© 1996 American Heart Association, Inc.
Articles |
Hypercoagulable State in Patients With Antiphospholipid Syndrome Is Related to High Induced Tissue Factor Expression on Monocytes and to Low Free Protein S
the Servicio de Hemoterapia y Hemostasia (J.-C.R., D.T., J.M., G.E., A.O.) and the Unidad de Enfermedades Autoinmunes Sistemicas (J.F., M.I.), Hospital Clinic i Provincial, Barcelona, Spain.
Correspondence to Dr J.C. Reverter, Servicio de Hemoterapia y Hemostasia, Hospital Clinic, Villarroel 170, Barcelona 08036, Spain.
Antiphospholipid antibodies (aPLs) are associated with thrombosis, but the mechanisms of this thrombotic tendency are unknown. We studied 56 patients (12 with systemic lupus erythematosus [SLE] and aPLs and previous thrombosis, 12 with SLE and aPLs but no thrombosis, 15 with SLE without aPLs or thrombosis, 11 with primary antiphospholipid syndrome with thrombosis, and 6 asymptomatic subjects with aPLs) to investigate the ability of aPLs to induce tissue factor (TF) expression on human normal monocytes. A double direct immunofluorescence technique (anti-CD14 and anti-TF) was used, and procoagulant activity in viable and disrupted cells was measured after plasma incubation for 6 hours at 37°C with normal mononuclear cells. Hemostasis regulatory proteins, prothrombin fragment 1+2, and thrombin–antithrombin III complex levels were determined. Increased TF expression and procoagulant activity were observed using plasma samples from SLE patients with aPLs and thrombosis (P<.01) and from primary antiphospholipid syndrome patients (P<.01) but not from patients with SLE and aPLs but no thrombosis, patients with SLE without aPLs, or asymptomatic patients with aPLs. Purified aPL immunoglobulins from one primary antiphospholipid syndrome and two SLE patients added to normal plasma showed a significant increase in both TF expression and procoagulant activity (P<.05) compared with purified aPL from two SLE patients without thrombosis. The addition of nonspecific IgG from three SLE patients without aPLs and from three control subjects did not increase TF expression. Low free protein S was seen in eight patients. Increased TF expression and low free protein S correlated with thrombosis (P<.01) and with higher prothrombin fragment 1+2 and thrombin–antithrombin III values (P<.01). These observations may contribute to a further understanding of the thrombotic risk in aPL patients.
Key Words: antiphospholipid syndrome • tissue factor • monocytes • free protein S • thrombosis
This article has been cited by other articles:
 |
|
 |
|
  M. K. Farmer-Boatwright and R. A.S. Roubey Venous Thrombosis in the Antiphospholipid Syndrome Arterioscler Thromb Vasc Biol, March 1, 2009; 29(3): 321 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Graham, I. Ford, R. Morrison, R. N. Barker, M. Greaves, and L.-P. Erwig Anti-Endothelial Antibodies Interfere in Apoptotic Cell Clearance and Promote Thrombosis in Patients with Antiphospholipid Syndrome J. Immunol., February 1, 2009; 182(3): 1756 - 1762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Lopez-Pedrera, P. Buendia, N. Barbarroja, E. Siendones, F. Velasco, and M. J. Cuadrado Antiphospholipid-Mediated Thrombosis: Interplay Between Anticardiolipin Antibodies and Vascular Cells Clinical and Applied Thrombosis/Hemostasis, January 1, 2006; 12(1): 41 - 45. [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]
|
|
|
|
 |
|
 H. Zhou, A. S. Wolberg, and R. A. S. Roubey Characterization of monocyte tissue factor activity induced by IgG antiphospholipid antibodies and inhibition by dilazep Blood, October 15, 2004; 104(8): 2353 - 2358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G Triolo, A Ferrante, A Accardo-Palumbo, F Ciccia, M Cadelo, A Castelli, A Perino, and G Licata IVIG in APS pregnancy Lupus, September 1, 2004; 13(9): 731 - 735. [Abstract] [PDF]
|
|
|
|
|
|
S S Pierangeli and E N Harris Probing antiphospholipid-mediated thrombosis: the interplay between anticardiolipin antibodies and endothelial cells Lupus, July 1, 2003; 12(7): 539 - 545. [Abstract] [PDF]
|
|
|
|
|
|
C.-S. Cho, M.-L. Cho, P. P. Chen, S.-Y. Min, S.-Y. Hwang, K.-S. Park, W.-U. Kim, D.-J. Min, J.-K. Min, S.-H. Park, et al. Antiphospholipid Antibodies Induce Monocyte Chemoattractant Protein-1 in Endothelial Cells J. Immunol., April 15, 2002; 168(8): 4209 - 4215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D Erkan, H W Zhang, R C Shriky, and J T Merrill Dual antibody reactivity to {beta}2-glycoprotein I and protein S: increased association with thrombotic events in the antiphospholipid syndrome Lupus, April 1, 2002; 11(4): 215 - 220. [Abstract] [PDF]
|
|
|
|
 |
|
 J. H. Rand Molecular Pathogenesis of the Antiphospholipid Syndrome Circ. Res., January 11, 2002; 90(1): 29 - 37. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Arepally and I. M. Mayer Antibodies from patients with heparin-induced thrombocytopenia stimulate monocytic cells to express tissue factor and secrete interleukin-8 Blood, August 15, 2001; 98(4): 1252 - 1254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Male, L. Mitchell, J. Julian, P. Vegh, P. Joshua, M. Adams, M. David, and M. E. Andrew Acquired activated protein C resistance is associated with lupus anticoagulants and thrombotic events in pediatric patients with systemic lupus erythematosus Blood, February 15, 2001; 97(4): 844 - 849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Pierangeli, R. G. Espinola, X. Liu, and E. N. Harris Thrombogenic Effects of Antiphospholipid Antibodies Are Mediated by Intercellular Cell Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, and P-Selectin Circ. Res., February 2, 2001; 88(2): 245 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Khajuria and D. S. Houston Induction of monocyte tissue factor expression by homocysteine: a possible mechanism for thrombosis Blood, August 1, 2000; 96(3): 966 - 972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J T Merrill and R G Lahita Sex hormone binding globulins and atherosclerotic risk in systemic lupus Lupus, March 1, 2000; 9(3): 217 - 222. [Abstract] [PDF]
|
|
|
|
|
|
S. Visvanathan and H. P. McNeil Cellular Immunity to {beta}2-Glycoprotein-1 in Patients with the Antiphospholipid Syndrome J. Immunol., June 1, 1999; 162(11): 6919 - 6925. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Pierangeli, M. Colden-Stanfield, X. Liu, J. H. Barker, G. L. Anderson, and E. N. Harris Antiphospholipid Antibodies From Antiphospholipid Syndrome Patients Activate Endothelial Cells In Vitro and In Vivo Circulation, April 20, 1999; 99(15): 1997 - 2002. [Abstract] [Full Text] [PDF]
|
|