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Aktuelle Rheumatologie 2022; 47(06): 483-489
DOI: 10.1055/a-1927-0834
Übersichtsarbeit

Therapeutische Aspekte beim Antiphospholipidsyndrom

Therapeutic Aspects in Antiphospholipid Syndrome
Christof Specker
1   Klinik für Rheumatologie & Klinische Immunologie, Evangelische Kliniken Essen-Mitte, Essen, Germany
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Zusammenfassung

Das Antiphospholipidsyndrom (APS) wird klinisch durch venöse oder arterielle Thrombosen sowie Schwangerschaftskomplikationen gekennzeichnet und serologisch durch den Nachweis von Antiphospholipidantikörpern (aPL) bzw. eines Lupusantikoagulans (LA). In den letzten Jahren wurde evident, dass insbesondere bei Vorliegen aller drei serologischen Kriterien, Antikörper gegen Cardiolipin (aCL), gegen ß2-Glykoprotein-1 (aß2-GP1) und ein positives Lupusantikoagulans, die sog. Triple-Positivität, das Risiko für (weitere) thromboembolische und geburtshilfliche Komplikationen deutlich erhöht ist. Therapeutisch werden Thrombozytenaggregationshemmer (ASS), Heparin und Vitamin K Antagonisten eingesetzt. Von der Verwendung direkter oraler Antikoagulantien beim APS wird abgeraten. Eine Immunsuppression ist für die Vermeidung weiterer thromboembolischer Komplikationen eines APS nicht wirksam.

Abstract

The antiphospholipid syndrome (APS) is characterised clinically by venous or arterial thrombosis and pregnancy complications and serologically by the detection of antiphospholipid antibodies (aPL) or a lupus anticoagulant (LA). In recent years, it has become evident that the risk of (further) thromboembolic and obstetric complications is significantly increased if all three serological criteria are present: antibodies against cardiolipin (aCL), antibodies against ß2-glycoprotein-1 (aß2-GP1), and a positive lupus anticoagulant – a constellation called triple positivity. Low-dose aspirin (LDA), heparin and vitamin K antagonists are the mainstays of treatment. The use of direct oral anticoagulants in APS is not recommended. Immunosuppression is not effective in preventing further thromboembolic manifestations of APS.

Schlüsselwörter

Antiphospholipidsyndrom - Anticardiolipinantikörper - Lupusantikoagulans - Antikoagulation - Lupus erythematodes

Key words

antiphospholipid syndrome - anticardiolipin antibodies - anticoagulation - lupus erythematosus - lupus anticoagulant


Publikationsverlauf

Artikel online veröffentlicht:
03. November 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • Literatur

  • 1 Hughes GRV.. The antiphospholipid syndrome: ten years on Lancet 1993; 7 (342) 341-344 PubMed PMID: 8101587
    PubMedSuche in Google Scholar
  • 2 Miyakis S, Lockshin MD, Atsumi T. et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; Feb 4: 295-306
    CrossrefPubMedSuche in Google Scholar
  • 3 Moore GW.. Recent guidelines and recommendations for laboratory detection of lupus anticoagulants. Semin Thromb Hemost 2014; 40: 163-171 PubMed PMID: 24500573
    Thieme ConnectPubMedSuche in Google Scholar
  • 4 Neville C, Rauch J, Kassis J. et al. Thromboembolic risk in patients with high titre anticardiolipin and multiple antiphospholipid antibodies. Thromb Haemost 2003; Jul 90: 108-115
    Thieme ConnectPubMedSuche in Google Scholar
  • 5 Ratzinger F, Lang M, Belik S. et al. Lupus-anticoagulant testing at NOAC trough levels. Thromb Haemost 2016; Aug 1 116: 235-240
    CrossrefPubMedSuche in Google Scholar
  • 6 Lim W, Crowther MA, Eikelboom JW.. Management of Antiphospholipid Antibody Syndrome. A Systematic Review. JAMA. 2006; 295: 1050-1057
    CrossrefPubMedSuche in Google Scholar
  • 7 Roger VL, Go AS, Lloyd-Jones DM. et al. Heart disease and stroke statistics: 2011 update. A report from the American Heart Association. Circulation 2011; 123: e18-e209
    CrossrefPubMedSuche in Google Scholar
  • 8 Ruffatti A, Del Ross T, Ciprian M. et al. Antiphospholipid Syndrome Study Group of Italian Society of Rheumatology. Risk factors for a first thrombotic event in antiphospholipid antibody carriers: a prospective multicentre follow-up study. Ann Rheum Dis 2011; 70: 1083-1086
    CrossrefPubMedSuche in Google Scholar
  • 9 Pengo V, Ruffatti A, Legnani C.. Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study. Blood. 2011; Oct 27 118: 4714-4718
    CrossrefPubMedSuche in Google Scholar
  • 10 Mok CC, Tang SSK, To CH. et al. Incidence and risk factors of thromboembolism systemic lupus erythematosus: a comparison of three ethnic groups. Arthritis Rheum 2005; 52: 2774-2782
    CrossrefPubMedSuche in Google Scholar
  • 11 Levine SR, Salowich-Palm L, Sawaya KL. et al. IgG anticardiolipin antibody titer > 40 GPL and the risk of subsequent thrombo-occlusive events and death. A prospective cohort study. Stroke 1997; Sep 28: 1660-1665
    CrossrefPubMedSuche in Google Scholar
  • 12 Ruffatti A, Tonello M, Visentin MS.. Risk factors for pregnancy failure in patients with anti-phospholipid syndrome treated with conventional therapies: a multicentre, case-control study. Rheumatology (Oxford) 2011; Sep 50: 1684-1689
    CrossrefPubMedSuche in Google Scholar
  • 13 Bouvier S, Cochery-Nouvellon E, Lavigne-Lissalde G. et al. Comparative incidence of pregnancy outcomes in treated obstetric antiphospholipid syndrome: the NOH-APS observational study. Blood. 2014; 123: 404-413 PubMed PMID: 24200687
    CrossrefPubMedSuche in Google Scholar
  • 14 Yelnik CM, Laskin CA, Porter TF. 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 PubMed PMID: 268351
    CrossrefPubMedSuche in Google Scholar
  • 15 Pengo V, Biasiolo A, Pegoraro C. et al. Antibody profiles for the diagnosis of antiphospholipid syndrome. Thromb Haemost 2005; 93: 1147-1152 PubMed PMID: 15968401
    Thieme ConnectPubMedSuche in Google Scholar
  • 16 Ruffatti A, Calligaro A, Hoxha A. et al. Laboratory and clinical features of pregnant women with antiphospholipid syndrome and neonatal outcome. Arthritis Care Res 2010; 62: 302-307
    CrossrefPubMedSuche in Google Scholar
  • 17 De Carolis S, Tabacco S, Rizzo F. et al. Antiphospholipid syndrome: An update on risk factors for pregnancy outcome. Autoimmun Rev 2018; Oct 17: 956-966
    CrossrefPubMedSuche in Google Scholar
  • 18 Tektonidou MG, Andreoli L, Limper M. et al. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis 2019; Oct 78: 1296-1304
    CrossrefPubMedSuche in Google Scholar
  • 19 Buyon JP, Kim MY, Guerra MM. et al. Predictors of Pregnancy Outcomes in Patients With Lupus: A Cohort Study. Ann Intern Med 2015; Aug 4 163: 153-163
    CrossrefPubMedSuche in Google Scholar
  • 20 Espinosa G, Cervera R.. Current treatment of antiphospholipid syndrome: lights and shadows. Nat Rev Rheumatol 2015; Oct 11: 586-596
    CrossrefPubMedSuche in Google Scholar
  • 21 Rubenstein E, Arkfeld DG, Metyas S. et al. Rituximab treatment for resistant antiphospholipid syndrome. J Rheumatol 2006; 33: 355
    PubMedSuche in Google Scholar
  • 22 Shapira I, Andrade D, Allen SL. et al. Brief report: induction of sustained remission in recurrent catastrophic antiphospholipid syndrome via inhibition of terminal complement with eculizumab. Arthritis Rheum 2012; 64: 2719
    CrossrefPubMedSuche in Google Scholar
  • 23 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
    CrossrefPubMedSuche in Google Scholar
  • 24 Cervera R, Rodríguez-Pintó I, Espinosa G. on behalf of the Task Force on Catastrophic Antiphospholipid Syndrome. Catastrophic antiphospholipid syndrome: task force report summary. Lupus. 2014; 23: 1283-1285 PMID: 25228727
    CrossrefPubMedSuche in Google Scholar
  • 25 Specker C, Dörner T, Schneider M.. Hot Topic: Direkte orale Antikoagulanzien (DOACs) beim Antiphospholipidsyndrom?. Z Rheumatol 2019; Aug 78: 493-494
    CrossrefPubMedSuche in Google Scholar
  • 26 Cuadrado MJ, Bertolaccini ML, Seed PT. et al. Low-dose aspirin vs low-dose aspirin plus low-intensity warfarin in thromboprophylaxis: a prospective, multicentre, randomized, open, controlled trial in patients positive for antiphospholipid antibodies (ALIWAPAS). Rheumatology 2014; 53: 275-284
    CrossrefPubMedSuche in Google Scholar
  • 27 Arnaud L, Mathian A, Ruffatti A. et al. Efficacy of aspirin for the primary prevention of thrombosis in patients with antiphospholipid antibodies: An international and collaborative meta-analysis. Autoimmunity Reviews 2014; 13: 281-291
    CrossrefPubMedSuche in Google Scholar
  • 28 Tektonidou MG, Laskari K, Panagiotakos DB. et al. Risk factors for thrombosis and primary thrombosis prevention in patients with systemic lupus erythematosus with or without antiphospholipid antibodies. Arthritis Rheum 2009; Jan 15 61: 29-36
    CrossrefPubMedSuche in Google Scholar
  • 29 Ruiz-Irastorza G, Crowther M, Branch W. et al. Antiphospholipid syndrome. Lancet 2010; 376: 1498-1509 PMID: 20822807
    CrossrefPubMedSuche in Google Scholar
  • 30 Ruiz-Irastorza G, Cuadrado MJ, Ruiz-Arruza I. 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: 206-218
    CrossrefPubMedSuche in Google Scholar
  • 31 Fonseca MES, Balbi GGM, Signorelli F. et al. CoaguChek® XS versus standard laboratory prothrombin time for anticoagulant monitoring in patients with antiphospholipid syndrome. Lupus. 2022. 31. 565-574 Erratum in: Lupus. 2022 Mar 30; 9612033221093474. PMID: 35266798.
    CrossrefSuche in Google Scholar
  • 32 Masucci M, Li Kam Wa A, Shingleton E. et al. Point of care testing to monitor INR control in patients with antiphospholipid syndrome. eJHaem 2022; July 9 1-4
    CrossrefPubMedSuche in Google Scholar
  • 33 Dufrost V, Risse J, Reshetnyak T. et al. Increased risk of thrombosis in antiphospholipid syndrome patients treated with direct oral anticoagulants. Results from an international patient-level data meta-analysis. Autoimmun Rev 2018; Oct 17: 1011-1021
    CrossrefPubMedSuche in Google Scholar
  • 34 Pengo V, Denas G, Zoppellaro G. et al. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood. 2018; Sep 27 132: 1365-1371
    CrossrefPubMedSuche in Google Scholar
  • 35 Dufrost V, Wahl D, Zuily S.. Direct oral anticoagulants in antiphospholipid syndrome: Meta-analysis of randomized controlled trials. Autoimmun Rev 2021; Jan 20: 102711
    CrossrefPubMedSuche in Google Scholar
  • 36 Koval N, Alves M, Plácido R. et al. Direct oral anticoagulants versus vitamin K antagonists in patients with antiphospholipid syndrome: systematic review and meta-analysis. RMD Open 2021; Jul 7: e001678
    CrossrefPubMedSuche in Google Scholar
  • 37 Woller SC, Stevens SM, Kaplan D. et al. Apixaban compared with warfarin to prevent thrombosis in thrombotic antiphospholipid syndrome: a randomized trial. Blood Adv 2022; Mar 22 6: 1661-1670
    CrossrefPubMedSuche in Google Scholar
  • 38 Woller SC, Stevens SM, Kaplan DA. et al. Protocol modification of apixaban for the secondary prevention of thrombosis among patients with antiphospholipid syndrome study. Clin Appl Thromb Hemost 2018; 24: 192
    CrossrefPubMedSuche in Google Scholar
  • 39 European Medicines Agency (EMA). PRAC recommendations on signals 2019 https://www.ema.europa.eu/en/documents/pracrecommendation/prac-recommendations-signals-adopted-8-11-april-2019-prac-meeting_en.pdf
    PubMed
  • 40 Konstantinides SV, Meyer G, Becattini C. et al. ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J 2020; Jan 21 41: 543-603
    Suche in Google Scholar
  • 41 https://www.bfarm.de/SharedDocs/Risikoinformationen/Pharmakovigilanz/DE/RHB/2019/rhb-doaks.html
    PubMed
  • 42 Fischer-Betz R, Specker C.. Rheumatische Erkrankungen und Schwangerschaft – Ein Ratgeber für die Praxis. Düsseldorf University Press. 2016 ISBN-10: 3957580358
    PubMedSuche in Google Scholar
  • 43 Fischer-Betz R, Specker C.. Pregnancy in systemic lupus erythematosus and antiphospholipid syndrome. Best Pract Res Clin Rheumatol 2017; Jun 31: 397-414
    CrossrefPubMedSuche in Google Scholar
  • 44 Sciascia S, Branch DW, Levy RA. et al. The efficacy of hydroxychloroquine in altering pregnancy outcome in women with antiphospholipid antibodies. Evidence and clinical judgment. Thromb Haemost 2016; Jan 27 115: 285-290
    CrossrefPubMedSuche in Google Scholar
  • 45 Andreoli L, Bertsias GK, Agmon-Levin 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: 476-485 PMID: 27457513
    CrossrefPubMedSuche in Google Scholar