Thrombosis Research
Volume 121, Issue 3 , Pages 319-325 , 2007

Platelet activation rather than endothelial injury identifies risk of thrombosis in subjects positive for antiphospholipid antibodies

Received 24 October 2006 ,Revised 25 April 2007 ,Accepted 26 April 2007.

References 

  1. Triplett DA. Protean clinical presentations of antiphospholipid antibodies (APA). Thromb Haemost. 1995;74:329–337
  2. Galli M, Barbui T. Antiprothrombin antibodies: detection and clinical significance in the antiphospholipid syndrome. Blood. 1999;93:2149–2157
  3. Lockshin MD, Sammaritano LR, Schwartzman S. Validation of the Sapporo criteria for antiphospholipid syndrome. Arthritis Rheum. 2000;43:440–443
  4. Arnout J. Antiphospholipid syndrome: diagnostic aspects of lupus anticoagulants. Thromb Haemost. 2001;86:83–91
  5. Levine JS, Branch DW, Rauch J. The antiphospholipid syndrome. N Engl J Med. 2002;346:752–763
  6. McIntyre JA, Wagenknecht DR, Faulk WP. Antiphospholipid antibodies: discovery, definitions, detection and disease. Prog Lipid Res. 2003;42:176–237
  7. Hughes GRV, Harris EN, Gharavi AE. The anticardiolipin syndrome. J Rheumatol. 1985;13:486–489
  8. Khamashta MA, Harris EN, Gharavi AE, Derue G, Gil A, Vazquez JJ, et al. Immune mediated mechanism for thrombosis antiphospholipids antibody binding to platelet membranes. Ann Rheum Dis. 1988;47:849–852
  9. Out HJ, deGroot PG, vanVliet M, deGast GC, Nieuwenhuis HK, Derksen RH. Antibodies to platelets in patients with anti-phospholipid antibodies. Blood. 1991;77:2655–2659
  10. Nozima J, Suehisa E, Kuratsune H, Machi T, Koike T, Kitani T, et al. Platelet activation induced by combined effects of anticardiolipin and lupus anticoagulant IgG antibodies in patients with systemic lupus erythematosus: possible association with thrombotic and thrombocytopenic complications. Thromb Haemost. 1999;81:431–436
  11. Martinuzzo ME, Maclouf J, Carreras LO, Levy-Toledano S. Antiphospholipid antibodies enhance thrombin induced platelet activation and thromboxane formation. Thromb Haemost. 1993;70:667–671
  12. Tokita S, Arai M, Yamamoto N, Katagiri Y, Tanoue K, Igarashi K, et al. Specific cross reaction of IgG anti-phospholipid antibody with platelet glycoprotein IIIa. Thromb Haemost. 1996;75:168–174
  13. Zhang J, McCrae R. Annexin A2 mediates endothelial cell activation by antiphospholipid / andti-beta-2-glycoprotein I antibodies [with editorial p1845]. Blood. 2005;105:1964–1969
  14. Dueymes M, Levy Y, Ziporen L, Jamin C, Piette JC, Shoenfeld Y, et al. Do some antiphospholipid antibodies target endothelial cells?. Ann Med Interne. 1996;147(Suppl 1):22–23
  15. Papa ND, Rascho E, Moroni G, Panzeri P, Borghi MO, Ponticelli C, et al. Anti-endothelial cell IgG fractions from systemic lupus erythematosus patients bind to human endothelial cells and induce a proadhesive and proinflammatory phenotype in vivo. Lupus. 1999;8:423–429
  16. Carvalho D, Savage CO, Isenberg D, DPearson J. IgG anti-endothelial cell autoantibodies from patients with systemic lupus erythematosus or systemic vasculitis stimulate the release of two endothelial cell-derived mediators, which enhance adhesion molecule expression and leukocyte adhesion in an autocrine manner. Arthritis Rheum. 1999;42:631–640
  17. Williams FMK, Parmar K, Hughes GRV, Hunt BJ. Systemic endothelial cell markers in primary antiphospholipid syndrome. Thromb Haemost. 2000;84:742–746
  18. Simantov R, LaSala J, Lo S, Gharavi A, Sammaritano L, Salmon J. Activation of cultured vascular endothelial cells by antiphospholipid antibodies. J Clin Invest. 1995;96:2211–2219
  19. Oosting J, Derksen RH, Blokzijl L, Sixma L, deGroot PG. Antiphospholipid antibody positive sera enhance endothelial cell procoagulant activity-studies in a thrombosis model. Thromb Haemost. 1992;68:278–284
  20. McCrae KR, DeMichele A, Samuels P, Roth D, Kuo A, Meng Q, et al. Detection of endothelial cell-reactive immunoglobulin in patients with antiphospholipid antibodies. Br J Haematol. 1991;79:595–605
  21. Simantov R, Lo SK, Gharavi A, Sammaritano LR, Salmon JE, Silverstein RL. Antiphospholipid antibodies activate vascular endothelial cells. Lupus. 1996;5:440–441
  22. Meroni PL, Raschi E, Testoni C, Tincani A, Balestrieri G. Antiphospholipid antibodies and the endothelium. Rheum Dis Clin North Am. 2001;27(s):587–602
  23. DelPapa N, Meroni PL, Tincani A, Harris EN, Pierangeli SS, Barcellini W, et al. Relationship between anti-phospholipid and anti-endothelial cell antibodies: further characterization of the reactivity on resting and cytokine-activated endothelial cells. Clin Exp Rheumatol. 1992;10:37–42
  24. Espinola RG, Liu X, Golden-Stanfield M, Hall J, Harris EN, Pierangeli SS. E-selectin mediates pathogenic effects of antiphospholipid antibodies. J Thromb Haemost. 2003;1:843–848
  25. Martinuzzo ME, Forastiero RR, Carreras LO. Increased plasma thrombomodulin in different subgroups of patients with antiphospholipid and anti fl2 glycoprotein 1 antibodies. Thromb Haemost. 1996;75:972–973
  26. Hill MB, Phipps JL, Hughes P, Greaves M. Anti-endothelial cell antibodies in primary antiphospholipid syndrome and SLE: patterns of reactivity with membrane antigens on microvascular and umbilical venous cell membranes. Br J Haematol. 1998;103:416–421
  27. Greaves M. Antiphospholipid antibodies and thrombosis [for letters in response, see v354:71–3]. Lancet. 1999;353:1348–1353
  28. Vermylen J, Hoylaerts MF, Arnout J. Antibody-mediated thrombosis. Thromb Haemost. 1997;78:420–426
  29. Galli M, Finazzi G, Barbui T. Antiphospholipid antibodies: predictive value of laboratory tests. Thromb Haemost. 1997;78:75–78
  30. Esmon NL, Smirnov MD, Esmon CT. Thrombogenic mechanisms of antiphospholipid antibodies (State of the Art). Thromb Haemost. 1997;78:79–82
  31. Arnout J, Vermylen J. Current status and implications of autoimmune antiphospholipid antibodies in relation to thrombotic disease. J Thromb Haemost. 2003;1:931–942
  32. Roubey RAS. Immunology of the antiphospholipid antibody syndrome. Arthritis Rheum. 1996;39:1444–1454
  33. Bick RL, Pegram M. Syndromes of hypercoagulability and thrombosis: a review. Semin Thromb Hemost. 1994;20:109–132
  34. Oosting J, Derkson RHWM, Bobbink IWG, Hackeng TM, Bouma BN, deGroot PG. Antiphospholipid antibodies directed against a combination of phospholipids with prothrombin, protein C, or protein S: an explanation for their pathogenic mechanisms?. Blood. 1993;81:2618–2625
  35. Mercier E, Quere I, Mares P, Gris JC. Primary recurrent miscarriages and anti-beta-2-glycoprotein I IgG antibodies induce an acquired activated protein C resistance that can be detected by the modified activated protein C resistance test (Letter). Blood. 1998;92:2993–2994
  36. Galli M, Ruggeri L, Barbui T. Differential effects of anti-fl2-glycoprotein 1 and anti-prothrombin antibodies on the anticoagulant activity of activated protein C. Blood. 1998;91:1999–2004
  37. Munakata Y, Saito T, Mutsada K, Seino J, Shibata S, Sasoki T. Detection of complement-fixing antiphospholipid antibodies in associated with thrombosis. Thromb Haemost. 2000;83:728–731
  38. Stewart MW, Etches WS, Gordon PA. Antiphospholipid antibody-dependent C5b–9 formation. Brit J Haematol. 1997;96:451–457
  39. Horstman LL, Ahn YS. Platelet microparticles: a wide-angle perspective (Review). Crit Rev Oncol/Hematol. 1999;30:111–142
  40. Horstman LL, Jy W, Jimenez JJ, Ahn YS. Endothelial microparticles as markers of endothelial dysfunction [Review]. Front Biosci. 2004;9:1118–1135
  41. Bidot CJ, Jy W, Horstman LL, Huang H, Jimenez JJ, Yaniz M, et al. Factor VII/VIIa: a new antigen in the antiphospholipid antibody syndrome. Br J Haematol. 2003;120:618–626
  42. Bidot CJ, Jy W, Horstman LL, Ahn ER, Jimenez JJ, Yaniz M, et al. Antiphospholipid antibodies in immune thrombocytopenic purpura tend to emerge in exacerbation and decline in remission. Br J Haematol. 2004;128:366–372
  43. Arnout W, Meijer P, Vermylen J. Lupus anticoagulant testing in Europe: an analysis of results from the First European Concerted Action on Thrombophilia (ECAT) Survey using plasmas spiked with monoclonal antibodies against human?2-glycoprotein 1. Thromb Haemost. 1999;81:929–934
  44. Reber G, Schousboe I, Tincani A, Sanmarco M, Kveder T, deMoerloose P, et al. Inter-laboratory variability of anti-fl2-glycoprotein I measurement: collaborative study in the frame of the European Forum on Antiphospholipid Antibodies Standardization Group. Thromb Haemost. 2002;88:66–73
  45. Tincani A, Allegri F, Sanmarco M, Cinquini M, Taglietti M, Balestrieri G, et al. Anticardiolipin antibody assay: a methodological analysis for a better consensus in routine determinations. A Cooperative Project of the European Antiphospholipid Forum. Thromb Haemost. 2001;86:575–583
  46. Jimenez J, Jy W, Mauro L, Horstman L, Ahn Y. Elevated endothelial microparticles in thrombotic thrombocytopenic purpura (TTP): findings from brain and renal microvascular cell culture and patients with active disease. Br J Haematol. 2001;112:81–90
  47. Minagar A, Jy W, Jimenez JJ, Mauro LM, Horstman LL, Ahn YS, et al. Elevated plasma endothelial microparticles in multiple sclerosis. Neurology. 2001;56:1319–1324
  48. Jy W, Horstman LL, Jimenez JJ, Ahn YS. Measuring circulating cell-derived microparticles [Forum Article]. J Thromb Haemost. 2004;2:1842–1851
  49. Bernal-Mizrachi L, Jy W, Jimenez JJ, Pastor J, Mauro L, Horstman LL, et al. High levels of circulating endothelial microparticles in patients with acute coronary syndromes. Am Heart J. 2003;145:962–970
  50. Jimenez JJ, Jy W, Mauro LM, Horstman LL, Soderland C, Ahn YS. Endothelial microparticles released in thrombotic thrombocytopenic purpura express von Willebrand factor and markers of endothelial activation. Br J Haematol. 2003;123:896–902
  51. Ruiz-Torres MP, Casiraghi F, Galbusera M, Macconi D, Gastoldi S, Todeschini M, et al. Complement activation: the missing link between ADAMTS-13 deficiency and microvascular thrombosis of thrombotic microangiopathies. Thromb Haemost. 2005;93:443–452
  52. Galli M, Luciani D, Bertolini G, Barbui T. Lupus anticoagulants are stronger risk factors of thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood. 2003;101:1827–1832
  53. Horbach DA, vanOort E, Donders RCJM, Derksen RHWM, deGroot PG. Lupus anticoagulant is the strongest risk factor for both venous and arterial thrombosis in patients with systemic lupus erythematosus. Comparison between different assays for the detection of antiphospholipid antibodies. Thromb Haemost. 1996;76:916–924
  54. Brandt JT, Triplett DA, Alving B, Scharrer I. Criteria for the diagnosis of lupus anticoagulants: an update (on behalf of the SSC of ISTH). Thromb Haemost. 1995;74(4):1185–1190

 This work is supported largely by the Wallace H. Coulter Foundation.

PII: S0049-3848(07)00204-6

doi: 10.1016/j.thromres.2007.04.014

Thrombosis Research
Volume 121, Issue 3 , Pages 319-325 , 2007