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Writing and Publishing Scientific Articles
Example of an Introduction Needing Improvement (Clinical Study)
In 1983, Harris et al linked the presence of anticardiolipin antibodies with a syndrome of spontaneous thrombosis and fetal death. 1 Despite the many reports since then, the best treatment for the so-called antiphospholipid syndrome remains unknown. This is partly because the syndrome is complex. In fact, there are 2 syndromes, primary (no association with other diseases) and secondary (associated with lupus erythematosus or other rheumatic diseases). Up to one third of patients with lupus erythematosus have antiphospholipid antibodies. 2 The name of the syndrome is problematic. Negatively charged phospholipids, such as cardiolipin, were originally considered the most important autoantigens in the syndrome. However, β 2 -glycoprotein I, also known as apoliprotein H, has been shown to be more important. 3 β 2 -Glycoprotein I binds cardiolipin and other anionic phospholipids and helps dispose of apoptotic cells. The former function likely induces a conformational change in β 2 -glycoprotein I, resulting in exposure of an antigenic epitope. Some of the autoantibodies present in the syndrome also interfere with clotting—and in fact, a prolonged activated partial thromboplastin time is characteristic of lupus erythematosus. All these antibodies have been collectively known as phospholipid antibodies, although this is inaccurate. Diagnosis of the syndrome is also problematic, because the criteria used can apply to a wide range of other illnesses. After a first episode of thrombosis, patients with antiphospholipid antibodies have a higher risk of recurrent thrombosis than do patients without antiphospholipid antibodies. 4 Retrospective studies suggest that patients with antiphospholipid antibodies have a high risk of recurrent thrombosis while receiving moderate-intensity warfarin therapy and that this risk is lower with a higher intensity of warfarin therapy. 5–7 However, these results must be interpreted with caution because the studies were retrospective case series, recurrent thrombosis was not confirmed by standardized methods, and the warfarin intensity at the time of the thrombotic events was uncertain. Furthermore, the patients in these studies attended special clinics where the staff had an interest in the management of complex problems in patients with antiphospholipid antibodies and the patients were therefore likely to be in a selected group at high risk for recurrent thrombosis. We studied patients with arterial or venous thrombosis and a positive test for antiphospholipid antibodies on an least 2 occasions at least 3 months apart from 13 tertiary-care rheumatology and thromboembolism clinics in eastern Canada. Patients were randomly assigned to receive warfarin to a target international normalized ratio of 2.0 to 3.0 or of 3.1 to 4.0.
Adapted from the well-written Introduction in Crowther MA, Ginsberg JS, Julian J, et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med 349:1133–1138, 2003.
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