Ongoing prothrombotic state in patients with antiphospholipid antibodies: a role for increased lipid peroxidation.
We measured the urinary excretion of Isoprostane F2alpha-III and Isoprostane-F2alpha-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-F2alpha-III (P =. 0001), Isoprostane-F2alpha-VI (P =.006), and plasma levels of the prothrombin fragment F1+2 (P =.0001). In antiphospholipid-positive patients, F1+2 significantly correlated with Isoprostane-F2alpha-III (Rho =.56, P =.017) and Isoprostane-F2alpha-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-F2alpha-III (P =.007) and Isoprostane-F2alpha-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.
Praticò
D
D
Institute of Clinical Medicine I, University "La Sapienza," Rome, Italy.
Ferro
D
D
Iuliano
L
L
Rokach
J
J
Conti
F
F
Valesini
G
G
FitzGerald
G A
GA
Violi
F
F
D000293:Adolescent; D000328:Adult; D017152:Antibodies, Antiphospholipid / Q000097:blood*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology / Q000652:urine; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis*; D011498:Protein Precursors / Q000032:analysis*; D011516:Prothrombin / Q000032:analysis*; D012016:Reference Values; D013997:Time Factors; D014810:Vitamin E / Q000627:therapeutic use*
C114340:8,12-iso-isoprostane F2alpha-III; C115626:8,12-iso-isoprostane F2alpha-VI; D017152:Antibodies, Antiphospholipid; D015415:Biomarkers; D010446:Peptide Fragments; D011498:Protein Precursors; D014810:Vitamin E; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D011516:Prothrombin; D005340:Fibrinogen; D015237:Dinoprost; D001205:Ascorbic Acid