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Blood, Vol. 93 No. 10 (May 15), 1999:
pp. 3401-3407
Ongoing Prothrombotic State in Patients With Antiphospholipid
Antibodies: A Role for Increased Lipid Peroxidation
Domenico Praticò,
Domenico Ferro,
Luigi Iuliano,
Joshua Rokach,
Fabrizio Conti,
Guido Valesini,
Garret A. FitzGerald, and
Francesco Violi
From the Institute of Clinical Medicine I, University "La
Sapienza," Rome, Italy; and the Center for Experimental
Therapeutics, University of Pennsylvania, Philadelphia, PA.
We measured the urinary excretion of Isoprostane
F2 -III and Isoprostane-F2-VI, two markers
of in vivo lipid peroxidation, and the circulating levels of the
prothrombin fragment F1+2, a marker of thrombin generation, in 18 antiphospholipid antibodies-positive patients, in 18 antiphospholipid
antibodies-negative patients with systemic lupus erythematosus, and in
20 healthy subjects. Furthermore, 12 patients positive for
antiphospholipid antibodies were treated with (n = 7) or without (n
= 5) antioxidant vitamins (vitamin E at 900 IU/d and vitamin C at
2,000 mg/d) for 4 weeks. Compared with antiphospholipid
antibodies-negative patients, antiphospholipid antibodies-positive
patients had higher urinary values of Isoprostane-F2-III
(P = .0001), Isoprostane-F2-VI (P = .006), and plasma levels of the prothrombin fragment F1+2 (P
= .0001). In antiphospholipid-positive patients, F1+2 significantly correlated with Isoprostane-F2-III (Rho = .56, P = .017) and Isoprostane-F2-VI (Rho
= .61, P = .008). After 4 weeks of supplementation with
antioxidant vitamins, we found a significant decrease in F1+2 levels
(P < .005) concomitantly with a significant reduction of both
Isoprostane-F2-III (P = .007) and
Isoprostane-F2-VI (P < .005). No change of these variables was observed in patients not receiving antioxidant treatment. This study suggests that lipid peroxidation might contribute to the activation of clotting system in patients positive for antiphospholipid antibodies.
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