LUPUS: A Guide for Nurses
In 1983 a syndrome characterised by "sticky blood" was described in detail by the research team at St Thomas' Hospital, London. The major features were of recurrent thrombosis both in veins (for example leg vein thrombosis on the "pill") and arteries, thrombosis including potentially serious organ disease such as the brain (strokes) and a whole variety of other symptoms (see table). For women with this syndrome in pregnancy there is a high risk of recurrent miscarriage probably due to thrombosis of small vessels leading to the baby via the placenta.
| 1. Vein thrombosis (e.g. leg vein thrombosis on the pill) |
Arm vein thrombosis Kidney vein thrombosis Thrombosis in eye veins and veins of the brain. |
| 2. Arterial thrombosis | Leg artery clots/heart attacks etc. |
| 3. Pregnancy loss | Recurrent miscarriages due to placental thrombosis |
| 4. Other features | Low platelets (occasionally) Livedo (blotchy skin rash) Migraine |
| 5. Blood tests | Antiphospholipid 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.
In most laboratories two tests are asked for; "anticardiolipin antibodies" and the confusingly named "lupus anticoagulant". The latter term is a historical one as it was first thought to be associated not with clotting but with bleeding. This has now been proved to be wrong and in fact the term should be discarded. There is a considerable overlap between the two tests but as a small number of patients are positive for only one or the other it is recommended that both are carried out on the blood.
The brain is frequently involved in this syndrome. The most dramatic presentation is stroke. It is now recognised that the Hughes 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, the patient noticing headaches, slurring of speech, weakness in an arm (so called "transient ischaemic attacks" "TIAS"). 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 "gobbledygook" 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 etc which occurs if anticoagulation somehow goes wrong.
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 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.
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.
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 ("avascular necrosis") has been seen in small numbers of APS patients.
The normal platelet count is 150,000 or more. Many patients with Hughes syndrome run platelet counts around 100,000 mark. If the platelet count falls, e.g. down to below 40,000 or 30,000 bruising and even bleeding problems can occur.
The problems associated with pregnancy, notably recurrent miscarriage, are described in detail in 'Lupus and Pregnancy'.
The antibodies are directed against a complex molecule of phospholipid and protein. The mechanisms whereby these antibodies finally result in thrombosis are very uncertain and an enormous amount of research is going on in this particular area. It is clear that the other previously well known risk factors for clotting i.e. the contraceptive pill and smoking both increase the chances of thrombosis.
There is a slight genetic tendency, as in lupus. The disease is an "autoimmune disease" (like lupus) in that the immune system appears to produce 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 does not go on later to become more classical systemic lupus.
Treatment is with anticoagulants. For those patients with less serious problems such as headaches, a daily dose of aspirin (75mg junior aspirin) is usually advised. For those individuals in whom the antibody levels have been found to be positive but who have never had thrombosis there is still disagreement about the best form of therapy. It might be argued that these individuals do not require any treatment although, increasingly, doctors are suggesting that there is so little harm in taking one junior aspirin daily and so much potentially to be gained that treatment is worthwhile. For those with major thrombosis, especially strokes, the anticoagulation should be with an INR of 3 - in plain English this means that the blood should be three times "as thin" as normal blood. For these patients anticoagulation should probably be lifelong. 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.