Dr. J. Ginsberg, Professor of Medicine McMaster University, Director of the
Thromboembolism Clinic, Hamilton Health Sciences Corporation, McMaster Site.

Antiphospholipid Antibodies and Pregnancy Problems
Jeffrey S Ginsberg, MD, FRCPC

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects thousands of Canadians, primarily women of child bearing potential. Patients with SLE have a variety of different antibodies that circulate in the blood. Antibodies are proteins that are directed against (and often neutralize) other substances called antigens. Some of these antibodies are directed against normal constituents of the body and this can lead to several of the clinical manifestations that occur in patients with SLE.

Antiphospholipid antibodies are a group of antibodies that can be detected as "lupus anticoagulants" or "anticardiolipin antibodies". Lupus anticoagulants and anticardiolipin antibodies are grouped together, are detected using different laboratory techniques. Some patients can have both (70%), whereas some (30%) patients have one without the other. It is not clear whether lupus anticoagulant or anticardiolipin antibodies are more strongly associated with clinical complications (see below), nor is it clear whether the of both is associated with a higher risk of problems. The term, lupus anticoagulant, is confusing these antibodies can occur in people without lupus and, 2) although they act as "anticoagulant" in the test they are in fact "pro-coagulant" in the body; that is, they are associated with a tendency for clotting problems. addition, women who have the persistent presence of antiphospholipid antibodies tend to run into pregnancy problems, particularly miscarriages. Although the evidence is mounting that there is an association between these antibodies and clots and pregnancy problems, we have no idea about the mechanism and, indeed, whether these antibodies are "cause and effect". There are many theories about possible mechanisms whereby these antibodies produce clinical problems, but none is proven. One of the peculiar characteristics of antiphospholipid antibodies is the fact that they can come and go in an entirely unpredictable fashion. Therefore, it is not unusual for us to test a patient at one point in time and detect a lupus anticoagulant and three months later, the lupus anticoagulant has disappeared. It is likely that patients who have persistent presence of these antibodies with multiple tests (there are several tests that are used to detect lupus anticoagulant) are more prone to clinical complications than patients who have transient positivity or persistent negativity; these clinical complications include clotting problems and miscarriages.

In a recent study that was performed at McMaster University, with assistance from the Lupus Society of Hamilton, we were able to demonstrate that the persistent presence of lupus anticoagulant-positivity and/or anticardiolipin antibody-positivity was associated with an increased risk of previous pregnancy loss. Moreover, of the seven women (of a total of 42) who had had multiple pregnancy losses, all had lupus anticoagulant and four of these also had anticardiolipin antibodies. The good news is that of the 42 patients, 24 had had many pregnancies with no problems. Therefore, although these antibodies are associated with an increased risk of previous pregnancy problems, their presence does not mean that the likelihood of a favourable outcome is unacceptably low. In addition, future clinical trials should be performed to determine whether the presence of antiphospholipid antibodies in SLE patients is predictive of future pregnancy problems.

There are several approaches that have been used to prevent pregnancy problems in pregnant lupus patients with antiphospholipid antibodies. We must also be concerned about clotting problems in pregnant women with antiphospholipid antibodies since, in general, pregnancy is a high risk period for clots. Therapies that have been evaluated include aspirin alone, aspirin plus prednisone, aspirin plus heparin (an injectable type of blood thinner) and heparin alone. To date, no large clinical trials have performed to provide us with firm guidelines and so the pattern of practice varies in different centres.

Dr Carl Laskin and his collaborators in Toronto have recently completed a double blind randomized trial aspirin plus prednisone versus placebo in the prevention of recurrent pregnancy loss in women with prior pregnancy losses. Included in this study were patients with antiphospholipid antibodies. As of August the final analysis has yet to be performed. However, this excellent study has the potential to influence clinical practice profoundly. It is our intention at McMaster University, to collaborate in multi-centre studies headed-up by Dr Laskin that will ultimately improve outcomes in pregnant patients with SLE and antiphospholipid antibodies. The results of these future trials will provide physicians and patients with practice guidelines and optimize outcomes for such women.

Articles

Home