APS is a separate condition to Lupus, a disorder of coagulation which can occur with or without lupus or other auto-immune conditions. The syndrome is characterised by ‘sticky blood’ where major features noted include recurrent thrombosis, potentially in both veins and arteries, including potentially serious organ disease such as stroke 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 widespread generalised thrombosis which has high risk of death, termed ‘catastrophic antiphospholipid syndrome’.

The hallmark of the syndrome is the presence of antibodies in the blood known as anti-phospholipid antibodies, which are now standard tests for patients with lupus. The antibodies are extremely closely involved with the risk of thrombosis though still not fully understood. The antibodies are directed against phospholipid, in the membranes of cells (including membranes of platelets) and have been shown to affect clotting as well as flow in blood.

Clinical features of APS

As APS affects the blood, 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 cause of stroke internationally, estimated to be responsible for up to 20% of cases in individuals under the age of 40. The discovery of the syndrome has proved a major incentive to study stroke. Stroke or TIA (transient ischaemic attack) is often sudden and dramatic (facial drooping, arm weakness and numbness, speech difficulty). These symptoms are usually (but not always) frightening to the patient and of vital importance; they need urgent investigation (including brain scanning). Time is of the essence and this really is worth reminding patients they should call for an ambulance to get paramedic attention rapidly. Treatment for thrombosis is with lifelong treatment with anticoagulants, such as warfarin.

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

Other neurological features

Migraine is frequent in APS and can precede the diagnosis by many years; it is not uncommon for patients to have a history of severe migraine as a teenager. Depending on which blood and nerve supplies are affected, different areas of the body can be affected too. If the parts of the brain affecting the eye are affected then visual symptoms may occur and very rarely visual loss may have developed. If the spinal cord is involved then weakness and numbness in the legs can be a feature (transverse myelitis).

Heart

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-cardiograph. Thrombosis in the coronary arteries produces chest pain that may result in a classical heart attack even aged less than 40 years.

Other organs

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

Thrombocytopenia

A normal healthy platelet count ranges from 150-450 platelets x 10*9 per litre of blood. Due to platelets role in clotting, a low out of range count can lead to an increased risk of bruising, purpura in the forearms, petechia (pinpoint haemorrhages) on skin and mucous membranes, nosebleeds and/or bleeding gums (usually if less than 50 x 10*9/L). Platelet counts in APS are often 70-100 x 10*9/L without any signs or symptoms but there can still be a risk of clotting, not bleeding.

Both anti-cardiolipin antibodies and the lupus anticoagulant react against proteins that bind to a complex molecule of phospholipid and protein. Other well known risk factors for clotting such as the contraceptive pill, HRT and smoking also 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 based on thinning the blood within a tightly controlled range, with anticoagulants. For those patients with less serious problems such as headaches, a daily low-dose of aspirin 75mg may be advised. For those who carry the antiphospholipid antibodies but have never had a thrombosis, a pragmatic decision to treat with low-dose aspirin may be made if the benefits outweigh the potential risks.

For those who have had a thrombosis, especially a myocardial infarction or coronary vascular accident (MI or CVA), life-long anticoagulation is commenced, usually with warfarin, to maintain an anticoagulation range within an INR of 2.0 - 3.0 although sometimes increased to 3.0 - 4.0. Recent advances with novel oral anti-coagulants (NOACs, or DOACs - direct oral anticoagulation) such as
rivaroxaban are not recommended for those with APS.

The gains from diagnosing and treating this condition are so huge; the dangers of missing the disease or not treating it can be catastrophic. Provided that the diagnosis is made and the treatment with anticoagulation is precise and well monitored, most patients do very well without further thrombosis. The major impact of this discovery has been in both neurology and obstetrics, and women who previously had multiple miscarriages, now have successful pregnancies.