Antiphospholipid Syndrome (APS)

This site is intended for healthcare professionals as a useful source of information on the diagnosis, treatment and support of patients with lupus and related connective tissue diseases.
APS is a disorder of coagulation which can be a primary diagnosis or secondary to lupus. The syndrome is characterised by ‘sticky blood’ where major features noted include recurrent thrombosis both in veins and arteries, thrombosis including potentially serious organ disease such as cerebro-vascular accidents (CVAs) and a whole variety of other symptoms (see table below). For women with this syndrome in pregnancy there is a high risk of recurrent miscarriage due to thrombosis of small vessels leading to the baby via the placenta. Rarely antiphospholipid syndrome can lead to generalised thrombosis with a high risk of death, termed ‘catastrophic antiphospholipid syndrome’.
Vein thrombosis



Arterial thrombosis

Pregnancy loss

Other features



Blood tests
Arm vein thrombosis
Kidney vein thrombosis
Thrombosis in eye veins and veins of the brain

Leg artery clots/heart attacks etc.

Recurrent miscarriages due to placental thrombosis

Low platelets (occasionally)
Livedo (blotchy skin rash)
Migraine

Antiphospholipid Antibodies - Lupus anticoagulant and anticardiolipin antibodies
The hallmark of a syndrome is the presence of antibodies in the blood known as antiphospholipid antibodies. These are antibodies which can be detected in any hospital and have now become standard in the testing of lupus patients. The antibodies are extremely closely involved with the risk of thrombosis though how and why they cause thrombosis is still not understood. They are directed against phospholipid, the membranes of cells (as well as the membranes of platelets) and have been shown to affect clotting properties as well as blood flow properties.

There is a slight genetic tendency to develop APS, as in lupus. Auto-immune in origin (like lupus), it occurs as a result of the immune system producing abnormal antibodies. While APS can be regarded as a variant of lupus it is probable that in the vast majority of cases the syndrome remains ‘pure’ and rarely develops into more classical symptoms of lupus.

Clinical features of APS

The brain is frequently involved in this syndrome. The most dramatic presentation is stroke. It is now recognised that the antiphospholipid syndrome is an important world-wide cause of strokes, estimated to be responsible for strokes in up to 20% of individuals under the age of 40. The discovery of the syndrome has proved a major incentive to the study of strokes in general. Stroke may be sudden and dramatic or it may be gradual, presenting as transient ischaemic attacks (TIAs), where the patient reports severe headaches, slurring of speech with weakness in an arm and leg. Frightening to the patient and clearly of vital importance, they need urgent investigation (including brain scanning) and treatment, usually with anticoagulants such as warfarin.

We now recognise that in many more patients, subtle brain disease is present and in some patients a history of gradual memory loss, of occasional use of wrong words or speaking antedates the diagnosis by months or even years. One of the most dramatic features of patients with this form of illness is the improvement which occurs on anticoagulants and conversely the return to slurred speech which occurs if anticoagulation is ineffective or has to be stopped.

Other neurological features

Migraine is frequent and often precedes the diagnosis by many years; it is not uncommon for patients to have a history of severe migraine as a teenager. Very rarely, movement disorders such as chorea (St Vitus Dance) are a manifestation of the disease. If the parts of the brain affecting the eye or the nerve tracts to the eye are affected then visual symptoms may occur and very rarely visual loss has developed. If the spinal cord is involved then weakness in the legs is a feature.

Heart

Thrombosis in the coronary arteries produces chest pain and may even produce a classical heart attack. It is now recognised that antiphospholipid syndrome is an important cause of coronary artery disease which is potentially preventable. Occasionally the valves of the heart are affected in this syndrome, sometimes in a subtle way (heart murmurs) but occasionally more dramatically with shortness of breath and abnormalities shown on echo-cardiography.

Other organs

Thrombosis may affect any organ including the liver, spleen, kidneys and the adrenal glands each given medical problems associated with the disease of those organs. A rare manifestation is thrombosis in arteries that supply the joints, especially the hip joint, and collapse of the hip (possibly avascular necrosis) has been seen in small numbers of APS patients.

Thrombocytopenia

A normal platelet count ranges from 150,000 to 450,000 platelets per micro litre of blood. This can lead to an increased risk for bruising, purpura in the forearms, petechia (pinpoint haemorrhages) on skin and mucous membranes, nosebleeds and/or bleeding gums.

Both anticardioplin antibodies and the lupus anticoagulant react against proteins that bind to a complex molecule of phospholipid and protein. It is clear that the other previously well known risk factors for clotting such as the contraceptive pill, HRT and smoking, all increase the chances of thrombosis. The exact cause is not known although it is known to be a coagulation activation that is associated with thrombosis and vascular disease.

Treatment

Treatment is with anticoagulants. For those patients with less serious problems such as headaches, a daily low-dose of aspirin 75mg is usually advised. For those who carry the antiphospholipid antibodies but have never had a thrombosis, a pragmatic decision to treat with low-dose aspirin is often made as the benefits outweigh the potential risks of a thrombotic event. For those who have had a major thrombosis, especially a CVA, life-long warfarin is commenced with the anticoagulation range within an INR of 2.0 – 3.0. The gains from diagnosing and treating this condition are so huge; the dangers of missing the disease or not treating it are great.

Provided that the diagnosis is made and the treatment with anticoagulation is precise, patients do very well indeed without further thrombosis. As has been mentioned the major impact this discovery has had has been in both the fields of neurology and obstetrics where women who had previously had multiple miscarriages for ‘unknown reasons’ now have successful pregnancies.