Determinants of enhanced thromboxane biosynthesis in patients with systemic lupus erythematosus.
OBJECTIVE
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 B2 (TXB2) 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-TXB2 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-TXB2 was found in patients with aPL positivity and endothelial perturbation. Low-dose aspirin suppressed 11-dehydro-TXB2 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.


CONCLUSIONS
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.
Ferro
D
D
University of Rome La Sapienza, Italy.
Basili
S
S
Roccaforte
S
S
Di Franco
M
M
Cipollone
F
F
Ciabattoni
G
G
Davì
G
G
D000328:Adult; D017152:Antibodies, Antiphospholipid / Q000097:blood; D000941:Antigens / Q000097:blood; D001241:Aspirin / Q000008:administration & dosage; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007511:Ischemia / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism; D020521:Stroke / Q000378:metabolism; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D013931:Thromboxanes / Q000096:biosynthesis*; D010959:Tissue Plasminogen Activator / Q000276:immunology; D020246:Venous Thrombosis / Q000378:metabolism; D014841:von Willebrand Factor / Q000032:analysis
D017152:Antibodies, Antiphospholipid; D000941:Antigens; D013931:Thromboxanes; D014841:von Willebrand Factor; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D010959:Tissue Plasminogen Activator; D001241:Aspirin