Dtsch Med Wochenschr 2004; 129(47): 2547-2552
DOI: 10.1055/s-2004-835300
Übersichten
Hämostaseologie
© Georg Thieme Verlag Stuttgart · New York

Das Antiphospholipid-Syndrom

Klinische Manifestation, Diagnostik und TherapieThe antiphospholipid syndromeManifestation, diagnosis and therapyW. Miesbach1 , I. Scharrer1
  • 1Hämostaseologie, Zentrum der Inneren Medizin, Medizinische Klinik III, Universitätsklinik Frankfurt/Main
Further Information

Publication History

eingereicht: 2.4.2004

akzeptiert: 8.7.2004

Publication Date:
15 November 2004 (online)

Summary

Antiphospholipid antibody syndrome (APS) is characterised by the presence of frequently recurring venous and/or arterial thrombosis, abortions and repeated evidence of lupus anticoagulants and/or anticardiolipin (aCL)-antibodies. The presence of lupus anticoagulants and/or high levels of aCL-antibodies in particular increases the risk of thrombosis. At present there are several models for the systemic and cell-damaging pathogenesis of phospholipid-antibodies. Where there are repeated occurrences of thrombo-embolic complications long-term anticoagulant treatment is indicated. For patients who have APS in pregnancy, the use of low-molecular heparin and acetylsalicylic acid (ASS) is recommended. According to recent research, a large number of antibodies can be found in APS patients, which are directed against phospholipids and plasmaproteins, but partly also against individual genetic polymorphism, which suggests focussing in future on the genetic basis of APS as well as on influencing „auto-immune thrombosis” by modulating the immune system.

Literatur

  • 1 Alarcón-Segovia D, Boffa M C, Branch W. et al . Prophylaxis of the antiphospholipid syndrome: a consensus report.  Lupus. 2003;  12 499-503
  • 2 Alarcón-Segovia D, Pérez-Vázquez M E, Villa A R, Drenkard C, Cabiedes J. Preliminary classification criteria for the antiphospholipid syndrome within systemic lupus erythematosus.  Semin Arthritis Rheum. 1992;  21 275-286
  • 3 Alliot C, Messouak D, Albert F. Correction of thrombocytopenia with aspirin in the primary antiphospholipid syndrome.  Am J Hematol. 2001;  68 215
  • 4 Al-Saeed A. et al . The development of antiphospholipid antibodies in haemophilia is linked to infection with hepatitis C.  Br J Haematol. 1994;  88 845-848
  • 5 al Sayegh F A, Ensworth S, Huang S, Stein H B, Klinkhoff A V. Hemorrhagic complications of long-term anticoagulant therapy in 7 patients with systemic lupus erythematosus and antiphospholipid syndrome.  J Rheumatol. 1997;  24 1716-1718
  • 6 The APASS writing Committee . Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke.  JAMA. 2004;  291 576-584
  • 7 Asherson R A, Cervera R, de Groot P G. et al . Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines.  Lupus. 2003;  12 530-534
  • 8 Asherson R A, Cervera R, Piette J C. et al . Catastrophic antiphospholipid syndrome. Clinical and laboratory features of 50 patients.  Medicine. 1998;  77 195-207
  • 9 Asherson R A, Doherty D G, Vergani D, Khamashta M A, Hughes G R. Major histocompatibility complex assiociations with primary antiphospholipid syndrome.  Arthrits Rheum. 1992;  35 124-125
  • 10 Bentolila S, Fremeaux-Bacchi V, Weiss L, Blouin J, Kazatchkine M D, Piette J C. High frequency of C4 „null” alleles in primary antiphospholipid syndrome.  Ann Med Interne. 1996;  147 115-116
  • 11 Blank M, Faden D, Tincani A. et al . Immunization with anticardiolipin cofactor (beta-2-glycoprotein I) induces experimental antiphospholipid syndrome in naïve mice.  J Autoimmun. 1994;  7 441-455
  • 12 Brandt J T, Triplett D A, Alving B, Scharrer I. Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH.  Thromb Haemost. 1995;  74 1185-1190
  • 13 Carreno L, Monteagudo I, Lopez L F. et al . Anticardiolipin antibodies in pediatric patients with human immunodeficiency virus.  J Rheumatol. 1994;  21 1344-1346
  • 14 Cervera R, Khamashta M A, Font J. et al . Morbidity and mortality in systemic lupus erythematosus during a 5-year period. A multicenter prospective study of 1,000 patients. European Working Party on systemic lupus erythematosus.  Medicine. 1999;  78 167-175
  • 15 Cervera R, Piette J C, Font J. et al . Antiphospholipid Syndrome - Clinical and immunological manifestations and patterns of disease expression in a cohort of 1,000 patients.  Arthritis Rheum. 2002;  46 1019-1027
  • 16 Chapman J, Rand J H, Brey R L. et al . Non-stroke neurological syndromes associated with antiphospholipid antibodies: evaluation of clinical and experimental studies.  Lupus. 2003;  12 514-517
  • 17 Cheng Y, Wong R, Soo Y. et al . Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone.  N Engl J Med. 2003;  349 831-836
  • 18 Crowther M A, Ginsberg J S, Julian J. et al . A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome.  N Engl J Med. 2003;  349 1133-1138
  • 19 Diz-Kucukkaya R, Hacihanefioglu A, Yenerel M. et al . Antiphospholipid antibodies and antiphospholipid syndrome in patients presenting with immune thrombocytopenic purpura: A prospective cohort study.  Blood. 2001;  98 1760-1764
  • 20 Erkan D, Asherson R A, Espinosa G. et al . Catastrophic antiphospholipid syndrome registry project group. Long term outcome of catastrophic antiphospholipid syndrome survivors.  Ann Rheum Dis. 2003;  62 530-533
  • 21 Erkan D, Merill J T, Yazici Y, Sammaritano L, Buyon J P, Lockshin M D. High thrombosis rate after fetal loss in antiphospholipid syndrome - effective prophylaxis with aspirin.  Arthritis Rheum. 2001;  44 1466-1467
  • 22 Fabris F, Steffan A. et al . Specific antiplatelet antibodies in patients with antiphospholipid antibodies and thrombocytopenia.  Eur J Haematol. 1994;  53 232-236
  • 23 Facer C A, Agiostratidou G. High levels of anti-phospholipid antibodies in uncomplicated and severe Plasmodium falciparum and in P.vivax malaria.  Clin Exp Immunolol. 1994;  95 304-309
  • 24 Ferrara D E, Liu X, Espinola R G. et al . Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model.  Arthr Rheum. 2003;  48 3272-3279
  • 25 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
  • 26 Font J, Jiménez S, Cervera R. et al . Splenectomy for refractory Evan’s syndrome associated with antiphospholipid antibodies: report of two cases.  Ann Rheum Dis. 2000;  59 920-923
  • 27 Galli M, Barbui T. Prevalence of different anti-phospholipid antibodies in systemic lupus erythematosus and their relationship with the antiphospholipid syndrome.  Clin Chem. 2001;  47 985-987
  • 28 Galli M, Confurius P, Massau C. et al . Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor.  Lancet. 1990;  335 1544-1547
  • 29 Galli M, Daldossi M, Barbui T. Anti-glycoprotein Ib/IX and IIb/IIIa antibodies in patients with antiphospholipid antibodies.  Thromb Haemost. 1994;  71 571-575
  • 30 Galli M, Finazzi G, Bevers E M, Barbui T. Kaolin clotting time and dilute Russel’s viper venome time distinguish between prothrombin- and ß2-glycoprotein-I-dependent antiphospholipid antibodies.  Blood. 1995;  86 617-623
  • 31 Galli M, Luciani D, Bertolini G, Barbui T. Lupus anticoagulants are stronger risk factor for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature.  Blood. 2003;  101 1827-1832
  • 32 Gharavi A E, Harris E N, Asherson R A, Hughes G RV. Isotype distribution and phospholipid specifity in the antiphospholipid syndrome.  Ann Rheum Dis. 1987;  46 1-6
  • 33 Godeau B, Piette J C, Fromont P, Intrator L, Schaeffer A, Bierling P. Specific antiplatelet glycoprotein autoantibodies are associated with the thrombocytopenia or primary antiphospholipid syndrome.  Br J Haematol. 1997;  98 873-879
  • 34 Harris E N, Gharavi A E, Hedge U. et al . Anticardiolipin antibodies in autoimmune thrombocytopenic purpura.  Br J Haematology. 1985;  59 231-234
  • 35 Jung F, Miesbach W, Scharrer I. Cardiac and cerebral manifestations of antiphospholipid syndrome.  Z Kardiol. 2002;  91 650-658
  • 36 Kaburaki J, Kuwana M, Yamamoto M, Kawai S, Ikeda Y. Clinical significance of anti-annexin V antibodies in patients with systemic lupus erythematosus.  Am J Hematol. 1997;  54 209-213
  • 37 Karassa F B, Bijl M, Davies K A. et al . Role of Fc-gamma receptor IIA polymorphism in the antiphospholipid syndrome: an international meta-analysis.  Arthritis Rheum. 2003;  48 1930-1938
  • 38 Khamashta M A, Cuadrado M J, Mujic F, Taub N A, Hunt B J, Hughes G RV. The management of thrombosis in the antiphospholipid-antibody syndrome.  N Engl J Med. 1995;  332 993-997
  • 39 Kutteh W H. Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone.  Am J Obstet Gynecol. 1996;  174 1584-1589
  • 40 Lechner K, Pabinger-Fasching I. Lupus antikoagulant and thrombosis: a study of 25 cases and review of the literature.  Hemostasis. 1985;  15 254-262
  • 41 Levine S R, Brey R L, Sawaya K L. et al . Recurrent stroke and thrombo-occlusive events in the antiphospholipid syndrome.  Ann Neurol. 1995;  38 119-124
  • 42 Levine S R, Salowich-Palm L, Sawaya K L. et al . IgG anticardiolipin antibody titer > 40 GPL and the risk of subsequent thrombo-occlusive events and death. A prospective cohort study.  Stroke. 1997;  28 1660-1665
  • 43 Matsuura H, Igarasha T, Fujimoto M, Ichikawa K, Koike T. Anticardiolipin cofactor(s) and differential diagnosis of autoimmune disease.  Lancet. 1990;  336 117-118
  • 44 Mc Neil H D, Simpson R J, Chesterman C N, Krilis S A. Antiphospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta-2-glycoprotein I (apolipiprotein H).  Proc Natl Acad Sci USA. 1990;  87 4120-4124
  • 45 Merill J T. Rituximab in antiphospholipid syndrome.  Curr Rheumatol Rep. 2003;  5 381-382
  • 46 Meroni P L, Moia M, Derksen R HWM. et al . Venous thromboembolism in the antiphospholipid syndrome: management guidelines for secondary prophylaxis.  Lupus. 2003;  12 504-507
  • 47 Miesbach W, Scharrer I, Asherson R A. Recurrent life-threatening thromboembolism and catastrophic antiphospholipid syndrome in a patient despite sufficient oral anticoagulation.  Clin Rheum. 2004;  23 256-261
  • 48 Muir K W, Squire I B, Alwan W, Lees K R. Anticardiolipin antibodies in an unselected stroke population.  Lancet. 1994;  344 452-464
  • 49 Munoz-Rodríguez F J, Font J. et al . Clinical study and follow-up of 100 patients with the antiphospholipid syndrome.  Semin Arthritis Rheum. 1999;  29 182-190
  • 50 Ogasawara M, Aoki K, Matsuura E, Sasa H, Yagami Y. Anti beta 2 glycoprotein I antibodies and lupus anticoagulant in patients with recurrent pregnancy loss: prevalence and clinical significance.  Lupus. 1996;  5 587-592
  • 51 Pasquier E, Amiral J, de Saint Martin L, Mottiert D. A cross sectional study of antiphospholipid-protein antibodies in patients with venous thromboembolism.  Thromb Haemost. 2001;  86 538-542
  • 52 Pattison N S, Chamley L W, McKay E J, Liggins G C, Butler W S. Antiphospholipid antibodies in pregnancy: prevalence and clinical associations.  Br J Obstet Gynaecol. 1993;  100 909-913
  • 53 Pengo V, Biasiolo A, Brocco T, Tonett S, Ruffatti A. Autoantibodies to phospholipid -binding plasma proteins in patients with thrombosis and phospholipid-reactive antibodies.  Thromb Haemost. 1996;  75 721-724
  • 54 Petri M. Classification and epidemiology of the antiphospholipid syndrome. First edition Amsterdam: Elsevier In Asherson A, Cervera R, Piette JC, Shoenfeld Y, editors. The antiphospholipid syndrome II 2002: 11-20
  • 55 Petri M. Detection of coronary artery disease and the role of traditional risk factors in the Hopkins Lupus Cohort.  Lupus. 2000;  9 170-175
  • 56 Rand J H, Wu X X, Andree H AM. et al . Antiphospholipid antibodies accelerate plama coagulation by inhibiting annexin-V binding to phospholipids: a „Lupus procoagulant” phenomen.  Blood. 1998;  92 1652-1660
  • 57 Rosove M H, Brewer P MC. Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients.  Ann Intern Med. 1992;  117 303-308
  • 58 Salonen J T, Yla-Herttuala S, Yamamoto R. et al . Autoantibody against oxidized LDL and progression of carotid atherosclerosis.  Lancet. 1992;  339 883-887
  • 59 Schmidt R, Auer-Grumbach P, Fazekas F, Offenbacher H, Kapeller P. Anticardiolipin antibodies in normal subjects: Neuropsychological correlates and MRI findings.  Stroke. 1995;  26 749-754
  • 60 Sebastiani G D, Galeazzi M, Tincani A. et al . HLA-DPB1 alleles association of anticardiolipin and anti-beta 2GPI antibodies in a large series of European patients with systemic lupus erythematosus.  Lupus. 2003;  12 560-563
  • 61 Selva-O’Callaghan A, Ordi-Ros J, Monegal-Ferran F, Martinez N, Cortes-Hernandez F, Vilardell-Tarres M. IgA anticardiolipin antibodies - relation with other antiphospholipid antibodies and clinical significance.  Thromb Haemost. 1998;  79 282-285
  • 62 Shah N M, Khamashta M A, Atsumni T, Hughes G R. Outcome of patients with anticardiolipin antibodies: a 10 year follow-up of 52 patients.  Lupus. 1998;  7 3-6
  • 63 Shi W, Krilis S A, Chong B H, Gordon S, Chesterman C N. Prevalence of lupus anticoagulant and anticardiolipin antibodies in a healthy population.  Aust N Z J Med. 1990;  20 231-236
  • 64 Stasi R, Stipa E, Masi M. et al . Long-term observation of 208 adults with chronic idiopathic thrombocytopenic purpura.  Am J Med. 1995;  98 436-442
  • 65 Sugi T, Katsunuma J, Izumi S, McIntyre J A, Makino T. Prevalence and heterogenity of antiphosphatidylethanolamine antibodies in patients with recurrent early pregnancy losses.  Fertil Steril. 1999;  71 1060-1065
  • 66 Tincani A, Branch W, Levy R A. et al . Treatment of pregnant patients with antiphospholipid syndrome.  Lupus. 2003;  12 524-529
  • 67 Tsapanos V, Kanellopoulos N. et al . Anticardiolipin antibodies levels in healthy pregnant and non-pregnant woman.  Arch Gynecol Obstet. 2000;  263 111-115
  • 68 Wilson W A, Gharavi A E, 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
  • 69 Wisbey H L, Klestov A C. Thrombocytopenia corrected by warfarin in antiphospholipid syndrome.  J Rheum. 1996;  23 769-771
  • 70 Ziporen L, Shoenfeld Y. et al . Neurological dysfunction and hyperactive behavior associated with antiphospholipid antibodies.  J Clin Invest. 1997;  100 613-619

Dr. med. Wolfgang Miesbach

Hämostaseologie, Zentrum der Inneren Medizin, Medizinische Klinik III, Universitäts-Klinik Frankfurt/Main

Theodor-Stern-Kai 7

60590 Frankfurt

Phone: 069/63015051

Fax: 069/63016738

Email: miesbach@em.uni-frankfurt.de

    >