The Treatment of Lupus in Pregnancy

by Mr Roy G. Farquharson MD FRCOG

Consultant in Obstetrics and Gynaecology Miscarriage Clinic, Liverpool Women's Hospital

In recent years, Obstetricians have realised the importance of a newly found part of the lupus disease spectrum. This new condition, called antiphospholipid antibody syndrome (APS), (see Hughes' Syndrome), is known to cause recurring miscarriage and thrombosis in the maternal circulation. The patient, therefore, comes to the attention of the Obstetrician because of recurring pregnancy loss, usually associated with death of the unborn baby (fetus) at a late gestation (between 10 and 24 weeks of pregnancy). For the Obstetrician, therefore, the treatment of lupus in pregnancy has taken on a new dimension and, as such. many different treatments have been tried in an attempt to overcome this significant problem.

At Liverpool Women's Hospital, we run a Miscarriage Clinic dedicated to those women who have suffered recurring pregnancy loss. We have over 200 individual women who have the antiphospholipid syndrome as a cause, approximately 20% of our total Miscarriage Clinic population. Of these 200, approximately 5%-10% have SLE, similarly, 5%-10% of an SLE female population will have the antiphospholipid syndrome. These woman arrive at the clinic having lost confidence in their reproductive ability and are often completely puzzled about the cause of their recurring miscarriage. An information leaflet has been developed to try and provide some educational background to their problem. It is very important at this stage for lupus patients, before pregnancy, to gain as much information and to ask as many questions about their condition as possible.

The treatment of APS and lupus in pregnancy has gone through several phases in recent years. In the 1980's, high dose steroids and low dose aspirin were the mainstay of therapy. However, the disadvantage of high dose steroids soon became evident. The main complications were of bone loss (osteoporosis) causing vertebral compression and collapse in the maternal lumbar spine. In addition, the steroids made the pregnant woman susceptible to infection by bacteria that could affect the mother, but, just as importantly, may kill the baby, such as listeriosis. For these reasons, alternative therapy was sought and the most up-to-date therapy is the use of low dose aspirin combined with low molecular weight heparin as a daily injection.

Lose dose aspirin 75 mg daily works by preserving prostacyclin synthesis from platelets, providing unsticky platelets and opening of the vessels, while inhibiting thromboxane synthesis, which tends to make platelets stick together and blood vessels constrict and narrow, promoting thrombosis. Lose dose aspirin alone can provide up to 70%-80% chance of success, where the patient has only one parameter positive for the antiphospholipid syndrome (Granger et al., Lupus, 1997). In the presence of 2 parameters positive for APS, for instance lupus anticoagulant and anticardiolipin antibody, then the pregnancy failure rate rises to approximately 50%. It is these patients who benefit from the combination of low dose aspirin and a new product called low molecular weight heparin which is safe in pregnancy. This is given as a daily injection under the skin. Heparin works by direct effect on the coagulation cascade and provides good anticoagulation. The side effects of low molecular weight heparin are few and, in particular, there is little risk of haemorrhage (approximately 1% develop low platelet counts). Bone loss studies in pregnant women show an average bone loss of 4% due to pregnancy. When heparin is added a further 2% loss is recorded, making the total 6% on average, using low molecular wight heparin for approximately 28 weeks during pregnancy. the good news is that all these women recovered their bone loss within 18 months after pregnancy.

At the present time, low dose aspirin and low molecular weight heparin give a very good treatment for APS in pregnancy, providing a good chance of a successful pregnancy, while protecting the mother against the ravages of thrombosis, eg transient ischaemic attacks (TIAs) or venous thrombo-embolic disease (VTD). Further research is always needed and, at the present time, a multicentre trial, comparing aspirin versus aspirin and heparin in pregnancy, is underway and, hopefully, the results will be ready by the end of next year.