Determinants of enhanced thromboxane biosynthesis in patients with systemic lupus erythematosus

✍ Scribed by Domenico Ferro; Stefania Basili; Salvatore Roccaforte; Manuela Di Franco; Francesco Cipollone; Giovanni Ciabattoni; Giovanni Davì

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 168 KB
• Volume: 42
• Category: Article
• ISSN: 0004-3591
• DOI: 10.1002/1529-0131(199912)42:12<2689::aid-anr27>3.0.co;2-x

✦ Synopsis

To evaluate the rate of thromboxane biosynthesis in patients with systemic lupus erythematosus (SLE), exploring the interplay between antiphospholipid antibodies (aPL) and 2 markers of endothelial perturbation: thrombin generation and platelet activation.

Methods. A comparison of 11-dehydrothromboxane B 2 (TXB 2 ) excretion, which is a marker of in vivo platelet activation, aPL, von Willebrand factor (vWF) 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 patients and 40 healthy subjects. Thromboxane metabolite excretion was also measured in 8 SLE patients before and after treatment with low-dose aspirin.

Results. SLE patients had significantly higher 11-dehydro-TXB 2 excretion, plasma 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-TXB 2 was found in patients with aPL positivity and endothelial perturbation. Low-dose aspirin suppressed 11-dehydro-TXB 2 by 80%, suggesting a predominant platelet source of enhanced thromboxane biosynthesis. After a median followup of 48 months, all SLE patients who experienced major cardiovascular events had thromboxane metabolite excretion, aPL positivity, and signs of endothelial perturbation.

Conclusion.

We have characterized a sensitive marker of platelet activation, which is abnormal in SLE patients who were positive for aPL and endothelial perturbation. This analytical approach may help identify those patients at increased risk of thrombosis as potential candidates for antiplatelet therapy.