by a dysregulated immune system that attacks the natural and healthy phospholipids produced in a person’s body.
Antiphospholipid syndrome is a systemic autoimmune inflammatory disorder in which a person’s immune system makes antibodies that can cause the formation of blood clots in the blood vessels as well as pregnancy problems. Blood clotting (thickening of the blood) is a normal function of the body. It is what stops the bleeding when we get a cut. But blood clots that form inside the blood vessels are dangerous, and the overactive blood clotting associated with APS can cause life-threatening health problems.
A healthy immune system helps the body fight disease. It makes proteins called antibodies that identify and attack substances (called antigens) that enter the body and which might cause harm. The immune system of a person with APS misidentifies a substance that naturally occurs in our blood cells. It then makes antibodies that fight these “autoantigens” (antigens that are not from external sources). In other words, the body attacks itself. The main autoantigens associated with APS are phospholipids.
A phospholipid is a type of fat molecule that is the main building block of the outside layer of cell membranes. This is the case for bacteria and virus cells, but also in human cells.
Antiphospholipid antibody (aPL) describes antibodies that attack certain proteins that bind the phospholipid cell walls of blood cells located on the inner layer of the arteries or veins. These antibodies are generally detected by three tests, namely: lupus anticoagulant (LA), anticardiolipin antibody (aCL), and anti-Beta-2-glycoprotein-I antibody (aβ2GPI). All of these create enhanced risk for blood clotting.
The terminology used to discuss APS can be confusing. There is an important difference between the terms “antiphospholipid antibody” (aPL) and “antiphospholipid syndrome” (APS). A positive aPL test alone, even in high levels, does not necessarily mean that a person has APS. Adding to this confusion is that there are several aPL tests, as discussed further below.
No. There are many other causes of blood clots. Deep vein thrombosis (DVT), for example, can occur in anyone who is sedentary for long periods of time, such as during a long airplane flight or after surgery. There are also many non-APS conditions and genetic factors that can make a person more susceptible to forming clots, including some cancers and inherited mutations or protein deficiencies. People who use nicotine and/or who have a history of high blood pressure or high cholesterol are also at accelerated risk for clots.
Epidemiology studies range widely, with APS affecting anywhere between 0.001% to as many as 0.05% of people. About 10% of people who have no autoimmune disease may experience isolated or temporary, low-titer positive tests for antiphospholipid antibodies (aPL) without having APS. Persistent, high-titer aPL positivity is found in about 1% to 2% of people with no other systemic autoimmune diseases. Clinically significant aPL is much higher in people with other autoimmune diseases. About 20% to 30% of people with lupus, especially, have clinically significant aPL positivity for aPL. Clotting risk in these patients is higher but still low (less than 4% per year).
As with other systemic autoimmune diseases, it is not known exactly why the body makes these abnormal autoantibodies that cause APS. Researchers hypothesize that environmental factors, such as infections, trigger the production of these antibodies in the immune systems of people who may have some genetic predisposition. There is also evidence of a connection between having a gut microbiome that is unhealthy or less diverse than average and developing antiphospholipid syndrome.
No. Although doctors don’t yet understand how or why people get the antiphospholipid antibodies, we do know that they do not spread like an infection.
The primary symptoms of antiphospholipid syndrome are blood clots in the veins of the legs or arms, strokes (disruption of blood supply in part of the brain) and pregnancy problems such as miscarriage or pre-eclampsia. However, there are many other possible symptoms, including anemia or heart valve disease. On the other hand, some people whose bodies produce antiphospholipid antibodies (called being “aPL-positive”), develop no symptoms or APS-related health problems. Finally, other symptoms can appear as a result of the blood clots associated with APS, for instance leg swelling. Some people may have only one of these symptoms, while others have several of them. (See below for health problems associated with blood clots.)
Antiphospholipid syndrome can occur in otherwise healthy individuals, or in patients with other autoimmune disorders. 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").
Among people with no other systemic autoimmune disease, APS affects males and females about equally. Among APS patients who also have lupus, about 70% to 80% are women. This is largely because lupus itself affects women much more so than men. APS is more common among people with primarily White or Asian descent than in people with African descent.
Yes, APS that appears during childhood or adolescence is called pediatric antiphospholipid syndrome. A rarer form, known as neonatal antiphospholipid syndrome, is present at birth or develops within the first month after a baby is born and most often fades away after several weeks. Neonatal APS most often results from the passage of autoimmune antibodies from an aPL-positive mother to the child through the placenta. There have been cases, however, that were spontaneous.
Blood clots in the arteries or veins (sometimes on a microvascular level) caused by antiphospholipid antibodies can create a deep vein thrombosis (DVT) or pulmonary embolism as well as high blood pressure, heart attack, stroke, miscarriages, and many other problems. APS blood clot health complications include the following:
Doctors used to think so, but there now appears to be no correlation between APS and hardening of the arteries.
Yes, rarely. About 50% of people with APS have “primary APS.” They may experience blood clots and/or have pregnancy problems, and they are less likely to develop another autoimmune disease. Although 30% to 40% of lupus patients test positive for antiphospholipid antibodies, most people with both diseases develop them at the same time. In addition, some APS patients may develop lupus-like symptoms such as joint pain and fatigue, even if they do not have full lupus.
Women who have antiphospholipid syndrome are more likely to develop pregnancy complications, including miscarriages, preterm delivery (before 37 weeks), preeclampsia and eclampsia intrauterine growth restriction (reduced fetus size), and blood clots occurring while they are pregnant.
However, with appropriate monitoring and treatment, most women with APS can have successful pregnancies. Under current management of planned pregnancies, 80% of women with APS will deliver live newborn babies, and approximately 60% will have no pregnancy complications at all. (Learn more about APS and pregnancy or explore our relevant, ongoing clinical trials.)
Antiphospholipid syndrome is not currently believed to be directly inherited. However, it does seem to run in families. In a rare form known as neonatal APS, antiphospholipid antibodies may be passed through the placenta from mother to child. These antibodies in the infant tend to disappear within the first six months of life, and APS-caused blood clots in babies are extremely rare.
Antiphospholipid syndrome patients with other systemic autoimmune diseases are usually women; the female predominance is less obvious in primary APS patients. Antiphospholipid antibodies can be detected in approximately 15% of all stroke patients in the general population, 10% of heart attacks (myocardial infarction) and blood clots in large veins, and 9% of recurrent miscarriages.
There are no diagnostic criteria for APS. If a person has signs and symptoms that suggest they have APS, laboratory tests are ordered to determine the presence of antiphospholipid antibody (aPL). A conclusive diagnosis requires positive results from at least two such blood tests, spaced three or more months apart.
Because many symptoms of APS, including miscarriages, may be caused by other, more common conditions, many patients go undiagnosed for years. Adding to this confusion, people with APS sometimes receive a false-positive test result for syphilis, a sexually transmitted disease. On the other hand, there is also a problem with overdiagnosis: Some people are incorrectly diagnosed with APS, based solely on a single positive test for (aPL), which can occur frequently in healthy people. (Learn more by reading Classification Versus Diagnosis of Antiphospholipid Syndrome: How Are They Different?).
There are three blood tests which can confirm a diagnosis of APS if strongly positive results are consistent when two or more tests are performed at least 12 weeks apart:
About 10% of people who have no autoimmune disease may experience isolated or temporary, low-titer positive tests for antiphospholipid antibodies (aPL) without having APS. Persistent LA and/or high-titer aCL/aβ2GPI positivity is found in about 1% to 2% of people with no other systemic autoimmune diseases. This is considered “clinically significant”, meaning that a person may have APS. Clinically significant aPL is much higher in people with other autoimmune diseases. About 30% to 40% of people with lupus, especially, have clinically significant positivity for antiphospholipid antibodies. Clotting risk in these patients is higher but still low (less than 4% per year).
The primary specialist a person with APS should see depends on the symptoms with which they present. For example, hematologist may be consulted after a deep vein thrombosis, neurologist after stroke, or an obstetrician after a miscarriage. Because many people with APS also have other systemic autoimmune diseases (such as lupus), a rheumatologist may be consulted to help manage care. Patients should encourage continual dialogue between their primary care physician (family doctor) and any APS specialists they consult.
Even among specialist physicians such as hematologists or rheumatologists, only some actively manage antiphospholipid syndrome, while others may focus on other diseases. For this reason, it can be challenging to find appropriate APS specialists in some areas. (Find a doctor at HSS who treats APS, or search your area if you live outside the greater New York City region.)
Anyone positive for antiphospholipid antibodies who experiences a blood clot, has a stroke, or who is pregnant or planning to become pregnant should consult a physician with expertise in APS as soon as possible. Given that APS is a systemic autoimmune disease, a rheumatologist is generally involved in the care of APS patients. However, depending on on which organ (or organs) are involved, other specialists also provide care to APS patients. For example, if blood clots are your only symptom, a hematologist experienced in APS can provide care.
Besides blood clots, some other indicators to see an APS specialist include having low platelet counts, certain types of anemia, heart valve disease, skin rash called livedo, and a false-positive syphilis test. Lastly, if you are aPL-positive and need to have surgery, you should consider including an APS specialist on your healthcare team as APS patients are at increased risk for blood clots when they undergo surgeries. Learn more about special precautions aPL-positive patients should take when having surgery.
APS patients with a history of blood clots are usually placed on a long-term plan of anticoagulant medications (commonly called “blood thinners”), such as aspirin, warfarin, or heparin. Other medications are used to treat a subgroup of APS patients. These include:
For all people patients who are positive for antiphospholipid antibodies, regardless of whether they have had clot, it is essential to eliminate as many reversible risk factors as possible, such as using nicotine, taking oral contraceptive pills or hormone replacement therapy. Patients who have unrelated cardiovascular diseases such as high blood pressure or diabetes must take care to manage these conditions to reduce their risk for clots.
Any person who has had multiple blood clots due to APS will likely need to take anticoagulation medications for life in order to manage the disease. The need for permanent treatment will depend on each individual and their circumstances. Some people are positive for antiphospholipid antibodies but who have had no symptoms may not require treatment but should be monitored.
HSS is one of the leading medical centers in the United States for treating adults and children who have antiphospholipid syndrome. Clinicians in our Lupus and APS Center of Excellence provide the highest quality of care to enhance our patients’ lives, and our top APS physician researcher serves as a medical advisor to the APS Foundation of America. HSS is also a founding member of the APS ACTION International Clinical Database and Repository, an international body of clinician researchers dedicated to advancing the understanding and management of APS.
Get a deep dive on antiphospholipid syndrome topics from the articles below.
Read about the different treatment options available to antiphospholipid-antibody-positive (aPL+) patients.
These articles discuss the top 10 points lupus and APS patients should know about various topics related to their conditions.