PDF herunterladen
Arthritis und Rheuma 2011; 31(04): 247-256
DOI: 10.1055/s-0037-1618073
Systemischer Lupus erythematodes
Schattauer GmbH

Antiphospholipid-Syndrom

Update zu Diagnose und TherapieThe antiphospholipid syndrome (APS) – diagnosis and treatmentUpdate on diagnosis and therapy
Ch. Specker
1   Klinik für Rheumatologie und Klinische Immunologie, Zentrum für Innere Medizin der Kliniken Essen Süd, Rheumazentrum Rhein-Ruhr, Essen
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
26. Dezember 2017 (online)

    Lizenzen und Reprints

Zusammenfassung

Das Antiphospholipid-Syndrom (APS) ist gekennzeichnet durch eine gesteigerte Thromboseneigung bei serologischem Nachweis erhöhter Antiphospholipid-Antikörper (Anticardiolipin-Antikörper, Antikörper gegen β2Glykoprotein I) oder eines sogenannten Lupus-Antikoagulans. Es findet sich in ca. 20 bis 30 Prozent der Fälle mit systemischem Lupus erythematodes (sekundäres APS), kann aber auch isoliert auftreten (primäres APS). Ursache für die vielfältigen klinischen Manifestationen des APS sind thrombembolische Gefäßverschlüsse venöser oder arterieller Blutgefäße unterschiedlicher Größe und in verschiedenen Organsystemen. Häufigste Manifestationen sind tiefe Beinvenenthrombosen, Lungenembolien und zerebrovaskuläre Ischämien. Durch Obliteration plazentarer Gefäße kommt es auch zu einer gesteigerten Abortneigung, vorzugsweise jenseits der zehnten Schwangerschaftswoche. Ein APS korrekt zu diagnostizieren ist nicht einfach. Nicht jede Thrombose bei Nachweis von Antiphospholipid-Antikörpern ist Ausdruck eines Antiphospholipid-Syndroms und die Abschätzung des Thromboserisikos sowie Art und Intensität einer geeigneten Thromboseprophylaxe sind nach wie vor eine Herausforderung in der Betreuung von APS-Patienten. Eine Immunsuppression ist in der Behandlung des APS nicht wirksam. In dieser Arbeit werden die mehrfach überarbeiteten Klassifikationskriterien des APS, die Labordiagnostik und die aktuellen Empfehlungen zur Therapie dargestellt.

Summary

The antiphospholipid syndrome (APS) is characterized by recurrent arterial or venous thromboembolism or pregnancy loss, in association with antibodies directed against anionic phospholipids or against plasma proteins bound to anionic phospholipids. It occurs in 20 to 30 % of patients suffering from systemic lupus erythematosus (secondary APS) but is also found without underlying connective tissue disease (primary APS). Cause of the huge variety in clinical manifestations is vaso-occlusive disease and not vasculitis in venous or arterial blood vessels of different size and sites (i. e. deep vein thrombosis, pulmonary embolism, cerebro-vascular disease). In accordance to this also fetal abortion, typically beyond the 10th week of gestation, is caused by infarctions of blood vessels in the placenta. Establishing the correct diagnosis of APS is not easy. Thrombosis might occur due to other reasons even in patients with antiphospholipid antibodies and to estimate the risk of thrombotic complications is challenging, as well as the question if, which, how long and in what strength anticoagulation is recommended. The several times revised classification criteria of APS, issues on laboratory diagnosis and current therapeutic recommendations are discussed in this paper.

Schlüsselwörter

Antiphospholipid-Syndrom - Thrombophilie - Anticardiolipin-Antikörper - Lupus-Antikoagulans - Antikoagulation - systemischer Lupus erythematodes

Keywords

Antiphospholipid syndrome - thromboembolism - anticardiolipin antibodies - lupus anticoagulant - anticoagulation - systemic lupus
 

  • Literatur

  • 1 Feinstein DJ, Rapaport SJ. Acquired inhibitors of blood coagulation. In: Spaet TN. ed. Prog Haemostas Thromb. 1st edition. New York: Grune and Stratton; 1972: 75-95.
    Google Scholar
  • 2 Harris EN, Chan JKH, Asherson RA. et al. Thrombosis, recurrent fetal loss and Thrombocytopenia. Arch Intern Med 1986; 146: 2153-2156.
    CrossrefPubMedGoogle Scholar
  • 3 Harris EN, Hughes GRV, Gharavi AE. The antiphospholipid antibody syndrome. J Rheumatol 1987; 13 (Suppl) 210.
    Google Scholar
  • 4 Hughes GRV. The antiphospholipid syndrome: ten years on. Lancet 1993; 342: 341-344.
    CrossrefPubMedGoogle Scholar
  • 5 Wilson WA, Gharavi AE, Koike T. et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 1999; 42: 1309-1311.
    CrossrefPubMedGoogle Scholar
  • 6 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; 4 (02) 295-306.
    CrossrefPubMedGoogle Scholar
  • 7 Mujic F, Cuadrado MJ, Lloyd M. et al. Primary antiphospholipid syndrome evolving into systemic lupus erythematosus. J Rheumatol 1995; 22 (08) 1589-1592.
    Google Scholar
  • 8 Specker Ch. Das Antiphospholipidsyndrom. Aachen: Shaker Verlag; 2002
    Google Scholar
  • 9 Vianna JL, Khamashta MA, Ordi-Ros J. et al. Comparison of the primary and secondary Antiphospholipid Syndrome: A european multicenter study of 114 patients. Am J Med 1994; 96: 3-9.
    CrossrefPubMedGoogle Scholar
  • 10 Wisloff F, Jacobsen EM, Liestol S. Laboratory diagnosis of the antiphospholipid syndrome. Thromb Res 2002; 108 (5–6) 263-271.
    CrossrefPubMedGoogle Scholar
  • 11 Harris EN, Pierangeli SS. Functional effects of anticardiolipin antibodies. Lupus 1996; 5: 372-377.
    CrossrefPubMedGoogle Scholar
  • 12 Lim W, Crowther MA, Eikelboom JW. Management of Antiphospholipid Antibody Syndrome. A Systematic Review. JAMA 2006; 295: 1050-1057.
    CrossrefPubMedGoogle Scholar
  • 13 Bertolaccini ML, Roch B, Amengual O. et al. Multiple antiphospholipid tests do not increase the diagnostic yield in antiphospholipid syndrome. Br J Rheumatol 1998; 37: 1229-1232.
    CrossrefPubMedGoogle Scholar
  • 14 Sheng Y, Kandiah DA, Krilis SA. Beta2-glycoprotein I: target antigen for 'antiphospholipid' antibodies. Immunological and molecular aspects. Lupus 1998; 7 (Suppl. 02) S5-S9.
    CrossrefPubMedGoogle Scholar
  • 15 McNally et al. The use of anti-β2-glycoprotein I assay for discrimination between anticardiolipin antibodies associated with infection and increased risk for thrombosis. Br J Haematology 1995; 91: 471-473.
    CrossrefPubMedGoogle Scholar
  • 16 Neville C, Rauch J, Kassis J. et al. Thromboembolic risk in patients with high titre anticardiolipin and multiple antiphospholipid antibodies. Thromb Haemost 2003; 90 (01) 108-115.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 17 Meroni PL, Rivolta R, Ghidoni P. Histopathological findings in cases of systemic lupus erythematosus-associated antiphospholipid syndrome. Clin Rheumatol 1991; 10: 211-214.
    CrossrefPubMedGoogle Scholar
  • 18 Hughson MD, McCarty GA, Brumback RA. Spectrum of vascular pathology affecting patients with the antiphospholipid syndrome. Hum Patol 1995; 26: 716-724.
    Google Scholar
  • 19 Erkan D, Yazici Y, Peterson MG. et al. A cross-sectional study of clinical thrombotic risk factors and preventive treatments in antiphospholipid syndrome. Rheumatology (Oxford) 2002; 41 (08) 924-929.
    CrossrefPubMedGoogle Scholar
  • 20 Giron-Gonzalez JA, Garcia del Rio E, Rodriguez C. et al. Antiphospholipid syndrome and asymptomatic carriers of antiphospholipid antibody: prospective analysis of 404 individuals. J Rheumatol 2004; 31 (08) 1560-1567.
    Google Scholar
  • 21 Brey RL, Escalante A. Neurological manifestations of antiphospholipid antibody syndrome. Lupus 1998; 7 (Suppl. 02) S67-S74.
    CrossrefPubMedGoogle Scholar
  • 22 Cervera R, Piette JC, Font J. et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum 2002; 46 (04) 1019-1027.
    CrossrefPubMedGoogle Scholar
  • 23 Sinico RA, Cavazzana I, Nuzzo M. et al. Renal involvement in primary antiphospholipid syndrome: retrospective analysis of 160 patients. Clin J Am Soc Nephrol 2010; 5 (07) 1211-1217 PubMed PMID: 20430943; PubMed Central PMCID: PMC2893064.
    CrossrefPubMedGoogle Scholar
  • 24 Fischer-Betz R, Specker C. Antiphospholipid-Antikörper und Schwangerschaft. Akt Rheumatol 2003; 28: 131-137.
    Artikel in Thieme ConnectGoogle Scholar
  • 25 Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet 1999; 353: 1167-1173.
    CrossrefPubMedGoogle Scholar
  • 26 Asherson RA. The catastrophic antiphospholipid antibody syndrome. J Rheumatol 1992; 19: 508-512.
    Google Scholar
  • 27 Cervera R, Bucciarelli S, Plasín MA. et al; Catastrophic Antiphospholipid Syndrome (CAPS) Registry Project Group (European Forum On Antiphospholipid Antibodies). Catastrophic antiphospholipid syndrome (CAPS): descriptive analysis of a series of 280 patients from the „CAPS Registry“. J Autoimmun 2009; 32 (3–4) 240-245.
    CrossrefPubMedGoogle Scholar
  • 28 Cervera R. et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum 2002; 46 (04) 1019-1027.
    CrossrefPubMedGoogle Scholar
  • 29 Asherson RA, Cervera R, de Groot PG. et al Catastrophic Antiphospholipid Syndrome Registry Project Group. Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus 2003; 12 (07) 530-534.
    CrossrefPubMedGoogle Scholar
  • 30 Asherson RA, Espinosa G, Cervera R. et al. Disseminated intravascular coagulation in catastrophic antiphospholipid syndrome: clinical and haematological characteristics of 23 patients. Ann Rheum Dis 2005; 64 (06) 943-946.
    CrossrefPubMedGoogle Scholar
  • 31 Levine SR, Salowich-Palm L, Sawaya KL. et al. IgG anti-cardiolipin antibody titer > 40 GPL and the risk of subsequent thrombo-occlusive events and death. A prospective cohort study. Stroke 1997; 28 (09) 1660-1665.
    CrossrefPubMedGoogle Scholar
  • 32 Finazzi G, Brancaccio V, Moia M. et al. Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a four-year prospective study from the italian registry. Am J Med 1996; 100: 530-536.
    CrossrefPubMedGoogle Scholar
  • 33 Ruffatti A, Del Ross T, Ciprian M. et al. Risk factors for a first thrombotic event in antiphospholipid antibody carriers. A multicentre, retrospective follow-up study. Ann Rheum Dis 2009; 68 (03) 397-399 PubMed PMID: 18812393.
    CrossrefPubMedGoogle Scholar
  • 34 Ginsburg KS, Liang MH, Newcomer L. et al. Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. Ann Inn Med 1992; 117: 997-1002.
    Google Scholar
  • 35 Infante-Rivard C, David M, Gauthier R, Rivard GE. Lupus anticoagulants, anticardiolipin antibodies, and fetal loss – A case-control study. N Engl J Med 1991; 325: 1063-1066.
    CrossrefPubMedGoogle Scholar
  • 36 Janardhan V, Wolf PA, Kase CS. et al. Anticardiolipin antibodies and risk of ischemic stroke and transient ischemic attack: the Framingham cohort and offspring study. Stroke 2004; 35: 736-741.
    CrossrefPubMedGoogle Scholar
  • 37 Bucciarelli S, Espinosa G, Cervera R. 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 (08) 2568-2576.
    CrossrefPubMedGoogle Scholar
  • 38 Bermas BL, Schur PH, Kaplan AA. Prognosis and therapy of the antiphospholipid antibody syndrome. In: UpToDate Basow DS. (Ed), UpToDate Waltham, MA: 2011. (19.1) www.uptodate.com/home/help/faq/using_UTD/index.html#cite
    Google Scholar
  • 39 Erkan D, Harrison MJ, Levy R. 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 (07) 2382-2391.
    CrossrefPubMedGoogle Scholar
  • 40 Ruiz-Irastorza G, Crowther M, Branch W, Khamashta MA. Antiphospholipid syndrome. Lancet 2010; 376: 1498-1509.
    CrossrefPubMedGoogle Scholar
  • 41 Schulman S, Svenungsson E, Granqvist S. Duration of Anticoagulation Study Group. Anticardiolipin antibodies predict early recurrence of thromboembolism and death among patients with venous thromboembolism following anticoagulant therapy. Am J Med 1998; 104: 332-338.
    CrossrefPubMedGoogle Scholar
  • 42 Levine SR, Brey RL, Tilley BC. et al. APASS Investigators. Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke. JAMA 2004; 291 (05) 576-584.
    CrossrefPubMedGoogle Scholar