Production of prostacyclin and thromboxane in lupus pregnancies: effect of small dose of aspirin

OBJECTIVES: To find out whether the tendency toward poor outcome in lupus pregnancies could be explained by changes in prostacyclin/thromboxane production, to relate these changes to the presence of antiphospholipid antibodies, and to study the potential benefits of low-dose aspirin. METHODS: We followed the urinary output of prostacyclin metabolites (6-keto-prostaglandin PG]F1 alpha, 2,3-dinor-6-keto-PGF1 alpha) and thromboxane metabolites (thromboxane B2, 2,3-dinor-thromboxane B2) using high-pressure liquid chromatography followed by radioimmunoassay. We studied 14 pregnant women with systemic lupus erythematosus (SLE), of whom six had detectable antiphospholipid antibodies. The patients were randomized by a computerized program to receive either 50 mg aspirin daily (six women) or placebo (eight women). Nine healthy pregnant women served as controls. RESULTS: The production of prostacyclin was normal in early pregnancy in SLE patients but was reduced during late gestation in those without antiphospholipid antibodies. The production of thromboxane was increased in SLE patients compared with controls, and this increase was highest (two-to threefold rise) when antiphospholipid antibodies were detectable. Aspirin eliminated thromboxane dominance without affecting prostacyclin production. CONCLUSION: These data suggest that the presence of antiphospholipid antibodies in SLE patients may trigger thromboxane dominance, possibly contributing to the adverse outcome of these pregnancies. This thromboxane dominance can be eliminated with aspirin.