Antiphospholipid Syndrome

Also Known As

APS

APLS

Antiphospholipid Antibody Syndrome

Hughes Syndrome

Anticardiolipin Antibody Syndrome

aCL Syndrome

aPL Syndrome

Lupus Anticoagulant Syndrome

"Sticky Blood Syndrome"

This article was last reviewed on

31 October 2014.

This article waslast modified on 16 August 2021.

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 lupus anticoagulant, cardiolipin antibody, and beta-2 glycoprotein I (β2GP1) antibody. Cardiolipin and B2GP1 may be IgG or IgM antibodies. These antibodies increase an affected person's risk of developing recurrent inappropriate blood clots in both veins and arteries. Individuals with APS may experience one or more thrombotic episodes. 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 they 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.

Individuals with antiphospholipid antibodies may have APS and another co-existing autoimmune disorder such as lupus (systemic lupus erythematosus or SLE) 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 are often detected and temporarily during infections and with some medications, such as the psychiatric drugs phenothiazines or the antibiotic amoxicillin and the heart rhythm regulator procainamide.

Antiphospholipid syndrome may affect anyone, but women of child-bearing age or those with another autoimmune disorder are more commonly affected. Having a family member with antiphospholipid syndrome may increase a person's risk.

Antiphospholipid antibodies are found in 1% to 5% of young, healthy people and up to 10% of the general public. According to the March of Dimes, APS is the most common acquired excessive clotting disorder, affecting up to 5% of pregnant women.

About Antiphospholipid Syndrome

Signs and Symptoms
The symptoms associated with APS will vary from person to person and with each episode of inappropriate blood clot formation (thrombotic episode).

Pregnant women with APS may have recurrent miscarriages, pre-eclampsia, or premature births but with no distinguishable symptoms.

Symptoms associated with a blood clot depend upon where the clot forms in the body and damage that occurs. Blood clots may form in the veins of the legs (deep vein thrombosis) and may travel to the lungs (pulmonary embolism). Blood clots can also form in arms or leg arteries (peripheral arterial thrombosis), for example. Risk of developing blood clots can increase with pregnancy, immobility, surgery, smoking, oral contraceptives, or high cholesterol.

Examples of APS signs and symptoms include:

Persistent headaches

Stroke

Repeated miscarriages or other pregnancy complications such as pre-eclampsia

Chest pain

Shortness of breath

Nausea

Speech and/or cognitive changes

Seizures

Memory loss

Redness, swelling, and pain in a leg or arm

A red lacy rash on the arms or legs (livedo reticularis)

Skin ulcers

Mild to severe bleeding (with significant thrombocytopenia, a condition in which the body has a lower than normal amount of platelets, or with concomitant antibodies that target one of the coagulation factors, such as Factor X; people with this condition may have few or no other symptoms.)

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 foetus 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 and less than 5 years from clinical symptoms: Lupus anticoagulant: present, according to the guidelines of the International Society on Thrombosis and Hemostasis Anticardiolipin antibody: present at a medium or high level(>40 MPL or GPL or greater than the 99th percentile for normal) 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)
Full blood count (FBC), 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 foetus. These may include:

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

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 minimise tissue and organ damage. Those who have antiphospholipid antibodies but have never had a thrombotic episode or miscarriage are not typically treated. They may never be diagnosed with APS or have associated symptoms or complications.

Individuals with APS should minimise 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 recurrence, long-term or indefinite anticoagulation with warfarin or an alternative anticoagulant is often necessary. Aspirin may be used if someone has risks for heart attacks.

Women with APS can have successful pregnancies, but they and their unborn baby must be carefully monitored. 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.