Coexistence of Anti-Phospholipid Antibodies and Endothelial Perturbation in Systemic Lupus Erythematosus Patients With Ongoing Prothrombotic State

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Abstract
Background Anti-phospholipid antibodies (aPLs) were associated with an ongoing prothrombotic state in patients with systemic lupus erythematosus (SLE). Because aPLs are able to shift endothelial function toward procoagulant activity in vitro, we investigated the relationship among aPLs, ongoing prothrombotic state, and endothelial perturbation in SLE patients. Methods and Results We measured aPLs, anti-EC antibodies, circulating levels of prothrombin fragment F1+2 (F1+2), tumor necrosis factor-α (TNF-α), tissue-type plasminogen activator (TPA), and von Willebrand factor (vWF) in 43 SLE patients and 25 healthy subjects. Patients positive for aPLs (n=23) had a higher prevalence of anti-EC antibodies ( P =.02) and higher levels of F1+2 ( P =.003) than aPL(−) patients. Endothelial perturbation, defined by elevated plasma levels of both TPA and vWF, was significantly associated with aPL positivity ( P =.001). F1+2 >1 nmol/L (mean+2 SD of controls) was detected in all but one patient in whom aPL positivity and endothelial perturbation coexisted and in no aPL(+) patient without endothelial perturbation ( P =.0039). F1+2 was significantly correlated with vWF (ρ=.6, P =.004) and TPA (114 =.70, P =.0006) only in aPL(+) patients. Endothelial perturbation was closely associated with high values of TNF-α ( P =.0001), anti-phospholipid ( P =.001), and anti-EC antibodies ( P =.012). In 31 patients without a clinical history of thrombosis followed up for 3 years, aPL(+) patients with endothelial perturbation showed higher F1+2 and TNF-α values than aPL(+) patients without endothelial dysfunction. Conclusions This study shows that in SLE patients, aPL positivity is associated with an ongoing prothrombotic state only in the presence of endothelial perturbation. Our findings also suggest that aPLs and TNF-α might cooperate in inducing endothelial perturbation.