rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2011-522rsp-660Research ArticleСтатьиArticlesАнтифосфолипидный синдром и система фибринолизаThe antiphospholipid syndrome and the fibrinolytic systemOstryakovaEkaterina ViktorovnaOstryakovaEkaterina Viktorovnakaterina.ostryakova@yandex.ruPatrushevL IPatrushevL I-РешетнякТ. М.ReshetnyakT M-201115122011496№6 (2011)5764Copyright © Ostryakova E.V., Patrushev L.I., Решетняк Т.М., 20112011Ostryakova E.V., Patrushev L.I., Решетняк Т.М.Ostryakova E.V., Patrushev L.I., Reshetnyak T.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/660References<div><p>Насонов Е.Л. Антифосфолипидный синдром. М.: Литтерра, 2004;440 с.</p><p>Ruiz-Irastorza G., Crowther M., Branch W., Khamashta M.A. Antiphospholipid syndrome. Lancet 2010;376:1498–509.</p><p>Mehdi A.A., Uthman I., KhamashtaM. Antiphospholipid syndrome: pathogenesis and a window of treatment opportunities in the future. Eur J Clin Invest 2010;40:451–64.</p><p>Myakis S., Lockshin M.D., Atsumi T. et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome. J Thromb Haemost 2006;4:295–306.</p><p>Oosting J.D., Derksen R.H., BobbinkI.W. et al. Antiphospholipid antibodies directed against a combination of phospholipids with prothrombin, protein C, or protein S: an explanation for their pathogenic mechanism? Blood 1993;81:2618–25.</p><p>Cariou R., Tobelem G., Bellucci S. et al. Effect of lupus anticoagulant on antithrombogenic properties of endothelial cells – inhibition of thrombomodulin-dependent protein C activation. Thromb Haemost 1988;60:54–8.</p><p>Marciniak E., Romond E.H. Impaired catalytic function of activated protein C: a new in vitro manifestation of lupus anticoagulant. Blood 1989;74:2426–32.</p><p>Borrell M., Sala N., de Castellarnau C. et al. Immunoglobulin fractions isolated from patients with antiphospholipid antibodies prevent the inactivation of factor Va by activated protein C on human endothelial cells. Thromb Haemost 1992;68:268–72.</p><p>Escolar G., Font J., Reverter J.C. et al. Plasma from systemic lupus erythematosus patients with antiphospholipid antibodies promotes platelet aggregation. Arterioscler Thromb 1992;12:196–200.</p><p>Vega-Ostertag M., Harris E.N., Pierangeli S.S. Intracellular events in platelet activation induced by antiphospholipid antibodies in the presence of low doses of thrombin. Arthr Rheum 2004;50:2911–9.</p><p>Kornberg A., Blank M., Kaufman S., Shoenfeld Y. Induction of tissue factor-like activity in monocytes by anti-cardiolipin antibodies. J Immunol 1994;153:1328–32.</p><p>Amengual O., Atsumi T., Khamashta M.A., Hughes G.R. The role of the tissue factor pathway in the hypercoagulable state in patients with the antiphospholipid syndrome. Thromb Haemost 1998;79:276–81.</p><p>Vega-Ostertag M., Casper K., SwerlickR. et al. Involvement of p38 MAPK in the up-regulation of tissue factor on endothelial cells by antiphospholipid antibodies. Arthr Rheum 2005;52:1545–54.</p><p>Holers V.M., Girardi G., Mo L. et al. Complement c3 activation is required for antiphospholipid antibody-induced fetal loss. J Exp Med 2002;195:211–20.</p><p>Pierangeli S.S., Girardi G., Vega-Ostertag M. et al. Requirement of activationof complement C3 and C5 for antiphospholipid antibody-mediated thrombophilia. Arthr Rheum 2005;52:2120–4.</p><p>Pierangeli S.S., Chen P.P., Raschi E. et al. Antiphospholipid antibodies and the antiphospholipid syndrome: pathogenic mechanisms. Semin Thromb Hemost 2008; 34:236–50.</p><p>Myö hä nen H., Vaheri A. Regulation and interactions in the activation of cell-associated plasminogen. Cell Mol Life Sci 2004;61:2840–58.</p><p>Chen P.P., Giles I. Antibodies to serine proteases in the antiphospholipid syndrome. Curr Rheumatol Rep 2010;12:45–52.</p><p>Lisman T., de Groot P.G., Meijers J.C.M., Rosendaal F.R. Reduced plasma fibrinolytic potential is a risk factor for venous thrombosis. Blood 2005;105:1102–5.</p><p>Smalberg J.H., Kruip M.J.H.A., JanssenH.L.A. et al. Hypercoagulability and hypofibrinolysis and risk of deep vein thrombosis and splanchnic vein thrombosis. Arterioscler Thromb Vasc Biol 2011;31:485–93.</p><p>Долгов В.В., Свирин П.В. Лабораторная диагностика нарушений гемостаза. Москва – Тверь: Триада, 2005;227 с.</p><p>Hoover-Plow J. Does plasmin have anticoagulant activity? Vasc Health Risk Manag 2010;6:199–205.</p><p>Cesarman-Maus G., HajjarK.A. Molecular mechanisms of fibrinolysis. Br J Haematol 2005;129:307–21.</p><p>Dassah M.A., Deora A.B., He K., Hajjar K.A. The endothelial cell annexin A2 system and vascular fibrinolysis. Gen Physiol Biophys 2009;28(SPEC): F20–F28.</p><p>Colman R.W. Activation of plasminogen by human plasma kallikrein. Biochem Biophys Res Commun 1968;35:273–9.</p><p>Goldsmith G.H., Saito H., RatnoffO.D. The activation of plasminogen by Hageman factor (factor XII) and Hageman factor fragments. J Clin Invest 1978;62:54–60.</p><p>Schaller J., Gerber S.S. The plasminantiplasmin system: structural and functional aspects. Cell Mol Life Sci 2011;68:785–801.</p><p>Scott R.W., Bergman B.L., Bajpai A. et al. Protease nexin: properties and a modified purification procedure. J Biol Chem 1985;260:7029–34.</p><p>Jankun J., Skrzypczak-Jankun E. Yin and yang of the plasminogen activator inhibitor. Pol Arch Med Wewn 2009;119:410–7.</p><p>De Taeye B., Smith L.H., VaughanD.E. Plasminogen activator inhibitor-1: a common denominator in obesity, diabetes and cardiovascular disease. Curr Opin Pharmacol 2005;5:149–54.</p><p>Patrushev L. Fibrinolytic Disorders. In: Encyclopedia of molecular mechanisms of disease. F. Lang (ed.). Springer 2009;657–9.</p><p>Giannakopoulos B., Passam F., Rahgozar S., Krilis S.A. Current concepts on the pathogenesis of the antiphospholipidsyndrome. Blood 2007;109:422–30.</p><p>Vega-Ostertag M., PierangeliS.S. Mechanisms of aPL-mediated thrombosis: effects of aPL on endothelium and platelets. Curr Rheumatol Rep 2007;9:190–7.</p><p>Pierangeli S.S., Chen P.P., GonzalezE.B. Antiphospholipid antibodies and the antiphospholipid syndrome: an update on treatment and pathogenic mechanisms. Curr Opin Hematol 2006;13:366–75.</p><p>Koike T., Bohgaki M., Amengual O., Atsumi T. Antiphospholipid antibodies: lessons from the bench. J Autoimmun 2007;28:129–33.</p><p>Puurunen M., Manninen V., Falosuo T., Vaarala O. Antibodies to prothrombin cross-react with plasminogen in patients developing myocardial infarction. Br J Haematol 1998;100:374–9.</p><p>Simmelink M.J.A., de Groot P.G., Derksen R.H.W.M. A study on association between antiprothrombin antibodies, antiplasminogen antibodies and thrombosis. J Thromb Haemost 2003;1:735–9.</p><p>Yang C.D., Hwang K.K., Yan W. et al. Identification of anti-plasmin antibodies in the antiphospholipid syndrome that inhibit degradation of fibrin. J Immunol 2004;172:5765–73.</p><p>Bu C., Li Z., Zhang C. et al. IgG antibodies to plasminogen and their relationship to IgG anti-β2-glycoprotein I antibodies and thrombosis. Clin Rheumatol 2008;27:171–8.</p><p>Ede K., Hwang K.-K., Wu C.-C. et al. Plasmin immunization preferentially induces IgG-anticardiolipin antibodies that are potentially prothrombotic in MRL/MpJ mice. Arthr Rheum 2009;60(10):3108–17.</p><p>Kolev K., Gombas J., Varadi B. et al. Immunoglobulin G from patients with antiphospholipid syndrome impairs the fibrin dissolution with plasmin. Thromb Haemost 2002;87:502–8.</p><p>Ieko M., Ichikawa K., Atsumi T. et al. Effects of beta2-glycoprotein I and monoclonal anticardiolipin antibodies on extrinsic fibrinolysis. Semin Thromb Hemost 2000;26:85–90.</p><p>Atsumi T., Khamashta M.A., Andujar C. et al. Elevated plasma lipoprotein(a) level and its association with impaired fibrinolysis in patients with antiphospholipid syndrome. J Rheumatol 1998;25:69–73.</p><p>Zhu M., Olee T., Le D.T. et al. Characterization of IgG monoclonal anti-cardiolipin/antib2GP1 antibodies from two patients with the anti-phospholipid syndrome reveals three species of antibodies. Br J Haematol 1999;105:102–9.</p><p>Cugno M., Cabibbe M., Galli M. et al. 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 2004; 103:2121–6.</p><p>Lu C.S., Horizon A.A., Hwang K.K. etal. Identification of polyclonal and monoclonal antibodies against tissue plasminogen activator in the antiphospholipid syndrome. Arthr Rheum 2005;52:4018–27.</p><p>Bates R.L., Payne S.J., Drury S.L. et al. The prevalence and clinical significance of autoantibodies to plasminogen activator inhibitor 1 in systemic lupus erythematosus. Lupus 2003;12:617–22.</p><p>Rescher U., Gerke V. Annexins – unique membrane binding proteins with diverse functions. J Cell Sci 2004;117:2631–9.</p><p>Rand J.H., Wu X.X., Quinn A.S., Taatjes D.J. Resistance to annexin A5 anticoagulant activity: a thrombogenic mechanism for the antiphospholipid syndrome. Lupus 2008;17(10):922–30.</p><p>Rand J.H., Wu X.X., Quinn A.S. et al. Hydroxychloroquine protects the annexin A5 anticoagulant shield from disruption by antiphospholipid antibodies: evidence for a novel effect for an old antimalarial drug. Blood 2010;115(11):2292–9.</p><p>Алекберова З.С., Кошелева Н.М., Александрова Е.Н. Антитела к аннексину-5 у беременных с системной красной волчанкой. Науч-практич ревматол 2007;4:31–4.</p><p>Kassam G., Choi K.-S., Ghuman J. et al. The role of annexin II tetramer in the activation of plasminogen. J Biol Chem 1998;273:4790–9.</p><p>Ao W., Zheng H., Chen X.W. et al. Antiannexin II antibody is associated withthrombosis and/or pregnancy morbidity in antiphospholipid syndrome and systemic lupus erythematosus with thrombosis. Rheumatol Int 2010 [Epub. ahead of print] doi: 10.1007/s00296-010-1379-4.</p><p>Cesarman-Maus G., Cantu-Brito C., Barinagarrementeria F. et al. Autoantibodies against the fibrinolytic receptor, annexin A2, in cerebral venous thrombosis. Stroke 2011;42:501–3.</p><p>Romay-Penabad Z., Montiel-Manzano M.G., Shilagard T. et al. AnnexinA2 is involved in antiphospholipid antibody-mediated pathogenic effects in vitro and in vivo. Blood 2009;114:3074–83.</p><p>Laat B. de, Mertens K., Groot P.G. de. Mechanisms of disease: antiphospholipid antibodies – from clinical association to pathologic mechanism. Nat Clin Pract Rheumatol 2008;4:192–9.</p><p>Agar C., van Os G., Mö rgelin M. et al. β2-Glycoprotein I can exist in 2 conformations: implications for our understanding of the antiphospholipid syndrome. Blood 2010;116:1336–43.</p><p>Groot P.G. de, Derksen R.H.W.M., Urbanus R.T. The role of LRP8 (ApoER2’) in the pathophysiology of the antiphospholipid syndrome. Lupus 2010;19:389–93.</p><p>Sikara M.P., Routsias J.G., SamiotakiM. et al. β2 Glycoprotein I (β2GPI) binds platelet factor 4 (PF4): implications for the pathogenesis of antiphospholipid syndrome. Blood 2010;115:713–23.</p><p>Vlachoyiannopoulos P.G., Routsias J.G. A novel mechanism of thrombosis in antiphospholipid antibody syndrome. J Autoimmun 2010;35:248–55.</p><p>Yasuda S., Atsumi T., Matsuura E. et al. Significance of valine/leucine247 polymorphism of β2-glycoprotein I in antiphospholipid syndrome: increased reactivity of antiβ2-glycoprotein I autoantibodies to the valine247 β2-glycoprotein I variant. Arthr Rheum 2005;52:212–8.</p><p>Shi T., Iverson G.M., Qi J.C. et al. β2Glycoprotein I binds factor XI and inhibits its activation by thrombin and factor XIIa: Loss of inhibition by clipped β2-glycoproteinI. Proc Natl Acad Sci (USA) 2004;101:3939–44.</p><p>Ohkura N., Hagihara Y., Yoshimura T. et al. Plasmin can reduce the function of human β2 glycoprotein I by cleaving domain V into a nicked form. Blood 1998;91:4173–9.</p><p>Yasuda S., Atsumi T., Ieko M., Koike T. β2-glycoprotein I, anti-β2-glycoprotein I, and fibrinolysis. Thromb Res 2004;114:461–5.</p><p>Bu C., Gao L., Xie W. et al. β2Glycoprotein I is a cofactor for t-PA-mediated plasminogen activation. Arthr Rheum 2009;60:559–68.</p><p>Zorio E., Gilabert-Estelles J., Espana F. et al. Fibrinolysis: the key to new pathogenetic mechanisms. Curr Med Chem 2008;15:923–9.</p></div><br /><div><p>Насонов Е.Л. Антифосфолипидный синдром. М.: Литтерра, 2004;440 с.</p><p>Ruiz-Irastorza G., Crowther M., Branch W., Khamashta M.A. Antiphospholipid syndrome. Lancet 2010;376:1498–509.</p><p>Mehdi A.A., Uthman I., KhamashtaM. Antiphospholipid syndrome: pathogenesis and a window of treatment opportunities in the future. Eur J Clin Invest 2010;40:451–64.</p><p>Myakis S., Lockshin M.D., Atsumi T. et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome. J Thromb Haemost 2006;4:295–306.</p><p>Oosting J.D., Derksen R.H., BobbinkI.W. et al. Antiphospholipid antibodies directed against a combination of phospholipids with prothrombin, protein C, or protein S: an explanation for their pathogenic mechanism? Blood 1993;81:2618–25.</p><p>Cariou R., Tobelem G., Bellucci S. et al. Effect of lupus anticoagulant on antithrombogenic properties of endothelial cells – inhibition of thrombomodulin-dependent protein C activation. Thromb Haemost 1988;60:54–8.</p><p>Marciniak E., Romond E.H. Impaired catalytic function of activated protein C: a new in vitro manifestation of lupus anticoagulant. Blood 1989;74:2426–32.</p><p>Borrell M., Sala N., de Castellarnau C. et al. Immunoglobulin fractions isolated from patients with antiphospholipid antibodies prevent the inactivation of factor Va by activated protein C on human endothelial cells. Thromb Haemost 1992;68:268–72.</p><p>Escolar G., Font J., Reverter J.C. et al. Plasma from systemic lupus erythematosus patients with antiphospholipid antibodies promotes platelet aggregation. Arterioscler Thromb 1992;12:196–200.</p><p>Vega-Ostertag M., Harris E.N., Pierangeli S.S. Intracellular events in platelet activation induced by antiphospholipid antibodies in the presence of low doses of thrombin. Arthr Rheum 2004;50:2911–9.</p><p>Kornberg A., Blank M., Kaufman S., Shoenfeld Y. Induction of tissue factor-like activity in monocytes by anti-cardiolipin antibodies. J Immunol 1994;153:1328–32.</p><p>Amengual O., Atsumi T., Khamashta M.A., Hughes G.R. The role of the tissue factor pathway in the hypercoagulable state in patients with the antiphospholipid syndrome. Thromb Haemost 1998;79:276–81.</p><p>Vega-Ostertag M., Casper K., SwerlickR. et al. Involvement of p38 MAPK in the up-regulation of tissue factor on endothelial cells by antiphospholipid antibodies. Arthr Rheum 2005;52:1545–54.</p><p>Holers V.M., Girardi G., Mo L. et al. Complement c3 activation is required for antiphospholipid antibody-induced fetal loss. J Exp Med 2002;195:211–20.</p><p>Pierangeli S.S., Girardi G., Vega-Ostertag M. et al. Requirement of activationof complement C3 and C5 for antiphospholipid antibody-mediated thrombophilia. Arthr Rheum 2005;52:2120–4.</p><p>Pierangeli S.S., Chen P.P., Raschi E. et al. Antiphospholipid antibodies and the antiphospholipid syndrome: pathogenic mechanisms. Semin Thromb Hemost 2008; 34:236–50.</p><p>Myö hä nen H., Vaheri A. Regulation and interactions in the activation of cell-associated plasminogen. Cell Mol Life Sci 2004;61:2840–58.</p><p>Chen P.P., Giles I. Antibodies to serine proteases in the antiphospholipid syndrome. Curr Rheumatol Rep 2010;12:45–52.</p><p>Lisman T., de Groot P.G., Meijers J.C.M., Rosendaal F.R. Reduced plasma fibrinolytic potential is a risk factor for venous thrombosis. Blood 2005;105:1102–5.</p><p>Smalberg J.H., Kruip M.J.H.A., JanssenH.L.A. et al. Hypercoagulability and hypofibrinolysis and risk of deep vein thrombosis and splanchnic vein thrombosis. Arterioscler Thromb Vasc Biol 2011;31:485–93.</p><p>Долгов В.В., Свирин П.В. Лабораторная диагностика нарушений гемостаза. Москва – Тверь: Триада, 2005;227 с.</p><p>Hoover-Plow J. Does plasmin have anticoagulant activity? Vasc Health Risk Manag 2010;6:199–205.</p><p>Cesarman-Maus G., HajjarK.A. Molecular mechanisms of fibrinolysis. Br J Haematol 2005;129:307–21.</p><p>Dassah M.A., Deora A.B., He K., Hajjar K.A. The endothelial cell annexin A2 system and vascular fibrinolysis. Gen Physiol Biophys 2009;28(SPEC): F20–F28.</p><p>Colman R.W. Activation of plasminogen by human plasma kallikrein. Biochem Biophys Res Commun 1968;35:273–9.</p><p>Goldsmith G.H., Saito H., RatnoffO.D. The activation of plasminogen by Hageman factor (factor XII) and Hageman factor fragments. J Clin Invest 1978;62:54–60.</p><p>Schaller J., Gerber S.S. The plasminantiplasmin system: structural and functional aspects. Cell Mol Life Sci 2011;68:785–801.</p><p>Scott R.W., Bergman B.L., Bajpai A. et al. Protease nexin: properties and a modified purification procedure. J Biol Chem 1985;260:7029–34.</p><p>Jankun J., Skrzypczak-Jankun E. Yin and yang of the plasminogen activator inhibitor. Pol Arch Med Wewn 2009;119:410–7.</p><p>De Taeye B., Smith L.H., VaughanD.E. Plasminogen activator inhibitor-1: a common denominator in obesity, diabetes and cardiovascular disease. Curr Opin Pharmacol 2005;5:149–54.</p><p>Patrushev L. Fibrinolytic Disorders. In: Encyclopedia of molecular mechanisms of disease. F. Lang (ed.). Springer 2009;657–9.</p><p>Giannakopoulos B., Passam F., Rahgozar S., Krilis S.A. Current concepts on the pathogenesis of the antiphospholipidsyndrome. Blood 2007;109:422–30.</p><p>Vega-Ostertag M., PierangeliS.S. Mechanisms of aPL-mediated thrombosis: effects of aPL on endothelium and platelets. Curr Rheumatol Rep 2007;9:190–7.</p><p>Pierangeli S.S., Chen P.P., GonzalezE.B. Antiphospholipid antibodies and the antiphospholipid syndrome: an update on treatment and pathogenic mechanisms. Curr Opin Hematol 2006;13:366–75.</p><p>Koike T., Bohgaki M., Amengual O., Atsumi T. Antiphospholipid antibodies: lessons from the bench. J Autoimmun 2007;28:129–33.</p><p>Puurunen M., Manninen V., Falosuo T., Vaarala O. Antibodies to prothrombin cross-react with plasminogen in patients developing myocardial infarction. Br J Haematol 1998;100:374–9.</p><p>Simmelink M.J.A., de Groot P.G., Derksen R.H.W.M. A study on association between antiprothrombin antibodies, antiplasminogen antibodies and thrombosis. J Thromb Haemost 2003;1:735–9.</p><p>Yang C.D., Hwang K.K., Yan W. et al. Identification of anti-plasmin antibodies in the antiphospholipid syndrome that inhibit degradation of fibrin. J Immunol 2004;172:5765–73.</p><p>Bu C., Li Z., Zhang C. et al. IgG antibodies to plasminogen and their relationship to IgG anti-β2-glycoprotein I antibodies and thrombosis. Clin Rheumatol 2008;27:171–8.</p><p>Ede K., Hwang K.-K., Wu C.-C. et al. Plasmin immunization preferentially induces IgG-anticardiolipin antibodies that are potentially prothrombotic in MRL/MpJ mice. Arthr Rheum 2009;60(10):3108–17.</p><p>Kolev K., Gombas J., Varadi B. et al. Immunoglobulin G from patients with antiphospholipid syndrome impairs the fibrin dissolution with plasmin. Thromb Haemost 2002;87:502–8.</p><p>Ieko M., Ichikawa K., Atsumi T. et al. Effects of beta2-glycoprotein I and monoclonal anticardiolipin antibodies on extrinsic fibrinolysis. Semin Thromb Hemost 2000;26:85–90.</p><p>Atsumi T., Khamashta M.A., Andujar C. et al. Elevated plasma lipoprotein(a) level and its association with impaired fibrinolysis in patients with antiphospholipid syndrome. J Rheumatol 1998;25:69–73.</p><p>Zhu M., Olee T., Le D.T. et al. Characterization of IgG monoclonal anti-cardiolipin/antib2GP1 antibodies from two patients with the anti-phospholipid syndrome reveals three species of antibodies. Br J Haematol 1999;105:102–9.</p><p>Cugno M., Cabibbe M., Galli M. et al. 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 2004; 103:2121–6.</p><p>Lu C.S., Horizon A.A., Hwang K.K. etal. Identification of polyclonal and monoclonal antibodies against tissue plasminogen activator in the antiphospholipid syndrome. Arthr Rheum 2005;52:4018–27.</p><p>Bates R.L., Payne S.J., Drury S.L. et al. The prevalence and clinical significance of autoantibodies to plasminogen activator inhibitor 1 in systemic lupus erythematosus. Lupus 2003;12:617–22.</p><p>Rescher U., Gerke V. Annexins – unique membrane binding proteins with diverse functions. J Cell Sci 2004;117:2631–9.</p><p>Rand J.H., Wu X.X., Quinn A.S., Taatjes D.J. Resistance to annexin A5 anticoagulant activity: a thrombogenic mechanism for the antiphospholipid syndrome. Lupus 2008;17(10):922–30.</p><p>Rand J.H., Wu X.X., Quinn A.S. et al. Hydroxychloroquine protects the annexin A5 anticoagulant shield from disruption by antiphospholipid antibodies: evidence for a novel effect for an old antimalarial drug. Blood 2010;115(11):2292–9.</p><p>Алекберова З.С., Кошелева Н.М., Александрова Е.Н. Антитела к аннексину-5 у беременных с системной красной волчанкой. Науч-практич ревматол 2007;4:31–4.</p><p>Kassam G., Choi K.-S., Ghuman J. et al. The role of annexin II tetramer in the activation of plasminogen. J Biol Chem 1998;273:4790–9.</p><p>Ao W., Zheng H., Chen X.W. et al. Antiannexin II antibody is associated withthrombosis and/or pregnancy morbidity in antiphospholipid syndrome and systemic lupus erythematosus with thrombosis. Rheumatol Int 2010 [Epub. ahead of print] doi: 10.1007/s00296-010-1379-4.</p><p>Cesarman-Maus G., Cantu-Brito C., Barinagarrementeria F. et al. Autoantibodies against the fibrinolytic receptor, annexin A2, in cerebral venous thrombosis. Stroke 2011;42:501–3.</p><p>Romay-Penabad Z., Montiel-Manzano M.G., Shilagard T. et al. AnnexinA2 is involved in antiphospholipid antibody-mediated pathogenic effects in vitro and in vivo. Blood 2009;114:3074–83.</p><p>Laat B. de, Mertens K., Groot P.G. de. Mechanisms of disease: antiphospholipid antibodies – from clinical association to pathologic mechanism. Nat Clin Pract Rheumatol 2008;4:192–9.</p><p>Agar C., van Os G., Mö rgelin M. et al. β2-Glycoprotein I can exist in 2 conformations: implications for our understanding of the antiphospholipid syndrome. Blood 2010;116:1336–43.</p><p>Groot P.G. de, Derksen R.H.W.M., Urbanus R.T. The role of LRP8 (ApoER2’) in the pathophysiology of the antiphospholipid syndrome. Lupus 2010;19:389–93.</p><p>Sikara M.P., Routsias J.G., SamiotakiM. et al. β2 Glycoprotein I (β2GPI) binds platelet factor 4 (PF4): implications for the pathogenesis of antiphospholipid syndrome. Blood 2010;115:713–23.</p><p>Vlachoyiannopoulos P.G., Routsias J.G. A novel mechanism of thrombosis in antiphospholipid antibody syndrome. J Autoimmun 2010;35:248–55.</p><p>Yasuda S., Atsumi T., Matsuura E. et al. Significance of valine/leucine247 polymorphism of β2-glycoprotein I in antiphospholipid syndrome: increased reactivity of antiβ2-glycoprotein I autoantibodies to the valine247 β2-glycoprotein I variant. Arthr Rheum 2005;52:212–8.</p><p>Shi T., Iverson G.M., Qi J.C. et al. β2Glycoprotein I binds factor XI and inhibits its activation by thrombin and factor XIIa: Loss of inhibition by clipped β2-glycoproteinI. Proc Natl Acad Sci (USA) 2004;101:3939–44.</p><p>Ohkura N., Hagihara Y., Yoshimura T. et al. Plasmin can reduce the function of human β2 glycoprotein I by cleaving domain V into a nicked form. Blood 1998;91:4173–9.</p><p>Yasuda S., Atsumi T., Ieko M., Koike T. β2-glycoprotein I, anti-β2-glycoprotein I, and fibrinolysis. Thromb Res 2004;114:461–5.</p><p>Bu C., Gao L., Xie W. et al. β2Glycoprotein I is a cofactor for t-PA-mediated plasminogen activation. Arthr Rheum 2009;60:559–68.</p><p>Zorio E., Gilabert-Estelles J., Espana F. et al. Fibrinolysis: the key to new pathogenetic mechanisms. Curr Med Chem 2008;15:923–9.</p></div><br />
The authors declare that there are no conflicts of interest present.