Antiphospholipid Syndrome (APS)

What happens in APS

Antiphospholipid antibodies target proteins that bind to phospholipids, the fats that make up cell membranes. These antibodies activate the cells that line blood vessels, platelets and the clotting system, tipping the balance toward clot formation. In the placenta, they interfere with blood flow and the development of placental tissue, causing pregnancy complications.

APS can be:

• Primary APS: occurring on its own
• Secondary (associated) APS: occurring with another autoimmune disease, most often systemic lupus erythematosus
• Catastrophic APS: a rare, life-threatening form with clots in many small vessels and multiple organ failure over days

Symptoms

Blood clots

• Deep vein thrombosis: a swollen, painful, warm leg; the most common clotting event in APS
• Pulmonary embolism: sudden breathlessness, chest pain, rapid heartbeat
• Stroke and TIA: APS is an important cause of stroke in people under 50
• Heart attack, clots in kidney, liver or eye blood vessels
• Clots in unusual sites such as abdominal veins

Pregnancy complications

• three or more consecutive early miscarriages (before 10 weeks)
• one or more unexplained loss of a normal-appearing fetus after 10 weeks
• premature birth before 34 weeks due to severe preeclampsia or placental insufficiency
• poor fetal growth

Other features

• livedo reticularis: a lacy, mottled purple pattern on the legs and arms
• low platelet count (thrombocytopenia)
• heart valve thickening
• migraine-like headaches, memory problems
• kidney damage from small clots
• skin ulcers

Who gets APS

APS is about five times more common in women than men and usually diagnosed between ages 30 and 50. Antiphospholipid antibodies are found in 1 to 5% of healthy people, mostly at low levels without causing problems. They are present in about 30 to 40% of people with lupus. Smoking, estrogen-containing contraceptives, pregnancy, surgery and immobility increase clotting risk in people with the antibodies.

Diagnosis

Diagnosis requires a clinical event (clot or pregnancy complication) plus persistently positive laboratory tests:

• Lupus anticoagulant: a clotting test (despite its name, it promotes clotting in the body)
• Anticardiolipin antibodies (IgG or IgM) at moderate to high levels
• Anti-beta-2 glycoprotein I antibodies

Tests must be positive on two occasions at least 12 weeks apart, because antibodies can appear temporarily after infections. Having all three positive ("triple positive") carries the highest clotting risk. Lupus anticoagulant testing is affected by anticoagulant medicines, so timing is planned carefully.

Other tests include a full blood count, kidney function, lupus antibodies (ANA, anti-dsDNA) and imaging of clots.

Treatment

After a venous clot

Long-term anticoagulation with warfarin, usually aiming for an INR of 2 to 3. Direct oral anticoagulants (such as rivaroxaban or apixaban) are not recommended for people with high-risk APS, especially triple-positive patients or those with arterial clots, because studies showed more clots than with warfarin.

After an arterial clot

Warfarin, sometimes at a higher intensity or with aspirin, guided by a specialist.

Antibodies without clots

Low-dose aspirin may be advised for people with high-risk antibody profiles, particularly with lupus. Avoiding smoking and estrogen-containing contraception, and using clot prevention during surgery or long flights, are important.

Pregnancy

• Low-dose aspirin started before or early in pregnancy.
• Low molecular weight heparin injections throughout pregnancy and for 6 weeks after birth for women with obstetric APS or previous clots.
• Warfarin is avoided in pregnancy because it can harm the baby; women on warfarin switch to heparin before 6 weeks of pregnancy.
• Close monitoring of blood pressure, fetal growth and placental blood flow.

With treatment, most women with APS have successful pregnancies.

Catastrophic APS

Treated in intensive care with anticoagulation, high-dose steroids, plasma exchange and/or IV immunoglobulin.

Living with APS

• take anticoagulants as prescribed and attend INR checks
• learn the signs of clots and bleeding
• avoid smoking and estrogen-containing contraceptives and HRT
• plan pregnancies with your specialist
• tell every doctor and dentist you have APS and take blood thinners
• stay active and move regularly on long journeys

Frequently asked questions

What are the symptoms of antiphospholipid syndrome?

The main features are blood clots, such as a swollen painful leg (DVT), breathlessness from a lung clot, or a stroke at a young age, and pregnancy problems such as recurrent miscarriage, stillbirth or severe preeclampsia. A lacy purple skin pattern and low platelets are other clues.

How is APS diagnosed?

APS is diagnosed when someone has had a clot or pregnancy complication and tests positive for lupus anticoagulant, anticardiolipin or anti-beta-2 glycoprotein I antibodies on two occasions at least 12 weeks apart. Repeat testing excludes temporary antibodies caused by infection.

Can you have a healthy pregnancy with APS?

Yes. With low-dose aspirin, heparin injections and close monitoring, most women with APS have successful pregnancies. Planning before conception with a specialist and switching from warfarin to heparin early are important.

Is antiphospholipid syndrome the same as lupus?

No. APS can occur on its own (primary APS) or alongside lupus. Many people with lupus have antiphospholipid antibodies, and some develop APS. People with APS are monitored for signs of lupus, but most with primary APS never develop it.

Why is warfarin preferred over newer blood thinners in APS?

Studies found that direct oral anticoagulants such as rivaroxaban led to more clots, especially arterial clots, in high-risk APS than warfarin. Guidelines therefore recommend warfarin for most people with APS, particularly those who are triple-positive or have had arterial clots.