This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ferro, D. Articles by Violi, F. Search for Related Content PubMed PubMed Citation Articles by Ferro, D. Articles by Violi, F.

(Circulation. 1997;95:1425-1432.)
© 1997 American Heart Association, Inc.

Articles

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

Domenico Ferro, MD; Valerio Pittoni, MD; Claudio Quintarelli, MD; Stefania Basili, MD; Mirella Saliola, PhD; Costantino Caroselli, MD; Guido Valesini, MD; Francesco Violi, MD

From the Istituto di I Clinica Medica, Università "La Sapienza," Rome, Italy.

Correspondence to Prof Francesco Violi, Istituto di I Clinica Medica, Università di Roma "La Sapienza," Policlinico Umberto I, Viale del Policlinico, 00185 Roma, Italy.

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- (TNF-), 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 (=.6, P=.004) and TPA (114 =.70, P=.0006) only in aPL(+) patients. Endothelial perturbation was closely associated with high values of TNF- (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- 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- might cooperate in inducing endothelial perturbation.

Key Words: antibodies • endothelium • thrombosis • lupus

This article has been cited by other articles:

				B. Buttari, E. Profumo, V. Mattei, A. Siracusano, E. Ortona, P. Margutti, B. Salvati, M. Sorice, and R. Rigano Oxidized {beta}2-glycoprotein I induces human dendritic cell maturation and promotes a T helper type 1 response Blood, December 1, 2005; 106(12): 3880 - 3887. [Abstract] [Full Text] [PDF]

				G Davi and A Falco Oxidant stress, inflammation and atherogenesis Lupus, September 1, 2005; 14(9): 760 - 764. [Abstract] [PDF]

				R R Forastiero, M E Martinuzzo, and G F de Larranaga Circulating levels of tissue factor and proinflammatory cytokines in patients with primary antiphospholipid syndrome or leprosy related antiphospholipid antibodies Lupus, February 1, 2005; 14(2): 129 - 136. [Abstract] [PDF]

				M. Cugno, M. Cabibbe, M. Galli, P. L. Meroni, S. Caccia, R. Russo, B. Bottasso, and P. M. Mannucci Antibodies to tissue-type plasminogen activator (tPA) in patients with antiphospholipid syndrome: evidence of interaction between the antibodies and the catalytic domain of tPA in 2 patients Blood, March 15, 2004; 103(6): 2121 - 2126. [Abstract] [Full Text] [PDF]

				D. Hurlimann, A. Forster, G. Noll, F. Enseleit, R. Chenevard, O. Distler, M. Bechir, L. E. Spieker, M. Neidhart, B. A. Michel, et al. Anti-Tumor Necrosis Factor-{alpha} Treatment Improves Endothelial Function in Patients With Rheumatoid Arthritis Circulation, October 22, 2002; 106(17): 2184 - 2187. [Abstract] [Full Text] [PDF]

				M. Romano, M. Pomilio, S. Vigneri, A. Falco, P. L. Chiesa, F. Chiarelli, and G. Davi Endothelial Perturbation in Children and Adolescents With Type 1 Diabetes: Association with markers of the inflammatory reaction Diabetes Care, September 1, 2001; 24(9): 1674 - 1678. [Abstract] [Full Text] [PDF]

				D. Pratico, D. Ferro, L. Iuliano, J. Rokach, F. Conti, G. Valesini, G. A. FitzGerald, and F. Violi Ongoing Prothrombotic State in Patients With Antiphospholipid Antibodies: A Role for Increased Lipid Peroxidation Blood, May 15, 1999; 93(10): 3401 - 3407. [Abstract] [Full Text] [PDF]

				L. I. Kupferwasser, G. Hafner, S. Mohr-Kahaly, R. Erbel, J.u. Meyer, and H. Darius The presence of infection-related antiphospholipid antibodies in infective endocarditis determines a major risk factor for embolic events J. Am. Coll. Cardiol., April 1, 1999; 33(5): 1365 - 1371. [Abstract] [Full Text] [PDF]

				R Herrera-Esparza, O Barbosa-Cisneros, R Villalobos-Hurtado, and E Avalos-Diaz Renal expression of IL-6 and TNF{alpha} genes in lupus nephritis Lupus, March 1, 1998; 7(3): 154 - 158. [Abstract] [PDF]

				L. Iuliano, D. Pratico, D. Ferro, V. Pittoni, G. Valesini, J. Lawson, G. A. FitzGerald, and F. Violi Enhanced Lipid Peroxidation in Patients Positive for Antiphospholipid Antibodies Blood, November 15, 1997; 90(10): 3931 - 3935. [Abstract] [Full Text] [PDF]