Aspirin therapy and thromboxane biosynthesis in systemic lupus erythematosus

Abstract

Incomplete suppression of thromboxane biosynthesis during aspirin therapy is associated with increased cardiovascular risk. Since systemic lupus erythematosus (SLE) is associated with platelet activation and increased cardiovascular mortality, we compared thromboxane and prostacyclin biosynthesis in patients with SLE and control subjects, and measured inhibition of thromboxane excretion in aspirin-treated subjects. We measured the urinary excretion of 11-dehydro thromboxane B₂ (TXB₂) and 2,3-dinor 6-ketoPGF_1α (PGI-M), the stable metabolites of thromboxane A₂ and prostacyclin, respectively, in 74 patients with SLE and 70 controls. In subjects who were not receiving aspirin, TXB₂ excretion was higher in patients with SLE [0.40 ng/mg creatinine (0.26—0.64), median (interquartile range)] than controls [0.31 ng/mg creatinine (0.23—0.44)] (P = 0.04), and in these patients, TXB₂ excretion correlated with disease activity (rho = 0.28, P = 0.03) and tumor necrosis factor alpha (rho = 0.48, P < 0.001). Aspirin therapy resulted in significantly lower TXB₂ excretion in controls (P = 0.01), but not in patients with SLE (P = 0.10), compared with subjects not receiving aspirin. Prostacyclin biosynthesis did not differ among patients and controls, and was not affected by aspirin (P all >0.35). Thromboxane biosynthesis is increased in SLE and is associated with disease activity. Additionally, response to aspirin may be attenuated in some patients with SLE. Lupus (2007) 16, 981—986.

Keywords

systemic lupus erythematosus asprin resistance thromboxane prostacyclin oxidative stress

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