nach oben

Current Rheumatology Reports

Erschienen in:

01.03.2018 | Systemic Lupus Erythematosus (G Tsokos, Section Editor)

Update on Antiphospholipid Syndrome: Ten Topics in 2017

verfasst von: Ilaria Cavazzana, Laura Andreoli, Maarteen Limper, Franco Franceschini, Angela Tincani

Erschienen in: Current Rheumatology Reports | Ausgabe 3/2018

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

This review focuses on new clinical aspects of antiphospholipid syndrome (APS) in the last 5 years.

Recent Findings

The pathogenesis of APS is related to endothelial activation by mechanisms other than autoantibody-mediated massive coagulation. These include Toll-like receptors, the m-TORC pathway, and neutrophil activation, inducing an uncontrolled inflammatory cascade. Given these new pathogenetic hypotheses, the treatment of APS could be directed towards a fine balance between anticoagulation and immunomodulation. A hot topic is how to consider asymptomatic antiphospholipid (aPL) carriers, with or without systemic lupus erythematosus (SLE), during pregnancy, or during their life in general: to treat or not to treat? New findings on long-standing APS, regarding survival, comorbidities, and evolution in other autoimmune conditions, have become available, including new insights into aPL as potential risk factors for damage accrual in SLE and potential implications on neuropsychological involvement of children exposed to maternal aPL in utero.

Summary

This review summarizes recent findings on the management, treatment, and prevention of patients affected by APS or with aPL.

Allen KL, Fonseca FV, Betapudi V, Willard B, Zhang J, McCrae KR. A novel pathway for human endothelial cell activation by antiphospholipid/anti-β2 glycoprotein I antibodies. Blood. 2012;119:884–93.PubMedPubMedCentralCrossRef

Wu M, Barnard J, Kundu S, McCrae KR. A novel pathway of cellular activation mediated by antiphospholipid antibody-induced extracellular vesicles. J Thromb Haemost. 2015;13:1928–40.PubMedPubMedCentralCrossRef

Borghi MO, Raschi E, Grossi C, Chighizola CB, Meroni PL. Toll-like receptor 4 and β2 glycoprotein I interaction on endothelial cells. Lupus. 2014 Oct;23(12):1302–4.PubMedCrossRef

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

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.PubMedCrossRef

Dunoyer-Geindre S, de Moerloose P, Galve-de Rochemonteix B, Reber G, Kruithof EKO. NFκ B is an essential intermediate in the activation of endothelial cells by anti-β2-glycoprotein 1 antibodies. Thromb Haemost. 2002;88:851–7.PubMedCrossRef

• van den Hoogen LL, Fritsch-Stork RD, Versnel MA, Derksen RH, van Roon JA, Radstake TR. Monocyte type I interferon signature in antiphospholipid syndrome is related to proinflammatory monocyte subsets, hydroxychloroquine and statin use. Ann Rheum Dis. 2016;75:e81. The paper analyzes type I interferon signatures in patients with APS, associated with a deficit of reparative endothelial cell progenitors and endothelial damage. PubMedCrossRef

Urbanus RT, Derksen RH, de Groot PG. Platelets and the antiphospholipid syndrome. Lupus. 2008;17:888–94.PubMedCrossRef

• Meng H, Yalavarthi S, Kanthi Y, Mazza LF, Elfine MA, Luke CE, et al. Role of neutrophil extracellular traps in antiphospholipid antibody-mediated venous thrombosis. 2017;Arthritis Rheumatol, 69:655–67. This paper describes the role of activated neutrophils in APs in endothelial dysfunction and pathogenesis of thrombosis, by releasing neutrophil extracellular traps.

10.

Yalavarthi S, Gould TJ, Rao AN, Mazza LF, Morris LE, Nunez-Alvarez C, et al. Release of neutrophil extracellular traps by neutrophils stimulated with antiphospholipid antibodies: a newly identified mechanism of thrombosis in the antiphospholipid syndrome. Arthritis Rheumatol. 2015;67:2990–3003.PubMedPubMedCentralCrossRef

11.

Knight JS, Meng H, Coit P, Yalavarthi S, Sule G, Gandhi AA, et al. Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target. JCI Insight. 2017;21:2(18).

12.

Mulla MJ, Brosens JJ, Chamley LW, Giles I, Pericleous C, Rahman A, et al. Antiphospholipid antibodies induce a pro-inflammatory response in first trimester trophoblast via the TLR4/MyD88 pathway. Am J Reprod Immunol. 2009;62:96–111.PubMedPubMedCentralCrossRef

13.

Ulrich V, Gelber SE, Vukelic M, Sacharidou A, Herz J, Urbanus RT, et al. ApoE receptor 2 mediation of trophoblast dysfunction and pregnancy complications induced by antiphospholipid antibodies in mice. Arthritis Rheum. 2016;68:730–9.CrossRef

14.

Marchetti T, Ruffatti A, Wuillemin C, de Moerloose P, Cohen M. Hydroxychloroquine restores trophoblast fusion affected by antiphospholipid antibodies. J Thromb Haemost. 2014;12:910–20.PubMedCrossRef

15.

Marder W, Knight JS, Kaplan MJ, Somers EC, Zhang X, O'Dell AA, et al. Placental histology and neutrophil extracellular traps in lupus and pre-eclampsia pregnancies. Lupus Sci Med. 2016;3:e000134.PubMedPubMedCentralCrossRef

16.

Girardi G, Berman J, Redecha P, Spruce L, Thurman JM, Kraus D, et al. Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. J Clin Invest. 2003;112:1644–54.PubMedPubMedCentralCrossRef

17.

Abrahams VM, Chamley LW, Salmon JE. Emerging treatment models in rheumatology: antiphospholipid syndrome and pregnancy: pathogenesis to translation. Arthritis Rheum. 2017;69:1710–21.CrossRef

18.

Bertolaccini ML, Amengual O, Andreoli L, Atsumi T, Chighizola CB, Forastiero R, et al. 14th International Congress on Antiphospholipid Antibodies Task Force. Report on antiphospholipid syndrome laboratory diagnostics and trends. Autoimmun Rev. 2014;13:917–30.PubMedCrossRef

19.

Chighizola CB, Gerosa M, Meroni PL. New tests to detect antiphospholipid antibodies: anti-domain I beta-2-glycoprotein-I antibodies. Curr Rheumatol Rep. 2014;16:402.PubMedCrossRef

20.

Pengo V, Ruffatti A, Tonello M, Cuffaro S, Banzato A, Bison E, et al. Antiphospholipid syndrome: antibodies to domain 1 of beta2-glycoprotein 1 correctly classify patients at risk. J Thromb Haemost. 2015;13:782–7.PubMedCrossRef

21.

Meneghel L, Ruffatti A, Gavasso S, Tonello M, Mattia E, Spiezia L, et al. Detection of IgG anti-domain I beta2 glycoprotein I antibodies by chemiluminescence immunoassay in primary antiphospholipid syndrome. Clin Chim Acta. 2015;446:201–5.PubMedCrossRef

22.

De Craemer AS, Musial J, Devreese KM. Role of anti-domain 1-beta2 glycoprotein I antibodies in the diagnosis and risk stratification of antiphospholipid syndrome. J Thromb Haemost. 2016;14:1779–87.PubMedCrossRef

23.

Andreoli L, Chighizola CB, Nalli C, Gerosa M, Borghi MO, Pregnolato F, et al. Clinical characterization of antiphospholipid syndrome by detection of IgG antibodies against beta-glycoprotein I domain 1 and domain 4/5: ratio of anti-domain 1 to anti-domain 4/5 as a useful new biomarker for antiphospholipid syndrome. Arthritis Rheum. 2015;67:2196–204.CrossRef

24.

Mondejar R, Gonzalez-Rodriguez C, Toyos-Saenz de Miera FJ, Melguizo-Madrid E, Zohoury N, Mahler M, et al. Role of antiphospholipid score and anti-beta2-glycoprotein I domain I autoantibodies in the diagnosis of antiphospholipid syndrome. Clin Chim Acta. 2014;431:174–8.PubMedCrossRef

25.

•• Radin M, Cecchi I, Roccatello D, Meroni PL, Sciascia S. Prevalence and thrombotic risk assessment of anti-beta2 glycoprotein I domain I antibodies: a systematic review. Seminars in thrombosis and hemostasis. 2017; https://doi.org/10.1055/s-0037-1603936. This review estimates the prevalence of anti-beta-2-GPI-domain I in patients with APS (analyzing 11 studies and 1585 patients), in order to determine whether anti--beta-2-GPI-domain I-positive individuals are at greater risk of thrombosis.

26.

Mahler M, Albesa R, Zohoury N, Bertolaccini ML, Ateka-Barrutia O, Rodriguez-Garcia JL, et al. Autoantibodies to domain 1 of beta 2 glycoprotein I determined using a novel chemiluminescence immunoassay demonstrate association with thrombosis in patients with antiphospholipid syndrome. Lupus. 2016;25:911–6.PubMedCrossRef

27.

Iwaniec T, Kaczor MP, Celinska-Lowenhoff M, Polanski S, Musial J. Clinical significance of anti-domain 1 beta2-glycoprotein I antibodies in antiphospholipid syndrome. Thromb Res. 2017;153:90–4.PubMedCrossRef

28.

Meneghel L, Ruffatti A, Gavasso S, Tonello M, Mattia E, Spiezia L, et al. The clinical performance of a chemiluminescent immunoassay in detecting anti-cardiolipin and anti-beta2 glycoprotein I antibodies. A comparison with a homemade ELISA method. Clin Chem Lab Med. 2015;53:1083–9.PubMedCrossRef

29.

Mattia E, Ruffatti A, Meneghel L, Tonello M, Faggian D, Hoxha A, et al. A contribution to detection of anticardiolipin and anti-beta2glycoprotein I antibodies: comparison between a home-made ELISA and a fluorescence enzyme immunoassay. Clinica Chimica Acta; Int J Clin Chem. 2015;446:93–6.CrossRef

30.

Devreese KM, Poncet A, Lindhoff-Last E, Musial J, de Moerloose P, Fontana P. A multicenter study to assess the reproducibility of antiphospholipid antibody results produced by an automated system. J Thromb Haemost. 2017;15:91–5.PubMedCrossRef

31.

Janek D, Slavik L, Ulehlova J, Krcova V, Hlusi A, Prochazkova J. Validation of a new panel of automated chemiluminescence assays for anticardiolipin antibodies in the screening for antiphospholipid syndrome. Clin Lab. 2016;62:1309–15.PubMedCrossRef

32.

Lakos G, Favaloro EJ, Harris EN, Meroni PL, Tincani A, Wong RC, et al. International consensus guidelines on anticardiolipin and anti-beta2-glycoprotein I testing: report from the 13th International Congress on antiphospholipid antibodies. Arthritis Rheum. 2012;64:1–10.PubMedCrossRef

33.

Iverson GM, Reddel S, Victoria EJ, Cockerill KA, Wang YX, Marti-Renom MA, et al. Use of single point mutations in domain I of beta 2-glycoprotein I to determine fine antigenic specificity of antiphospholipid autoantibodies. J Immunol. 2002;169:7097–103.PubMedCrossRef

34.

Shoenfeld Y, Krause I, Kvapil F, Sulkes J, Lev S, von Landenberg P, et al. Prevalence and clinical correlations of antibodies against six beta2-glycoprotein-I-related peptides in the antiphospholipid syndrome. J Clin Immunol. 2003;23:377–83.PubMedCrossRef

35.

de Laat B, Derksen RH, Urbanus RT, de Groot PG. IgG antibodies that recognize epitope Gly40-Arg43 in domain I of beta 2-glycoprotein I cause LAC, and their presence correlates strongly with thrombosis. Blood. 2005;105:1540–5.PubMedCrossRef

36.

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.PubMedPubMedCentralCrossRef

37.

Pozzi N, Banzato A, Bettin S, Bison E, Pengo V, De Filippis V. Chemical synthesis and characterization of wild-type and biotinylated N-terminal domain 1-64 of beta2-glycoprotein I. Protein Sci: a Publication Protein Soc. 2010;19:1065–78.CrossRef

38.

Banzato A, Pozzi N, Frasson R, De Filippis V, Ruffatti A, Bison E, et al. Antibodies to domain I of beta(2)glycoprotein I are in close relation to patients risk categories in antiphospholipid syndrome (APS). Thromb Res. 2011;128:583–6.PubMedCrossRef

39.

Mahler M, Norman GL, Meroni PL, Khamashta M. Autoantibodies to domain 1 of beta 2 glycoprotein 1: a promising candidate biomarker for risk management in antiphospholipid syndrome. Autoimmun Rev. 2012;12:313–7.PubMedCrossRef

40.

Roggenbuck D, Borghi MO, Somma V, Büttner T, Schierack P, Hanack K, et al. Antiphospholipid antibodies detected by line immunoassay differentiate among patients with antiphospholipid syndrome, with infections and asymptomatic carriers. Arthritis Res Ther. 2016;18:111.PubMedPubMedCentralCrossRef

41.

Roggenbuck D, Somma V, Schierack P, Borghi MO, Meroni PL. Autoantibody profiling in APS. Lupus. 2014;23:1262–4.PubMedCrossRef

42.

Ruiz-Irastorza G, Cuadrado MJ, Ruiz-Arruza I, Brey R, Crowther M, Derksen R, et al. Evidence-based recommendations for the prevention and long-term management of thrombosis in antiphospholipid antibody-positive patients: report of a task force at the 13th International Congress on antiphospholipid antibodies. Lupus. 2011;20:206–18.PubMedCrossRef

43.

Ruiz-Irastorza G, Hunt BJ, Khamashta MA. A systematic review of secondary thromboprophylaxis in patients with antiphospholipid antibodies. Arthritis Rheum. 2007;57:1487–95.PubMedCrossRef

44.

Erkan D, Patel S, Nuzzo M, Gerosa M, Meroni PL, Tincani A, et al. Management of the controversial aspects of the antiphospholipid syndrome pregnancies: a guide for clinicians and researchers. Rheumatology (Oxford). 2008;47(Suppl 3):iii23–7.

45.

Tincani A, Branch W, Levy RA, Piette JC, Carp H, Rai RS, et al. Treatment of pregnant patients with antiphospholipid syndrome. Lupus. 2003;12:524–9.PubMedCrossRef

46.

Østensen M, Khamashta M, Lockshin M, Parke A, Brucato A, Carp H, et al. Anti-inflammatory and immunosuppressive drugs and reproduction. Arthritis Res Ther. 2006;8:209.PubMedPubMedCentralCrossRef

47.

Ceccarelli F, Chighizola C, Finazzi G, Meroni PL, Valesini G. Thromboprophylaxis in carriers of antiphospholipid antibodies (APL) without previous thrombosis: “pros” and “cons”. Autoimmun Rev. 2012;11:568–71.PubMedCrossRef

48.

Reggia R, Andreoli L, Tincani A, Shoenfeld Y. Current treatment strategies for management of antiphospholipid syndrome. Expert Opin Orphan Drugs. 2014;2:1–11.

49.

Erkan D, Harrison MJ, Levy R, Peterson M, Petri M, Sammaritano L, et al. Aspirin for primary thrombosis prevention in the antiphospholipid syndrome: a randomized, double-blind, placebo-controlled trial in asymptomatic antiphospholipid antibody-positive individuals. Arthritis Rheum. 2007;56:2382–91.PubMedCrossRef

50.

• Erkan D, Unlu O, Sciascia S, Belmont HM, Branch DW, Cuadrado MJ, et al. Hydroxychloroquine in the primary thrombosis prophylaxis of antiphospholipid antibody positive patients without systemic autoimmune disease. Lupus. 2017, 1:961203317724219. https://doi.org/10.1177/0961203317724219. This is a randomized clinical trial focused on the efficacy of hydroxychloroquine in the primary thrombosis prevention of antiphospholipid antibody (aPL)-positive patients with no other systemic autoimmune diseases.

51.

• Nuri E, Taraborelli M, Andreoli L, Tonello M, Gerosa M, Calligaro A. Long-term use of hydroxychloroquine reduces antiphospholipid antibodies levels in patients with primary antiphospholipid syndrome. Immunol Res. 2017;65:17–24. This study shows a strong reduction in aPL titers and a decrease in the incidence of arterial thrombosis recurrence in PAPS patients treated with HCQ. PubMedCrossRef

52.

Kahlenberg JM, Kaplan MJ. The interplay of inflammation and cardiovascular disease in systemic lupus erythematosus. Arthritis Res Ther. 2011;13:203.PubMedPubMedCentralCrossRef

53.

Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis. 2010;69:20–8.PubMedCrossRef

54.

Wahl DG, Bounameaux H, de Moerloose P, Sarasin FP. Prophylactic antithrombotic therapy for patients with or without antiphospholipid antibodies: do the benefit outweigh the risk? A decision analysis. Arch Intern Med. 2000;160:2042–8.PubMedCrossRef

55.

Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, et al. Reduction in C-reactive proteinand LDL cholesterol and cardiovascularevent rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet. 2009;373:1175–82.PubMedCrossRef

56.

Jajoria P, Murthy V, Papalardo E, Romay-Penabad Z, Gleason C, Pierangeli SS. Statins for the treatment of antiphospholipid syndrome? Ann N Y Acad Sci. 2009;1173:736–45.PubMedCrossRef

57.

Agmon-Levin N, Blank M, Zandman-Goddard G, Orbach H, Meroni PL, Tincani A, et al. Vitamin D: an instrumental factor in the antiphospholipid syndrome by inhibition of tissue factor expression. Ann Rheum Dis. 2011;70:145–50.PubMedCrossRef

58.

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.PubMedCrossRef

59.

Soh MC, Pasupathy D, Gray G, Nelson-Piercy C. Persistent antiphospholipid antibodies do not contribute to adverse pregnancy outcomes. Rheumatology. 2013;52:1642–7.PubMedPubMedCentralCrossRef

60.

Wilson WA, Gharavi AE, Koike T, Lockshin MD, Branch DW, Piette J-C, et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: re-port of an international workshop. Arthritis Rheum. 1999;42:1309–11.PubMedCrossRef

61.

Fishman P, Falach-Vaknine E, Zigelman R, Bakimer R, Sredni B, Djaldetti M, et al. Prevention of fetal loss in experimental antiphospholipid syndrome by in vivo administration of recombinant interleukin-3. J Clin Invest. 1993;91:1834–7.PubMedPubMedCentralCrossRef

62.

Atallah A, Lecarpentier E, Goffinet F, Doret-Dion M, Gaucherand P, Tsatsaris V. Aspirin for prevention of preeclampsia. Drugs. 2017 Oct 16; https://doi.org/10.1007/s40265-017-0823-0.

63.

• 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. This is a multicenter, randomized, open-label trial evaluating rivaroxaban versus warfarin for the prevention of thromboembolic events, major bleeding and death in triple-positive patients with antiphospholipid syndrome. PubMedCrossRef

64.

Broder A, Putterman C. Hydroxychloroquine use is associated with lower odds of persistently positive antiphospholipid antibodies and/or lupus anticoagulant in systemic lupus erythematosus. J Rheumatol. 2013;40:30–3.PubMedCrossRef

65.

Krause I, Blank M, Kopolovic J, Afek A, Goldberg I, Tomer Y, et al. Abrogation of experimental systemic lupus erythematosus and primary antiphospholipid syndrome with intravenous gamma globulin. J Rheumatol. 1995;22:1068–74.PubMed

66.

Tenti S, Guidelli GM, Bellisai F, Galeazzi M, Fioravanti A. Long-term treatment of antiphospholipid syndrome with intravenous immunoglobulin in addition to conventional therapy. Clin Exp Rheumatol. 2013;31:877–82.PubMed

67.

Emmi G, Urban ML, Scalera A, Becatti M, Fiorillo C, Silvestri E, et al. Repeated low-dose courses of rituximab in SLE-associated antiphospholipid syndrome: data from a tertiary dedicated centre. Semin Arthritis Rheum. 2017;46:e21–3.PubMedCrossRef

68.

Wang CR, Liu MF. Rituximab usage in systemic lupus erythematosus-associated antiphospholipid syndrome: a single-center experience. Semin Arthritis Rheum. 2016;46:102–8.PubMedCrossRef

69.

Erkan D, Vega J, Ramón G, Kozora E, Lockshin MD. A pilot open-label phase II trial of rituximab for non-criteria manifestations of antiphospholipid syndrome. Arthritis Rheum. 2013;65:464–71.PubMedCrossRef

70.

• Leone A, Radin M, Almarzooqi AM, Al-Saleh J, Roccatello D, Sciascia S, et al. Autologous hematopoietic stem cell transplantation in Systemic Lupus Erythematosus and antiphospholipid syndrome: A systematic review. Autoimmun Rev. 2017;16:469–77. This review considered 25 studies (including 279 SLE patients and 54 cases with APS) analyzing the efficacy of HSCT: aPL negativization was reported in 9% in the APS patients and 73% of APS were able to discontinue anticoagulation after HSC. PubMedCrossRef

71.

Hadaya K, Ferrari-Lacraz S, Fumeaux D, Boehlen F, Toso C, Moll S, et al. Eculizumab in acute recurrence of thrombotic microangiopathy after renal transplantation. Am J Transplant. 2011;11:2523–7.PubMedCrossRef

72.

Kronbichler A, Frank R, Kirschfink M, Szilágyi Á, Csuka D, Prohászka Z, et al. Efficacy of eculizumab in a patient with immunoadsorption-dependent catastrophic antiphospholipid syndrome: a case report. Medicine (Baltimore). 2014;93:e143.CrossRef

73.

de Holanda MI, Pôrto LC, Wagner T, Christiani LF, Palma LMP. Use of eculizumab in a systemic lupus erythemathosus patient presenting thrombotic microangiopathy and heterozygous deletion in CFHR1-CFHR3. A case report and systematic review. Clin Rheumatol. 2017; https://doi.org/10.1007/s10067-017-3823-2.

74.

Zhou H, Sheng L, Wang H, Xie H, Mu Y, Wang T, et al. Anti-β2GPI/β2GPI stimulates activation of THP-1 cells through TLR4/MD-2/MyD88 and NF-κB signaling pathways. Thromb Res. 2013;132:742–9.PubMedCrossRef

75.

Hamid C, Norgate K, D'Cruz DP, Khamashta MA, Arno M, Pearson JD, et al. Anti-beta2GPI-antibody-induced endothelial cell gene expression profiling reveals induction of novel pro-inflammatory genes potentially involved in primary antiphospholipid syndrome. Ann Rheum Dis. 2007;66:1000–7.PubMedPubMedCentralCrossRef

76.

Xia L, Zhou H, Hu L, Xie H, Wang T, Xu Y, et al. Both NF-κB and c-Jun/AP-1 involved in anti-β2GPI/β2GPI-induced tissue factor expression in monocytes. Thromb Haemost. 2013;109:643–51.PubMedCrossRef

77.

Zhou H, Chen D, Xie H, Xia L, Wang T, Yuan W, et al. Activation of MAPKs in the anti-β2GPI/β2GPI-induced tissue factor expression through TLR4/IRAKs pathway in THP-1 cells. Thromb Res. 2012;130:e229–35.PubMedCrossRef

78.

Xia L, Zhou H, Wang T, Xie Y, Wang T, Wang X, et al. Activation of mTOR is involved in anti-β2GPI/β2GPI-induced expression of tissue factor and IL-8 in monocytes. Thromb Res. 2017;157:103–10.PubMedCrossRef

79.

Mak A, Cheung MW, Cheak AA, Ho RC. Combination of heparin and aspirin is superior to aspirin alone in enhancing live births in patients with recurrent pregnancy loss and positive anti-phospholipid antibodies: a meta-analysis of randomized controlled trials and meta-regression. Rheumatology (Oxford, England). 2010;49:281–8.CrossRef

80.

Ziakas PD, Pavlou M, Voulgarelis M. Heparin treatment in antiphospholipid syndrome with recurrent pregnancy loss: a systematic review and meta-analysis. Obstet Gynecol. 2010;115:1256–62.PubMedCrossRef

81.

de Jesus GR, Agmon-Levin N, Andrade CA, Andreoli L, Chighizola CB, Porter TF, et al. 14th International Congress on Antiphospholipid Antibodies Task Force report on obstetric antiphospholipid syndrome. Autoimmun Rev. 2014;13:795–813.PubMedCrossRef

82.

•• Andreoli L, Bertsias GK, Agmon-Levin N, Brown S, Cervera R, Costedoat-Chalumeau N, et al. EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann Rheum Dis. 2017;76:476–85. Recent European recommendations as guidelines for rheumatologists and gynecologists. PubMedPubMedCentralCrossRef

83.

Bramham K, Thomas M, Nelson-Piercy C, Khamashta M, Hunt J. First-trimester low-dose prednisolone in refractory antiphospholipid antibody-related pregnancy loss. Blood. 2011;117:6948–51.PubMedCrossRef

84.

Ruffatti A, Salvan E, Del Ross T, Gerosa M, Andreoli L, Maina A, et al. Treatment strategies and pregnancy outcomes in antiphospholipid syndrome patients with thrombosis and triple antiphospholipid positivity. A European multicentre retrospective study. Thromb Haemost. 2014;112:727–35.PubMedCrossRef

85.

Ruffatti A, Hoxha A, Favaro M, Tonello M, Colpo A, Cucchini U, et al. Additional treatments for high-risk obstetric antiphospholipid syndrome: a comprehensive review. Clin Rev Allergy Immunol. 2017;5:28–39.CrossRef

86.

Albert CR, Schlesinger WJ, Viall CA, Mulla MJ, Brosens JJ, Chamley LW, et al. Effect of hydroxychloroquine on antiphospholipid antibody-induced changes in first trimester trophoblast function. Am J Reprod Immunol (New York, NY : 1989). 2014;71:154–64.CrossRef

87.

Bertolaccini ML, Contento G, Lennen R, Sanna G, Blower PJ, Ma MT, et al. Complement inhibition by hydroxychloroquine prevents placental and fetal brain abnormalities in antiphospholipid syndrome. J Autoimmun. 2016;75:30–8.PubMedCrossRef

88.

Meroni PL. Prevention & treatment of obstetrical complications in APS: is hydroxychloroquine the holy grail we are looking for? J Autoimmun. 2016;75:1–5.PubMedCrossRef

89.

Mekinian A, Lazzaroni MG, Kuzenko A, Alijotas-Reig J, Ruffatti A, Levy P, et al. The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: data from a European multicenter retrospective study. Autoimmun Rev. 2015;14:498–502.PubMedCrossRef

90.

Sciascia S, Branch DW, Levy RA, Middeldorp S, Pavord S, Roccatello D, et al. The efficacy of hydroxychloroquine in altering pregnancy outcome in women with antiphospholipid antibodies. Evidence and clinical judgment. Thromb Haemost. 2016;115:285–90.PubMedCrossRef

91.

Mekinian A, Alijotas-Reig J, Carrat F, Costedoat-Chalumeau N, Ruffatti A, Lazzaroni MG, et al. Refractory obstetrical antiphospholipid syndrome: features, treatment and outcome in a European multicenter retrospective study. Autoimmun Rev. 2017;16:730–4.PubMedCrossRef

92.

Schreiber K, Breen K, Cohen H, Jacobsen S, Middeldorp S, Pavord S, et al. HYdroxychloroquine to Improve Pregnancy Outcome in Women with AnTIphospholipid Antibodies (HYPATIA) protocol: a multinational randomized controlled trial of hydroxychloroquine versus placebo in addition to standard treatment in pregnant women with antiphospholipid syndrome or antibodies. Semin Thromb Hemost. 2017;43:562–71.PubMedCrossRef

93.

Gotestam Skorpen C, Hoeltzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 2016;75:795–810.PubMedCrossRef

94.

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.PubMedPubMedCentralCrossRef

95.

Gelber SE, Brent E, Redecha P, Perino G, Tomlinson S, Davisson RL, et al. Prevention of defective placentation and pregnancy loss by blocking innate immune pathways in a syngeneic model of placental insufficiency. J Immunol (Baltimore, Md : 1950). 2015;195:1129–38.CrossRef

96.

Gustavsen A, Skattum L, Bergseth G, Lorentzen B, Floisand Y, Bosnes V, et al. Effect on mother and child of eculizumab given before caesarean section in a patient with severe antiphospholipid syndrome: a case report. Medicine. 2017;96:e6338.PubMedPubMedCentralCrossRef

97.

Kelly RJ, Hochsmann B, Szer J, Kulasekararaj A, de Guibert S, Roth A, et al. Eculizumab in pregnant patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2015;373:1032–9.PubMedCrossRef

98.

Di Simone N, D'Ippolito S, Marana R, Di Nicuolo F, Castellani R, Pierangeli SS, et al. Antiphospholipid antibodies affect human endometrial angiogenesis: protective effect of a synthetic peptide (TIFI) mimicking the phospholipid binding site of beta(2) glycoprotein I. Am J Reprod Immunol (New York, NY : 1989). 2013;70:299–308.CrossRef

99.

Agostinis C, Durigutto P, Sblattero D, Borghi MO, Grossi C, Guida F, et al. A non-complement-fixing antibody to beta2 glycoprotein I as a novel therapy for antiphospholipid syndrome. Blood. 2014;123:3478–87.PubMedCrossRef

100.

Mineo C, Lanier L, Jung E, Sengupta S, Ulrich V, Sacharidou A, et al. Identification of a monoclonal antibody that attenuates antiphospholipid syndrome-related pregnancy complications and thrombosis. PLoS One. 2016;11:e0158757.PubMedPubMedCentralCrossRef

101.

Zandman-Goddard G, Pierangeli SS, Gertel S, Blank M. Tolerogenic dendritic cells specific for beta2-glycoprotein-I domain-I, attenuate experimental antiphospholipid syndrome. J Autoimmun. 2014;54:72–80.PubMedCrossRef

102.

Bouvier S, Cochery-Nouvellon E, Lavigne-Lissalde G, Mercier E, Marchetti T, Balducchi JP, et al. Comparative incidence of pregnancy outcomes in treated obstetric antiphospholipid syndrome: the NOH-APS observational study. Blood. 2014;123:404–13.PubMedCrossRef

103.

Jeremic K, Stefanovic A, Dotlic J, Stojnic J, Kadija S, Vilendecic Z, et al. Neonatal outcome in pregnant patients with antiphospholipid syndrome. J Perinat Med. 2015;43:761–8.PubMedCrossRef

104.

Giron-Gonzalez JA, Garcia del Rio E, Rodriguez C, Rodriguez-Martorell J, Serrano A. Antiphospholipid syndrome and asymptomatic carriers of antiphospholipid antibody: prospective analysis of 404 individuals. J Rheumatol 2004;31:1560–1567.

105.

Bramham K, Hunt BJ, Germain S, Calatayud I, Khamashta M, Bewley S, et al. Pregnancy outcome in different clinical phenotypes of antiphospholipid syndrome. Lupus. 2010;19:58–64.PubMedCrossRef

106.

Ruffatti A, Tonello M, Visentin MS, Bontadi A, Hoxha A, De Carolis S, et al. Risk factors for pregnancy failure in patients with anti-phospholipid syndrome treated with conventional therapies: a multicentre, case-control study. Rheumatology (Oxford, England). 2011;50:1684–9.CrossRef

107.

Fischer-Betz R, Specker C, Brinks R, Schneider M. Pregnancy outcome in patients with antiphospholipid syndrome after cerebral ischaemic events: an observational study. Lupus. 2012;21:1183–9.PubMedCrossRef

108.

Danowski A, de Azevedo MN, de Souza Papi JA, Petri M. Determinants of risk for venous and arterial thrombosis in primary antiphospholipid syndrome and in antiphospholipid syndrome with systemic lupus erythematosus. J Rheumatol. 2009;36:1195–9.PubMedCrossRef

109.

Lockshin MD, Kim M, Laskin CA, Guerra M, Branch DW, Merrill J, et al. Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies. Arthritis Rheum. 2012;64:2311–8.PubMedPubMedCentralCrossRef

110.

Yelnik CM, Laskin CA, Porter TF, Branch DW, Buyon JP, Guerra MM, et al. Lupus anticoagulant is the main predictor of adverse pregnancy outcomes in aPL-positive patients: validation of PROMISSE study results. Lupus Sci Med. 2016;3:e000131.PubMedPubMedCentralCrossRef

111.

Saccone G, Berghella V, Maruotti GM, Ghi T, Rizzo G, Simonazzi G, et al. Antiphospholipid antibody profile based obstetric outcomes of primary antiphospholipid syndrome: the PREGNANTS study. Am J Obstet Gynecol. 2017;216:525.e1-.e12.

112.

Simchen MJ, Dulitzki M, Rofe G, Shani H, Langevitz P, Schiff E, et al. High positive antibody titers and adverse pregnancy outcome in women with antiphospholipid syndrome. Acta Obstet Gynecol Scand. 2011;90:1428–33.PubMedCrossRef

113.

Matsuki Y, Atsumi T, Yamaguchi K, Hisano M, Arata N, Oku K, et al. Clinical features and pregnancy outcome in antiphospholipid syndrome patients with history of severe pregnancy complications. Mod Rheumatol / Jpn Rheum Assoc. 2015;25:215–8.CrossRef

114.

• Rodríguez-Pintó I, Moitinho M, Santacreu I, Shoenfeld Y, Erkan D, Espinosa G, et al. Catastrophic antiphospholipid syndrome (CAPS): Descriptive analysis of 500 patients from the International CAPS Registry. Autoimmun Rev. 2016;15:1120–4. Multicenter registry on 500 APS patients encountering 522 CAPS episodes: triggers, clinical presentation and mortality rate. PubMedCrossRef

115.

Asherson RA, Cervera R, Piette JC, Shoenfeld Y, Espinosa G, Petri MA, et al. Catastrophic antiphospholipid syndrome: clues to the pathogenesis from a series of 80 patients. Medicine (Baltimore). 2001;80:355–77.CrossRef

116.

Bucciarelli S, Espinosa G, Cervera R, Erkan D, Gómez-Puerta JA, Ramos-Casals M, et al. European Forum on Antiphospholipid Antibodies. Mortality in the catastrophic antiphospholipid syndrome: causes of death and prognostic factors in a series of 250 patients. Arthritis Rheum. 2006;54:2568–76.PubMedCrossRef

117.

Cervera R. 8th international congress on autoimmunity: new perspectives for refractory catastrophic antiphospholipid syndrome. Expert Rev Clin Immunol. 2012;8:617–9.PubMedCrossRef

118.

Bayraktar UD, Erkan D, Bucciarelli S, Espinosa G, Asherson R. Catastrophic Antiphospholipid Syndrome Project Group. The clinical spectrum of catastrophic antiphospholipid syndrome in the absence and presence of lupus. J Rheumatol. 2007;34:346–52.PubMed

119.

Berman H, Rodríguez-Pintó I, Cervera R, Morel N, Costedoat-Chalumeau N, Erkan D, et al. Catastrophic Antiphospholipid Syndrome (CAPS) Registry Project Group (European Forum on Antiphospholipid Antibodies). Rituximab use in the catastrophic antiphospholipid syndrome: descriptive analysis of the CAPS registry patients receiving rituximab. Autoimmun Rev. 2013;12:1085–90.PubMedCrossRef

120.

Rodríguez-Pintó I, Cervera R, Espinosa G. Rituximab and its therapeutic potential in catastrophic antiphospolipid syndrome. Ther Adv Musculoskelet Dis. 2015;7:26–30.PubMedPubMedCentralCrossRef

121.

Sukara G, Baresic M, Sentic M, Brcic L, Anic B. Catastrophic antiphospholipid syndrome associated with systemic lupus erythematosus treated with rituximab: case report and a review of the literature. Acta Reumatol Port. 2015;40:169–75.PubMed

122.

Rand JH, Wu XX, Wolgast LR, Lei V, Conway EM. A novel 2-stage approach that detects complement activation in patients with antiphospholipid antibody syndrome. Thromb Res. 2017;156:119–25.PubMedCrossRef

123.

Oku K, Amengual O, Hisada R, Ohmura K, Nakagawa I, Watanabe T, et al. Autoantibodies against a complement component 1 q subcomponent contribute to complement activation and recurrent thrombosis/pregnancy morbidity in anti-phospholipid syndrome. Rheumatology (Oxford). 2016;55:1403–11.CrossRef

124.

Grosso G, Vikerfors A, Woodhams B, Adam M, Bremme K, Holmström M, et al. Thrombin activatable fibrinolysis inhibitor (TAFI)—a possible link between coagulation and complement activation in the antiphospholipid syndrome (APS). Thromb Res 2017 24. pii: S0049–3848(17)30392–4.

125.

Shapira I, Andrade D, Allen SL, Salmon JE. Brief report: induction of sustained remission in recurrent catastrophic antiphospholipid syndrome via inhibition of terminal complement with eculizumab. Arthritis Rheum. 2012;64:2719–23.PubMedCrossRef

126.

Owaidah TM, Maghrabi K, Elkarouri MA, Al Mohareeb F, Al Harthi A, Al ZH. Successful treatment of a case of catastrophic antiphospholipid syndrome with autologous BMT: case report and review of literature. Bone Marrow Transplant. 2011;46:597–600.PubMedCrossRef

127.

Oka S, Ono K, Nohgawa M. Successful treatment of catastrophic antiphospholipid antibody syndrome associated with MALT lymphoma by autologous hematopoietic stem cell transplantation. Intern Med. 2017;56:1207–12.PubMedPubMedCentralCrossRef

128.

Eyraud A, Scouppe L, Barnetche T, Forcade E, Lazaro E, Duffau P, et al. Efficacy and safety of autologous haematopoietic stem cell transplantation in systemic sclerosis: a systematic review of literature. Br J Dermatol. 2017;14 https://doi.org/10.1111/bjd.15993.

129.

Grika EP, Ziakas PD, Zintzaras E, Moutsopoulos HM, Vlachoyiannopoulos PG. Morbidity, mortality, and organ damage in patients with antiphospholipid syndrome. J Rheumatol. 2012;39:516–23.PubMedCrossRef

130.

Cervera R, Serrano R, Pons-Estel GJ, Ceberio-Hualde L, Shoenfeld Y, de Ramon E, et al. Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis. 2015;74:1011–8.PubMedCrossRef

131.

• Taraborelli M, Reggia R, Dall'Ara F, Fredi M, Andreoli L, Gerosa M, et al. Longterm outcome of patients with primary antiphospholipid syndrome: a retrospective multicenter study. J Rheumatol. 2017;44:1165–72. Multicenter retrospective study with 115 APS patients with follow-up more than 18 years: clinical features, treatment and evolution. PubMedCrossRef

132.

Hernandez-Molina G, Espericueta-Arriola G, Cabral AR. The role of lupus anticoagulant and triple marker positivity as risk factors for rethrombosis in patients with primary antiphospholipid syndrome. Clin Exp Rheumatol. 2013;31:382–8.PubMed

133.

Bazzan M, Vaccarino A, Stella S, Sciascia S, Montaruli B, Bertero MT, et al. Patients with antiphosholipid syndrome and thrombotic recurrences: a real world observation (the Piedmont cohort study). Lupus. 2016;25:479–85.PubMedCrossRef

134.

Ruiz-Irastorza G, Egurbide MV, Ugalde J, et al. High impact of antiphospholipid syndrome on irreversible organ damage and survival of patients with systemic lupus erythematosus. Arch Intern Med. 2004;164:77–82.PubMedCrossRef

135.

Petri M, Purvey S, Fang H, Magder LS. Predictors of organ damage in systemic lupus erythematosus: the Hopkins lupus cohort. Arthritis Rheumatism. 2012;64:4021–8.PubMedPubMedCentralCrossRef

136.

Ruiz-Irastorza G, Egurbide MV, Martinez-Berriotxoa A, Ugalde J, Aguirre C. Antiphospholipid antibodies predict damage in patients with systemic lupus erythematosus. Lupus. 2004;13:900–5.PubMedCrossRef

137.

Gladmann DD, Urowitz MB, Rahaman P, Ibanez D, Tam LS. Accrual of organ damage over time in patients with systemic lupus erythematosus. J Rheumatol. 2003;30:1955–9.

138.

Chambers SA, Allen E, Rahman A, Isenberg D. Damage and mortality in a group of British patients with systemic lupus erythematosus followed up for over 10 years. Rheumatology (Oxford). 2009;48:673–5.CrossRef

139.

Estevez del Toro M, Chico Capote A, Hechavarria R, Jiménez Paneque R, Kokuina E. Damage in cuban patients with systemic lupus erythematosus. Relation with disease features. Rheumatol Clin. 2010;6:11–5.

140.

Becker-Merok A, Nossent HC. Damage accumulation in systemic lupus erythematosus and its relation to disease activity and mortality. J Rheumatol. 2006;33:1570–7.PubMed

141.

Nossent J, Kiss E, Rozman B, Pokorny G, Vlachoyiannopoulos P, Olesinska M, et al. Disease activity and damage accrual during the early disease course in a multinational inception cohort of patients with systemic lupus erythematosus. Lupus. 2010;19:949–56.PubMedCrossRef

142.

Alarcon GS, McGwin G Jr, Bastian HM, Roseman J, Lisse J, Fessler BJ, et al. Systemic lupus erythematosus in three ethnic groups. VII. Predictors of early mortality in LUMINA cohort. LUMINA study group. Arthritis Rheum. 2001;45:191–202.PubMedCrossRef

143.

Yee CS, Hussein H, Skan J, Bowman S, Situnayake D, Gordon C. Association of damage with autoantibody profile, age, race, sex and disease duration in systemic lupus erythematosus. Rheumatology. 2003;42:276–9.PubMedCrossRef

144.

Mok CC, Ho CT, Wong RW, Lau CS. Damage accrual in southern Chinese patients with systemic lupus erythematosus. J Rheumatol. 2003;30:1513–9.PubMed

145.

Bruce IN, O'Kneeffe AG, Farewell V, et al. Factors associated with damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. Ann Rheum Dis. 2015;74:1706–13.PubMedCrossRef

146.

• Taraborelli M, Leuenberger L, Lazzaroni MG, Martinazzi N, Zhang W, Franceschini F, et al. The contribution of antiphospholipid antibodies to organ damage in systemic lupus erythematosus. Lupus. 2016;25:1365–8. The paper analyses whether a clinically significant aPL profile is associated with an increased risk of organ damage accrual during a 15-year follow-up in a cohort of 262 SLE. PubMedCrossRef

147.

Conti F, Ceccarelli F, Perricone C, Leccese I, Massaro L, Pacucci VA, et al. The chronic damage in systemic lupus erythematosus is driven by flares, glucocorticoids and antiphospholipid antibodies: results from a monocentric cohort. Lupus. 2016;25:719–26.PubMedCrossRef

148.

Taraborelli M, Cavazzana I, Martinazzi N, Lazzaroni MG, Fredi M, Andreoli L, et al. Organ damage accrual and distribution in systemic lupus erythematosus patients followed-up for more than 10 years. Lupus. 2017;26:1197–204.PubMedCrossRef

149.

Muscal E, Brey RL. Antiphospholipid syndrome and the brain in pediatric and adult patients. Lupus. 2010;19:406–11.PubMedPubMedCentralCrossRef

150.

Meroni PL, Raschi E, Testoni C, Borghi MO. Endothelial cell activation by antiphospholipid antibodies. Clin Immunol Orl Fla. 2004;112:169–74.CrossRef

151.

Branch DW, Dudley DJ, Mitchell MD, Creighton KA, Abbott TM, Hammond EH, et al. Immunoglobulin G fractions from patients with antiphospholipid antibodies cause fetal death in BALB/c mice: a model for autoimmune fetal loss. Am J Obstet Gynecol. 1990;163:210–6.PubMedCrossRef

152.

Cederholm A, Svenungsson E, Jensen-Urstad K, Trollmo C, Ulfgren AK, Swedenborg J, et al. Decreased binding of annexin v to endothelial cells: a potential mechanism in atherothrombosis of patients with systemic lupus erythematosus. Arteriosclr Thromb Vasc Biol. 2005;25:198–203.

153.

Pierangeli SS, Gharavi AE, Harris EN. Experimental thrombosis and antiphospholipid antibodies: new insights. J Autoimmun. 2000;15:41–7.CrossRef

154.

Jankowski M, Vreys I, Wittevrongel C, Boon D, Vermylen J, Hoylaerts MF, et al. Thrombogenicity of beta2glycoproteinI-dependent antiphospholipid antibodies in a photochemically induced thrombosis model in the hamster. Blood. 2003;101:157–62.PubMedCrossRef

155.

Motta M, Chirico G, Rebaioli CB, Faden D, Lojacono A, Allegri F, et al. Anticardiolipin and anti-beta2 glycoprotein I antibodies in infants born to mothers with antiphospholipid antibody-positive autoimmune disease: a follow-up study. Am J Perinatol. 2006;23:247–51.PubMedCrossRef

156.

Peixoto MV, de Carvalho JF, Rodrigues CE. Clinical, laboratory, and therapeutic analyses of 21 patients with neonatal thrombosis and antiphospholipid antibodies: a literature review. J Immunol Res. 2014;2014:672603.PubMedPubMedCentralCrossRef

157.

Frauenknecht K, Katzav A, Weiss Lavi R, Sabag A, Otten S, Chapman J, et al. Mice with experimental antiphospholipid syndrome display hippocampal dysfunction and a reduction of dendritic complexity in hippocampal CA1 neurones. Neuropathol Appl Neurobiol. 2015;41:657–71.PubMedCrossRef

158.

Ross G, Sammaritano L, Nass R, Lockshin M. Effects of mothers' autoimmune disease during pregnancy on learning disabilities and hand preference in their children. Arch Pediatri Adolesc Med. 2003;157(4):397–402.CrossRef

159.

Neri F, Chimini L, Bonomi F, Filippini E, Motta M, Faden D, et al. Neuropsychological development of children born to patients with systemic lupus erythematosus. Lupus. 2004;13:805–11.PubMedCrossRef

160.

Nacinovich R, Galli J, Bomba M, Filippini E, Parrinello G, Nuzzo M, et al. Neuropsychological development of children born to patients with antiphospholipid syndrome. Arthritis Rheum. 2008;59:345–51.PubMedCrossRef

161.

Bomba M, Galli J, Nacinovich R, Ceribelli A, Motta M, Lojacono A, et al. Neuropsychiatric aid in children born to patients with rheumatic diseases. Clin Exp Rheumatol. 2010;28:767–73.PubMed

162.

Marder W, Romero VC, Ganser MA, Hyzy MA, Gordon C, McCune WJ, et al. Increased usage of special educational services by children born to mothers with systemic lupus erythematosus and antiphospholipid antibodies. Lupus Sci Med. 2014;1:e000034.PubMedPubMedCentralCrossRef

163.

Yousef Yengej FA, van Royen-Kerkhof A, Derksen R, Fritsch-Stork RDE. The development of offspring from mothers with systemic lupus erythematosus. A systematic review. Autoimmun Rev. 2017;16:701–11.PubMedCrossRef

164.

Mekinian A, Lachassinne E, Nicaise-Roland P, Carbillon L, Motta M, Vicaut E, et al. European registry of babies born to mothers with antiphospholipid syndrome. Ann Rheum Dis. 2013;72:217–22.PubMedCrossRef

165.

Nalli C, Iodice A, Andreoli L, Galli J, Lojacono A, Motta M, et al. Long-term neurodevelopmental outcome of children born to prospectively followed pregnancies of women with systemic lupus erythematosus and/or antiphospholipid syndrome. Lupus. 2017;26:552–8.PubMedCrossRef

166.

•• Groot N, de Graeff N, Avcin T, Bader-Meunier B, Dolezalova P, Feldman B, et al. European evidence-based recommendations for diagnosis and treatment of paediatric antiphospholipid syndrome: the SHARE initiative. Ann Rheum Dis. 2017;76:1637–41. The SHARE initiative was launched to develop diagnostic and management regimens for children and young adults with rheumatic diseases. This paper shows the evidence-based recommendations for diagnosis and treatment of paediatric APS. PubMedCrossRef

167.

Mehrania T, Petri M. Epidemiology of the antiphospholipid syndrome. In: Asherson RA, editor. Handbook of systemic autoimmune diseases, vol. 10. Amsterdam: Elsevier; 2009. p. 13–34.

168.

Andreoli L, Chighizola CB, Banzato A, Pons-Estel GJ, de Jesus GR, Erkan D. The estimated frequency of antiphospholipid antibodies in patients with pregnancy morbidity, stroke, myocardial infarction, and deep vein thrombosis. Arthritis Care Res (Hoboken). 2013;16:1869–73.CrossRef

Titel: Update on Antiphospholipid Syndrome: Ten Topics in 2017
verfasst von: Ilaria Cavazzana
Laura Andreoli
Maarteen Limper
Franco Franceschini
Angela Tincani
Publikationsdatum: 01.03.2018
Verlag: Springer US
Erschienen in: Current Rheumatology Reports / Ausgabe 3/2018
Print ISSN: 1523-3774
Elektronische ISSN: 1534-6307
DOI: https://doi.org/10.1007/s11926-018-0718-4

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

25.04.2024 | Hypertonie | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Update on Antiphospholipid Syndrome: Ten Topics in 2017

Abstract

Purpose of Review

Recent Findings

Summary

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Metformin rückt in den Hintergrund

Update Innere Medizin

Springer Medizin

Abstract

Purpose of Review

Recent Findings

Summary

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2018

Calcium-Containing Crystals and Osteoarthritis: an Unhealthy Alliance

What Is the Evidence for Treat-to-Target Serum Urate in Gout?

Are Doctors the Best People to Manage Gout? Is There a Role for Nurses and Pharmacists?

How Can We Improve Disease Education in People with Gout?

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Metformin rückt in den Hintergrund

Update Innere Medizin