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15th International Congress on Antiphospholipid Antibodies Task Force on Antiphospholipid Syndrome Treatment Trends Report

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Abstract

A challenge in antiphospholipid syndrome (APS) is to translate targeted therapies from animal and in vitro models to clinical trials. The 15th International Congress on Antiphospholipid Antibodies (aPL) Task Force on Treatment Trends summarized new developments in APS targeted treatment since the 14th International Congress on aPL (September 2013). The task force also discussed additional treatments and/or pathways that can be considered in the management of aPL-positive patients.

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References

  1. Miyakis S, Lockshin MD, Atsumi D, et al. International consensus statement on an update of the preliminary classification criteria for antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295–306.

    Article  CAS  PubMed  Google Scholar 

  2. Pengo V, Rufatti A, Legnani C, et al. Clinical course of high-risk patients diagnosed with antiphospholipid syndrome. J Thromb Haemost. 2010;8:237–42.

    Article  CAS  PubMed  Google Scholar 

  3. Erkan D, Aguiar CL, Andrade D, et al. 14th international congress on antiphospholipid antibody task force report on antiphospholipid syndrome treatment trends. Autoimmun Rev. 2014;13:685–96.

    Article  CAS  PubMed  Google Scholar 

  4. Yazici A, Unlu O, Erkan D. A systematic review of direct oral anticoagulant use in antiphospholipid syndrome. Lupus. 2016;25(Supp 1S):92 (abstract).

    Google Scholar 

  5. Malec K, Góralczyk T, Undas A. The use of direct oral anticoagulants in 56 patients with antiphospholipid syndrome. Thromb Res. 2017;152:93–97.

    Google Scholar 

  6. Cohen H, Hunt BJ, Efthymiou M, et al. RAPS trial investigators. Rivaroxaban versus warfarin to treat patients with thrombotic antiphospholipid syndrome, with or without systemic lupus erythematosus (RAPS): a randomized, controlled, open-label, phase 2/3, non-inferiority trial. Lancet Haematol. 2016;3:e426–36.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Pengo V, Banzato A, Bison E, Zoppellaro G, Padayattil Jose S, Denas G. Efficacy and safety of rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome: rationale and design of the trial on rivaroxaban in AntiPhospholipid syndrome (TRAPS) trial. Lupus. 2016;25:301–6.

    Article  CAS  PubMed  Google Scholar 

  8. Woller SC, Stevens SM, Kaplan DA. Apixaban for the secondary prevention of thrombosis among patients with antiphospholipid syndrome: study rationale and design (ASTRO-APS). Clin Appl Thromb Hemost. 2016;22:239–47.

    Article  CAS  PubMed  Google Scholar 

  9. Danesh FR, Anel RL, Zeng L, Lomasney J, Sahai A, Kanwar YS. Immunomodulatory effects of HMG-CoA reductase inhibitors. Arch Immunol Ther Exp. 2003;51:139–48.

    CAS  Google Scholar 

  10. Meroni PL, Raschi E, Testoni C, et al. Statins prevent endothelial cell activation induced by antiphospholipid (anti-beta2-glycoprotein I) antibodies: effect on the proadhesive and proinflammatory phenotype. Arthritis Rheum. 2001;44:2870–8.

    Article  CAS  PubMed  Google Scholar 

  11. Redecha P, Franzke CW, Ruf W, Mackman N, Girardi G. Neutrophil activation by the tissue factor/factor VIIa/PAR2 axis mediates fetal death in a mouse model of antiphospholipid syndrome. J Clin Invest. 2008;118:3453–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Ferrara DE, Liu X, Espinola RG, et al. Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model. Arthritis Rheum. 2003;48:3272–9.

    Article  CAS  PubMed  Google Scholar 

  13. López-Pedrera C, Ruiz-Limón P, Aguirre MÁ, et al. Global effects of fluvastatin on the prothrombotic status of patients with antiphospholipid syndrome. Ann Rheum Dis. 2011;70:675–82.

    Article  PubMed  CAS  Google Scholar 

  14. Erkan D, Willis R, Murthy VL, et al. A prospective open-label pilot study of fluvastatin on proinflammatory and prothrombotic biomarkers in antiphospholipid antibody positive patients. Ann Rheum Dis. 2014;73:1176–80.

    Article  CAS  PubMed  Google Scholar 

  15. Lefkou E, Mamopoulos A, Dagklis T, Vosnakis C, Rousso D, Girardi G. Pravastatin improves pregnancy outcomes in obstetric antiphospholipid syndrome refractory to antithrombotic therapy. J Clin Invest. 2016;126:2933–40.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kaesemeyer WH, Caldwell RB, Huang J, Caldwell RW. Pravastatin sodium activates endothelial nitric oxide synthase independent of its cholesterol-lowering actions. J Am Coll Cardiol. 1999;33:234–41.

    Article  CAS  PubMed  Google Scholar 

  17. López-Pedrera C, Buendía P, Cuadrado MJ, et al. Antiphospholipid antibodies from patients with the antiphospholipid syndrome induce monocyte tissue factor expression through the simultaneous activation of NF-kappaB/Rel proteins via the p38 mitogen-activated protein kinase pathway, and of the MEK-1/ERK pathway. Arthritis Rheum. 2006;54:301–31.

    Article  PubMed  CAS  Google Scholar 

  18. Girardi G. Can statins prevent pregnancy complications? J Reprod Immunol. 2014;102:161–7.

    Article  CAS  Google Scholar 

  19. Lockshin MD, Pierangeli SS. Statins for the treatment of obstetric complications in antiphospholipid syndrome? J Reprod Immunol. 2010;84:206.

    Article  CAS  PubMed  Google Scholar 

  20. Costantine MM. Safety and pharmacokinetics of pravastatin used for the prevention of preeclampsia in high-risk pregnant women: a pilot randomized controlled trial. Am J Obstet Gynecol. 2016;214:720.

    PubMed  Google Scholar 

  21. Bateman BT, Hernandez-Diaz S, Fischer MA, et al. Statins and congenital malformations: cohort study. BMJ. 2015;350:h1484.

    Article  Google Scholar 

  22. Kahn P, Ramanujman M, Bethunaickan R, et al. Prevention of murine antiphospholipid syndrome by BAFF blockade. Arthritis Rheum. 2008;58:2824–34.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Trappe R, Loew A, Thuss-Patience P, Dorken B, Riess H. Successful treatment of thrombocytopenia in primary antiphospholipid antibody syndrome with the anti-CD20 antibody rituximab—monitoring of antiphospholipid and anti-GP antibodies: a case report. Ann Hematol. 2006;85:134–5.

    Article  CAS  PubMed  Google Scholar 

  24. Erdozain JG, Ruiz-Irastorza G, Egurbide MV, Aguirre C. Sustained response to rituximab of autoimmune hemolytic anemia associated with antiphospholipid syndrome. Haematologica. 2004;89:ECR34 [Abstract].

    Google Scholar 

  25. Tenedios F, Erkan D, Lockshin MD. Rituximab in the primary antiphospholipid syndrome (PAPS). Arthritis Rheum. 2005;52:4078.

    Google Scholar 

  26. Berman H, Rodríguez-Pintó I, Cervera R, et al. Rituximab use in the catastrophic antiphospholipid syndrome: descriptive analysis of the CAPS registry patients receiving rituximab. Autoimmun Rev. 2013;12:1085–90.

    Article  CAS  PubMed  Google Scholar 

  27. Erkan D, Vega J, Ramon G, Kozora E, Lockshin MD. Rituximab in antiphospholipid syndrome (RITAPS) — a pilot open-label phase II prospective trial for non-criteria manifestations of antiphospholipid antibodies. Arthritis Rheum. 2013;65:464–71.

    Article  CAS  PubMed  Google Scholar 

  28. Yazirli B, Yazici A, Erkan D. Belimumab in primary antiphospholipid syndrome. Lupus. 2016;25(Supp 1S):94 (abstract).

    Google Scholar 

  29. Girardi G, Berman J, Redecha P, et al. Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. J Clin Invest. 2003;112:1644–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Simantov R, LaSala JM, Lo SK, et al. Activation of cultured vascular endothelial cells by antiphospholipid antibodies. J Clin Invest. 1995;96:2211–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ritis K, Doumas M, Mastellos D, et al. A novel C5a receptor-tissue factor crosstalk in neutrophils links innate immunity to coagulation pathways. J Immunol. 2006;177:4794–802.

    Article  CAS  PubMed  Google Scholar 

  32. Redecha P, Tilley R, Tencati M, et al. Tissue factor: a link between C5a and neutrophil activation in antiphospholipid antibody induced fetal injury. Blood. 2007;110:2423–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Pierangeli SS, Colden-Stanfield M, Liu X, Barker JH, Anderson GL, Harris EN. Antiphospholipid antibodies from antiphospholipid syndrome patients activate endothelial cells in vitro and in vivo. Circulation. 1999;99:1997–2002.

    Article  CAS  PubMed  Google Scholar 

  34. Pierangeli SS, Girardi G, Vega-Ostergard M, Liu X, Espinola RG, Salmon J. Requirement of activation of complement C3 and C5 for antiphospholipid antibody-mediated thrombophilia. Arthritis Rheum. 2005;52:2120–4.

    Article  CAS  PubMed  Google Scholar 

  35. Licht C, Fremeaux-Bacchi V. Hereditary and acquired complement dysregulation in membranoproliferative glomerulonephritis. Thromb Haemost. 2009;101:271–8.

    CAS  PubMed  Google Scholar 

  36. Erkan D, Salmon J. The role of complement in thrombotic Angiopathies and antiphospholipid syndrome. Turk J Haematol. 2016;33:1–7.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Hillmen P, Hall C, Marsh JC, et al. Effect of eculizumab on Hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2004;350:552–9.

    Article  CAS  PubMed  Google Scholar 

  38. Lonze BE, Singer AL, Montgomery RA. Eculizumab and renal transplantation in a patient with CAPS. N Engl J Med. 2010;362:1744–5.

    Article  CAS  PubMed  Google Scholar 

  39. Gueler F, Rong S, Gwinner W, et al. Complement 5a receptor inhibition improves renal allograft survival. J Am Soc Nephrol. 2008;19:2302–12.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Frémeaux-Bacchi V, Legendre CM. The emerging role of complement inhibitors in transplantation. Kidney Int. 2015;88:967–73.

    Article  PubMed  CAS  Google Scholar 

  41. Fakhouri F, Hourmant M, Campistol JM, et al. Terminal complement inhibitor eculizumab in adult patients with atypical hemolytic uremic syndrome: a single-arm, open-label trial. Am J Kidney Dis. 2016;68:84–93.

    Article  CAS  PubMed  Google Scholar 

  42. Lonze BE, Zachary AA, Magro CM, et al. Eculizumab prevents recurrent antiphospholipid antibody syndrome and enables successful renal transplantation. Am J Transplant. 2014;14:459–65.

    Article  CAS  PubMed  Google Scholar 

  43. Canaud G, Kamar N, Anglicheau D, et al. Eculizumab improves post-transplant thrombotic microangiopathy due to antiphospholipid syndrome recurrence but fails to prevent chronic vascular changes. Am J Transplant. 2013;13:2179–85.

    Article  CAS  PubMed  Google Scholar 

  44. Meroni PL, Macor P, Durigutto P, et al. Complement activation in antiphospholipid syndrome and its inhibition to prevent rethrombosis after arterial surgery. Blood. 2016;127:365–7.

    Article  CAS  PubMed  Google Scholar 

  45. Arachchillage DR, Mackie IJ, Efthymiou M, et al. Rivaroxaban limits complement activation compared with warfarin in antiphospholipid. J Thromb Haemost. 2016;14:2177–86

    Google Scholar 

  46. Amara U, Flierl MA, Rittirsch D, et al. Intercommunication between the complement and coagulation systems. J Immunol. 2010;185:5628–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Agostinis C, Durigutto P, Sblattero D, et al. MBB2 a non-complement-fixing antibody to β2 glycoprotein I as a novel therapy for antiphospholipid syndrome. Blood. 2014;123:3478–87.

    Article  CAS  PubMed  Google Scholar 

  48. Steinkasserer A, Estaller C, Weiss EH, Sim RB, Day AJ. Complete nucleotide and deduced amino acid sequence of human beta 2-glycoprotein I. Biochem J. 1991;277:387–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ioannou Y, Pericleous C, Giles I, Latchman DS, Isenberg DA, Rahman A. Binding of antiphospholipid antibodies to discontinuous epitopes on domain I of human beta(2)-glycoprotein I: mutation studies including residues R39 to R43. Arthritis Rheum. 2007;56:280–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Giannakopoulos B, Passam F, Rahgozar S, Krilis SA. Current concepts on the pathogenesis of the antiphospholipid syndrome. Blood. 2007;109:422–30.

    Article  CAS  PubMed  Google Scholar 

  51. Reddel SW, Wang YX, Sheng YH, Krilis SA. Epitope studies with anti-beta 2-glycoprotein I antibodies from autoantibody and immunized sources. J Autoimmun. 2000;15:91–6.

    Article  CAS  PubMed  Google Scholar 

  52. Ioannou Y, Romay-Penabad Z, Pericleous C, et al. In vivo inhibition of antiphospholipid antibody-induced pathogenicity utilizing the antigenic target peptide domain I of beta2-glycoprotein I: proof of concept. J Thromb Haemost. 2009;7:833–42.

    Article  CAS  PubMed  Google Scholar 

  53. Pericleous C, Miles J, Esposito D, et al. Evaluating the conformation of recombinant domain I of beta(2)-glycoprotein I and its interaction with human monoclonal antibodies. Mol Immunol. 2011;49:56–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Pericleous C, Disu T, Miles J, et al. Peptide and NMR spectroscopy studies of recombinant domain I confirm conformationally correct domain I and non-linear epitope binding to anti-domain I antiphospholipid antibodies. Arthritis Rheum. 2010;62:S563–4.

    Google Scholar 

  55. McDonnell T, Pericleous C, Laurine E, et al. Development of a high yield expression and purification system for domain I of Beta-2-glycoprotein I for the treatment of APS. BMC Biotechnol. 2015;15:104.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. McDonnell T, Pericleous C, Ioannou Y, Giles I, Rahman A. PEGylated recombinant domain I of beta-2-glycoprotein I, a potential therapeutic agent for antiphospholipid syndrome, fully retains its ability to inhibit binding of IgG or IgA antibodies from patients with APS to beta-2-glycoprotein I in vitro. Arthritis Rheum. 2015;67:2177.

    Google Scholar 

  57. McDonnell T, Pericleous C, Ioannou Y, Giles I, Rahman A. The ability of recombinant domain I of beta-2-glycoprotein I to inhibit lupus anticoagulant effect of IgG from patients with APS is enhanced by PEGylation. Arthritis Rheum. 2015;67:2176.

    Article  CAS  Google Scholar 

  58. Hunt J, Krilis S. The fifth domain of beta 2-glycoprotein I contains a phospholipid binding site (Cys281-Cys288) and a region recognized by anticardiolipin antibodies. J Immunol. 1994;152:653–9.

    CAS  PubMed  Google Scholar 

  59. Ostertag MV, Liu X, Henderson V, Pierangeli SS. A peptide that mimics the Vth region of beta-2-glycoprotein I reverses antiphospholipid-mediated thrombosis in mice. Lupus. 2006;15:358–65.

    Article  CAS  PubMed  Google Scholar 

  60. de la Torre YM, Pregnolato F, D'Amelio F, et al. Anti-phospholipid induced murine fetal loss: novel protective effect of a peptide targeting the beta2 glycoprotein I phospholipid-binding site. Implications for human fetal loss. J Autoimmun. 2012;38:J209–15.

    Article  PubMed  CAS  Google Scholar 

  61. Blank M, Baraam L, Eisenstein M, et al. Beta2-glycoprotein-I based peptide regulate endothelial-cells tissue-factor expression via negative regulation of pGSK3beta expression and reduces experimental-antiphospholipid-syndrome. J Autoimmun. 2011;37:8–17.

    Article  CAS  PubMed  Google Scholar 

  62. Kolyada A, Lee CJ, De Biasio A, Beglova N. A novel dimeric inhibitor targeting Beta2GPI in Beta2GPI/antibody complexes implicated in antiphospholipid syndrome. PLoS One. 2010;5:e15345.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Kolyada A, Porter A, Beglova N. Inhibition of thrombotic properties of persistent autoimmune anti-beta2GPI antibodies in the mouse model of antiphospholipid syndrome. Blood. 2014;123:1090–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Kolyada A, Karageorgos I, Mahlawat P, Beglova N. An A1-A1 mutant with improved binding and inhibition of beta2GPI/antibody complexes in antiphospholipid syndrome. FEBS J. 2015;282:864–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Agmon-Levin N, Blank M, Zandman-Goddard G, et al. Vitamin D: an instrumental factor in the anti-phospholipid syndrome by inhibition of tissue factor expression. Ann Rheum Dis. 2011;70:145–50.

    Article  CAS  PubMed  Google Scholar 

  66. Andreoli L, Piantoni S, Dall'Ara F, Allegri F, Meroni PL, Tincani A. Vitamin D and antiphospholipid syndrome. Lupus. 2012;21:736–40.

    Article  CAS  PubMed  Google Scholar 

  67. Piantoni S, Andreoli L, Allegri F, Meroni PL, Tincani A. Low levels of vitamin D are common in primary antiphospholipid syndrome with thrombotic disease. Reumatismo. 2012;64:307–13.

    Article  CAS  PubMed  Google Scholar 

  68. Halhali A, Acker GM, Garabedian M. 1,25-dihydroxyvitamin D3 induces in vivo the decidualization of rat endometrial cells. J Reprod Fertil. 1991;91:59–64.

    Article  CAS  PubMed  Google Scholar 

  69. Stephanou A, Ross R, Handwerger S. Regulation of human placental lactogen expression by 1,25-dihydroxyvitamin D3. Endocrinology. 1994;135:2651–6.

    Article  CAS  PubMed  Google Scholar 

  70. Du H, Daftary GS, Lalwani SI, Taylor HS. Direct regulation of HOXA10 by 1,25-(OH)2D3 in human myelomonocytic cells and human endometrial stromal cells. Mol Endocrinol. 2005;19:2222–33.

    Article  CAS  PubMed  Google Scholar 

  71. Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, Roberts JM. Maternal vitamin D deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab. 2007;92:3517–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Ota K, Dambaeva S, Han AR, Beaman K, Gilman-Sachs A, Kwak-Kim J. Vitamin D deficiency may be a risk factor for recurrent pregnancy losses by increasing cellular immunity and autoimmunity. Hum Reprod. 2014;29:208–19.

    Article  CAS  PubMed  Google Scholar 

  73. Chaouat G. The Th1/Th2 paradigm: still important in pregnancy? Semin Immunopathol. 2007;29:95–113.

    Article  PubMed  Google Scholar 

  74. Gysler SM, Mulla MJ, Stuhlman M, et al. Vitamin D reverses aPL-induced inflammation and LMWH-induced sFlt-1 release by human trophoblast. Am J Reprod Immunol. 2015;73:242–50.

    Article  CAS  PubMed  Google Scholar 

  75. Han CS, Mulla MJ, Brosens JJ, et al. Aspirin and heparin effect on basal and antiphospholipid antibody modulation of trophoblast function. Obstet Gynecol. 2011;118:1021–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Carroll TY, Mulla MJ, Han CS, et al. Modulation of trophoblast angiogenic factor secretion by antiphospholipid antibodies is not reversed by heparin. Am J Reprod Immunol. 2011;66:286–96.

    Article  CAS  PubMed  Google Scholar 

  77. Rosenberg VA, Buhimschi IA, Lockwood CJ, et al. Heparin elevates circulating soluble fms-like tyrosine kinase-1 immunoreactivity in pregnant women receiving anticoagulation therapy. Circulation. 2011;124:2543–53.

    Article  CAS  PubMed  Google Scholar 

  78. Maynard SE, Min JY, Merchan J, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003;111:649–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. de Jesus GR, Rodrigues G, de Jesus NR, Levy RA. Pregnancy morbidity in antiphospholipid syndrome: what is the impact of treatment? Curr Rheumatol Rep. 2014;16:403.

    Article  PubMed  CAS  Google Scholar 

  80. Amigo MC, Garcia-Torres R, Robles M, Bochicchio T, Reyes PA. Renal involvement in primary antiphospholipid syndrome. J Rheumatol. 1992;19:1181–5.

    CAS  PubMed  Google Scholar 

  81. Hughson MD, McCarty GA, Brumback RA. Spectrum of vascular pathology affecting patients with the antiphospholipid syndrome. Hum Pathol. 1995;26:716–24.

    Article  CAS  PubMed  Google Scholar 

  82. Canaud G, Bienaimé F, Tabarin F, et al. Inhibition of the mTORC pathway in the antiphospholipid syndrome. N Engl J Med. 2014;371:303–12.

    Article  PubMed  CAS  Google Scholar 

  83. Lepin EJ, Zhang Q, Zhang X, et al. Phosphorylated S6 ribosomal protein: a novel biomarker of antibody-mediated rejection in heart allografts. Am J Transplant. 2006;6:1560–71.

    Article  CAS  PubMed  Google Scholar 

  84. Gallo R, Padurean A, Jayaraman T, et al. Inhibition of intimal thickening after balloon angioplasty in porcine coronary arteries by targeting regulators of the cell cycle. Circulation. 1999;99:2164–70.

    Article  CAS  PubMed  Google Scholar 

  85. Canaud G, Legendre C, Terzi F. AKT/mTORC pathway in antiphospholipid-related vasculopathy: a new player in the game. Lupus. 2015;24:227–30.

    Article  CAS  PubMed  Google Scholar 

  86. Canaud G, Bienaimé F, Viau A, et al. AKT2 is essential to maintain podocyte viability and function during chronic kidney disease. Nat Med. 2013;19:1288–96.

    Article  CAS  PubMed  Google Scholar 

  87. Berchtold D, Piccolis M, Chiaruttini N, et al. Plasma membrane stress induces relocalization of Slm proteins and activation of TORC2 to promote sphingolipid synthesis. Nat Cell Biol. 2012;14:542–7.

    Article  CAS  PubMed  Google Scholar 

  88. Cox D, Brennan M, Moran N. Integrins as therapeutic targets: lessons and opportunities. Nat Rev Drug Discov. 2010;9:804–20.

    Article  CAS  PubMed  Google Scholar 

  89. Bledzka K, Plow EF. Integrin αIIbβ3: from discovery to efficacious therapeutic target. Circ Res. 2013;112:1189–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. The EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Engl J Med. 1994;330:956–61.

    Article  Google Scholar 

  91. Three-year duration of benefit from abciximab in patients receiving stents for acute myocardial infarction in the randomized double-blind ADMIRAL study. Eur Heart J. 2005;26:2520–3.

    Google Scholar 

  92. Ndrepepa G, Kastrati A, Neumann FJ, Schmitt C, Mehilli J, Schomig A. Five-year outcome of patients with acute myocardial infarction enrolled in a randomised trial assessing the value of abciximab during coronary artery stenting. Eur Heart J. 2004;5:1635–40.

    Article  CAS  Google Scholar 

  93. Coster S, van Dijk LC, Treurniet FEE, van Overhagen H, van Woerkom TCAM. Successful intra-arterial thrombolysis beyond the accepted 6-hour time window in two young patients. J Neurol Sci. 2010;288:182–5.

    Article  PubMed  Google Scholar 

  94. Marti V, Seixo F, Santaló M, Serra A. Antiphospholipid syndrome and acute myocardial infarction: treatment with thrombectomy and abciximab. Rev Port Cardiol. 2014;33:7–8.

    Google Scholar 

  95. Saunders KH, Erkan D, Lockshin MD. Perioperative management of antiphospholipid antibody-positive patients. Curr Rheumatol Rep. 2014;16:426–34.

    Article  PubMed  CAS  Google Scholar 

  96. Schrör K, Weber A. Comparative pharmacology of GP IIb/IIIa antagonists. J Thromb Thrombolysis. 2003;15:71–80.

    Article  PubMed  Google Scholar 

  97. Pancioli AM, Adeoye O, Schmit PA, et al. Combined approach to lysis utilizing eptifibatide and recombinant tissue plasminogen activator in acute ischemic stroke-enhanced regimen stroke trial. Stroke. 2013;44:2381–7.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Adeoye O, Sucharew H, Khoury J, et al. Combined approach to lysis utilizing eptifibatide and recombinant tissue-type plasminogen activator in acute ischemic stroke-full dose regimen stroke trial. Stroke. 2015;46:2529–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Proulle V, Furie RA, Merrill-Skoloff G, Furie BC, Furie B. Platelets are required for enhanced activation of the endothelium and fibrinogen in a mouse thrombosis model of APS. Blood. 2014;124:611–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Mega JL, Simon T. Pharmacology of antithrombotic drugs: an assessment of oral antiplatelet and anticoagulant treatments. Lancet. 2015;386:281–91.

    Article  CAS  PubMed  Google Scholar 

  101. Franchi F, Rollini F, Park Y, Angiolillo DJ. Novel antiplatelet agents: the current state and what is coming down the pike. Prog Cardiovasc Dis. 2015;58:267–77.

    Article  PubMed  Google Scholar 

  102. In-Chul P, Yang-Hyun B, Sang-Young H, et al. Simultaneous intrahepatic and subgaleal hemorrhage in antiphospholipid syndrome following anticoagulation therapy. World J Gastroenterol. 2013;19:6494–9.

    Article  Google Scholar 

  103. Ascer E, Goldstein Ascer L, Gidlund M. A large and massive abdominal venous thrombosis associated with the presence of a big axillary mass, lupus-like syndrome and antiphospholipid antibodies. BMJ Case Reports. 2011; doi:10.1136/bcr.05.2011.4217.

    Google Scholar 

  104. Smukowska-Gorynia A, Mularek-Kubzdela T, Araszkiewicz A. Recurrent acute myocardial infarction as an initial manifestation of antiphospholipid syndrome: treatment and management. Blood Coagul Fibrinolysis. 2015;26:91–4.

    Article  CAS  PubMed  Google Scholar 

  105. Fujieda Y, Amengual O, Watanabe T, et al. Dual antiplatelet therapy as prophylaxis of recurrent arterial thrombosis in patients with antiphospholipid syndrome. Arthritis Rheum. 2012;64:S1036 (abstract).

    Google Scholar 

  106. Pescador R, Capuzzi L, Mantovani M, Fulgenzi A, Ferrero ME. Defibrotide: properties and clinical use of an old/new drug. Vasc Pharmacol. 2013;59:1–10.

    Article  CAS  Google Scholar 

  107. Morabito F, Gentile M, Gay F, et al. Insights into defibrotide: an updated review. Expert Opin Biol Ther. 2009;9:6,763–72.

    Article  PubMed  Google Scholar 

  108. Strouse C, Richardson P, Prentice G, et al. Defibrotide for treatment of severe veno-occlusive disease in pediatrics and adults: an exploratory analysis using data from the Center for International Blood and Marrow Transplant Research. Biol Blood Marrow Transplant. 2016;22:1306–12.

    Article  CAS  PubMed  Google Scholar 

  109. Burcoglu-O'Ral A, Erkan D, Asherson R. Treatment of catastrophic antiphospholipid syndrome with defibrotide, a proposed vascular endothelial cell modulator. J Rheumatol. 2002;29:2006–11.

    PubMed  Google Scholar 

  110. Faxon DP, Creager MA, Smith Jr SC, et al. Atherosclerotic vascular disease conference: executive summary: atherosclerotic vascular disease conference proceeding for healthcare professionals from a special writing group of the American Heart Association. Circulation. 2004;109:2595–604.

    Article  PubMed  Google Scholar 

  111. Schrör K. The pharmacology of cilostazol. Diabetes Obes Metab. 2002; 4(Suppl 2): S14–9.

    Google Scholar 

  112. Igawa T, Tani T, Chijiwa T, et al. Potentiation of anti-platelet aggregating activity of cilostazol with vascular endothelial cells. Thromb Res. 1990;57:617–23.

    Google Scholar 

  113. Liu JS, Chuang TJ, Chen JH, et al. Cilostazol attenuates the severity of peripheral arterial occlusive disease in patients with type 2 diabetes: the role of plasma soluble receptor for advanced glycation end-products. Endocrine. 2015;49:703–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Morrow DE, Braunwald E, Bonaca MP, et al. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med. 2012;366:1404–13.

    Article  CAS  PubMed  Google Scholar 

  115. De Caterina R, Goto S. Targeting thrombin long-term after an acute coronary syndrome. Opportunities and challenges. Vascul Pharmacol. 2016;81:1–14.

    Article  PubMed  CAS  Google Scholar 

  116. Espinosa G, Cervera R. Current treatment of antiphospholipid syndrome: lights and shadows. Nat Rev Rheumatol. 2015;11:586–96.

    Article  CAS  PubMed  Google Scholar 

  117. Tricoci P, Huang Z, Held C, et al. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med. 2012;5:20–33.

    Article  CAS  Google Scholar 

  118. Xie H, Zhou H, Wang H, Chen D, Xia L, Wang T, Yan J. Anti-β2GPI/β2GPI induced TF and TNF-α expression in monocytes involving both TLR4/MyD88 and TLR4/TRIF signaling pathways. Mol Immunol. 2013;53:246–54.

    Article  CAS  PubMed  Google Scholar 

  119. Vega-Ostertag M, Harris EN, Pierangeli SS. Intracellular events in platelet activation induced by antiphospholipid antibodies in the presence of low doses of thrombin. Arthritis Rheum. 2004;50:2911–9.

    Article  CAS  PubMed  Google Scholar 

  120. Vega-Ostertag M, Casper K, Swerlick R, Ferrara D, Harris EN, Pierangeli SS. Involvement of p38 MAPK in the up-regulation of tissue factor on endothelial cells by antiphospholipid antibodies. Arthritis Rheum. 2005;52:1545–54.

    Article  CAS  PubMed  Google Scholar 

  121. Montiel-Manzano G, Romay-Penabad Z, Papalardo de Martínez E, et al. In vivo effects of an inhibitor of nuclear factor-kappa B on thrombogenic properties of antiphospholipid antibodies. Ann N Y Acad Sci. 2007;1108:540–53.

    Article  CAS  PubMed  Google Scholar 

  122. Nishimura M, Nii T, Trimova G, et al. The NF-kB specific inhibitor DHMEQ prevents thrombus formation in a mouse model of antiphospholipid syndrome. J Nephropathol. 2013;2:114–21.

    Article  PubMed  PubMed Central  Google Scholar 

  123. Cugno M, Borghi MO, Lonati LM, et al. Patients with antiphospholipid syndrome display endothelial perturbation. J Autoimmun. 2010;34:105–10.

    Article  CAS  PubMed  Google Scholar 

  124. Zhou H. Dilazep and dipyridamole inhibit tissue factor expression on monocytes induced by IgG from patients with antiphospholipid syndrome. Acta Pharmacol Sin. 2004;25:1366–7.

    CAS  PubMed  Google Scholar 

  125. Napoleone E, Di Santo A, Camera M, Tremoli E, Lorenzet R. Angiotensin-converting enzyme inhibitors down regulate tissue factor synthesis in monocytes. Circ Res. 2000;86:139–43.

    Article  CAS  PubMed  Google Scholar 

  126. Saravanan PB, Shanmuganathan MV, Ramanathan M. Telmisartan attenuated LPS-induced neuroinflammation in human IMR-32 neuronal cell line via SARM in AT1R independent mechanism. Life Sci. 2015;130:88–96.

    Article  CAS  PubMed  Google Scholar 

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Andrade, D. et al. (2017). 15th International Congress on Antiphospholipid Antibodies Task Force on Antiphospholipid Syndrome Treatment Trends Report. In: Erkan, D., Lockshin, M. (eds) Antiphospholipid Syndrome. Springer, Cham. https://doi.org/10.1007/978-3-319-55442-6_18

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