Antiphospholipid Syndrome



Last Review Date: June 14, 2019


What is antiphospholipid syndrome?

Antiphospholipid syndrome (APS) is an autoimmune disorder and a hypercoagulable disorder. It is associated with the production of one or more antiphospholipid antibodies. These are autoantibodies that target the lipid-proteins found in the outermost layer of cells (cell membranes) and platelets. The autoantibodies interfere with the blood clotting process in a way that is not fully understood. APS is also associated with thrombotic episodesthrombocytopenia and with pregnancy complications such as pre-eclampsia and recurrent miscarriages. There is now good evidence to suggest the effects on the placenta are different from the effects on blood vessels and inflammation.

The main antiphospholipid antibodies associated with APS include lupus anticoagulantcardiolipin antibody and beta-2 glycoprotein 1 (β2GP1) antibody. These antibodies increase an affected person's risk of developing recurrent inappropriate blood clots in both veins and arteries. Those with APS may experience a single thrombotic episode or have multiple occurrences. Symptoms and complications may range from mild to critical. Blood clots that form 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 embolismheart attackstroke 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 (viscera), referred to as catastrophic APS.

Those with antiphospholipid antibodies may have APS and another co-existing autoimmune disorder such as systemic lupus erythematosus (SLE) or may have one or more of the antibodies present with no associated symptoms. Antiphospholipid antibodies may be seen in those with HIV, some cancers, in the elderly and temporarily, with infections (e.g. Q fever) and with drugs such as phenothiazines and procainamide. They may also be found in 1 per cent to 5 per cent of healthy people.

Antiphospholipid syndrome may affect anyone but is most frequently seen in women of child-bearing age and in those with another autoimmune disorder. According to the March of Dimes, APS is the most common acquired thrombophilia, affecting up to 5 per cent of pregnant women.


Signs and Symptoms

The symptoms associated with APS will vary from person to person and with each thrombotic episode. With pregnant women, APS may cause recurrent miscarriages, pre-eclampsia and premature births but no distinguishable symptoms. Symptoms associated with a blood clot depend on where the clot forms in the body and the damage that occurs. APS signs and symptoms may include:

  • Persistent headaches
  • Chest pain
  • Shortness of breath
  • Nausea
  • Speech and/or cognitive changes
  • Seizures
  • 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)

Tests

The aims 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 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 arterial, venous, or small-vessel blood clot occurring in any tissue or organ

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-eclampsiaeclampsia, 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 must be present on two 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:

Other tests that may be ordered include:

  • Activated partial thromboplastin time (APTT, to evaluate blood clotting)
  • Full blood count (FBC, to evaluate blood cells and platelets)
  • A variety of additional tests to evaluate other causes for a person's symptoms, such as 1:1 Mix study (dilute APTT) to detect lupus anticoagulant activity

Non-Laboratory Tests

Imaging scans may be performed to confirm a thrombotic episode, to locate a blood clot, evaluate organ damage, and to monitor a fetus. These may include:

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

For more on these, see the web sites Inside Radiology (Australia) and Radiologyinfo.org (US).


Treatment

There is no cure for antiphospholipid syndrome. 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.

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

Anticoagulants such as warfarin and heparin are typically used to treat existing blood clots. To prevent recurrence, long-term anticoagulation with warfarin or low-dose aspirin is often necessary.

Women with APS can have successful pregnancies but they and their unborn baby must be carefully monitored. Warfarin cannot be used in pregnancy as it harms the developing baby. Many people may be given heparin injections beneath the skin (subcutaneous) and low-dose aspirin during pregnancy to help minimise the potential for fetal loss.

For patients with catastrophic APS, a combination of anticoagulant, glucocorticoid and plasma exchange treatment with or without intravenous immune globulin is required. Cyclophosphamide and rituximab have been used in addition.

Additional treatments may be required to address thrombocytopenia and other APS complications.


Related Pages

On This Site

Tests: Antiphospholipid AntibodiesLupus Anticoagulant TestingCardiolipin AntibodiesBeta-2 Glycoprotein 1 AntibodiesFull Blood CountPlatelet Count
Conditions: Autoimmune DisordersSystemic Lupus ErythematosusExcessive Clotting DisordersHeart AttackStrokePregnancy

Elsewhere On The Web
Heathdirect Australia – antiphospholipid syndrome

National Human Genome Research Institute: Learning About Antiphospholipid Syndrome (APS) (USA)
National Heart Lung and Blood Institute: What Is Antiphospholipid Antibody Syndrome? (USA) 
American College of Rheumatology: Pregnancy and Rheumatic Disease (USA)
March of Dimes Pregnancy Complications: Thrombophilias (USA)
APS Foundation of America, Inc (USA)
Lupus Foundation of America, Inc.: Antiphospholipid Antibodies (USA)
American Society of Hematology: Blood Clotting & Pregnancy (USA)