Determinants of enhanced thromboxane biosynthesis in patients with systemic lupus erythematosus

Objective. To evaluate the rate of thromboxane biosynthesis in patients wit h systemic lupus erythematosus (SLE), exploring the interplay between antip hospholipid antibodies (aPL) and 2 markers of endothelial perturbation: thr ombin generation and platelet activation. Methods. A comparison of 11-dehydro-thromboxane B-2, (TXB2) excretion, whic h is a marker of in vivo platelet activation, aPL, von Willebrand factor (V WF) and tissue plasminogen activator (tPA), which are 2 circulating markers of endothelial perturbation, and plasma levels of the prothrombin fragment F1+2, which is a marker of thrombin generation, was performed in 40 SLE pa tients and 40 healthy subjects, Thromboxane metabolite excretion was also m easured in 8 SLE patients before and after treatment with low-dose aspirin, Results. SLE patients had significantly higher 11-dehydro-TXB2 excretion, p lasma F1+2, vWF, and tPA levels than controls. A statistically significant correlation was found between plasma levels of vWF and tPA and excretion of thromboxane metabolite, Moreover, significantly higher 11-dehydro-TXB2 was found in patients with aPL positivity and endothelial perturbation. Low-do se aspirin suppressed 11-dehydro-TXB2 by 80%, suggesting a predominant plat elet source of enhanced thromboxane biosynthesis, After a median followup o f 48 months, all SLE patients who experienced major cardiovascular events h ad thromboxane metabolite excretion, aPL positivity, and signs of endotheli al perturbation, Conclusion, We have characterized a sensitive marker of platelet activation , which is abnormal in SLE patients who were positive for aPL and endotheli al perturbation, This analytical approach may help identify those patients at increased risk of thrombosis as potential candidates for antiplatelet th erapy.