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Aktuelle Rheumatologie 2003; 28(3): 131-137
DOI: 10.1055/s-2003-40444
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Antiphospholipid-Antikörper und Schwangerschaft

Antiphospholipid Antibodies and PregnancyR. Fischer-Betz1 , C. Specker2
  • 1Klinik für Nephrologie & Rheumatologie, Heinrich-Heine-Universität Düsseldorf
  • 2Klinik für Rheumatologie & Klinische Immunologie, Katholisches Krankenhaus St. Josef, Kliniken Essen-Süd
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Publication History

Publication Date:
07 July 2003 (online)

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Zusammenfassung

Patientinnen mit Antiphospholipidsyndrom (APS) haben eine gesteigerte Rate an Schwangerschaftskomplikationen. Neben Wachstumsretardierung der Frucht, Frühgeburten und einer gesteigerten Gestoseneigung kommt es insbesondere im 2. und 3. Trimenon häufig zu Aborten. Wie auch bei anderen klinischen Manifestationen des APS sind hierfür Gefäßverschlüsse verantwortlich, die zu plazentaren Infarkten und damit zur Minderperfusion der Frucht führen. Da eine Antikoagulation mit Thrombocytenaggregationshemmern und Heparin in der Lage zu sein scheint, die plazentare Durchblutung zu verbessern, ist das Erkennen gefährdeter Patientinnen, deren Beratung, Behandlung und engmaschige Überwachung in der Schwangerschaft Voraussetzung, um mehr dieser Hochrisikoschwangerschaften erfolgreich zu Ende zu führen. Zur Vermeidung postpartaler Komplikationen beim APS (Thrombosen im Wochenbett, HELLP-Syndrom) ist auch nach der Entbindung eine Antikoagulation und genaue Überwachung zu empfehlen. Abraten wird man von einer Schwangerschaft daher bei APS-Patientinnen inzwischen nur bei aktiver Grunderkrankung (SLE), insbesondere bei Nierenbeteiligung, schlecht einstellbarer Hypertonie und bei schweren zentralnervösen Komplikationen in der Vorgeschichte.

Abstracts

Female patients with antiphospholipid syndrome (APS) suffer from an increased rate of pregnancy complications. Not only is the growth of the fetus retarded; there is also a tendency to premature birth and an increased tendency to gestosis. In particular, abortions are frequent in the second or third trimenon. Vascular occlusions are responsible for these and other clinical manifestations of APS, resulting in placental infarctions and hence deficient perfusion of the fetus. For a successful management of a greater proportion of these high-risk pregnancies it is essential to recognise such risks at an early date and to advise and treat the patients, for it appears that anticoagulation with thrombocyte aggregation inhibitors and heparin can improve the placental blood flow. Even after birth we recommend anticoagulation and close follow-up to avoid postpartal complications in APS (thromboses during childbed, HELLP syndrome). Hence, we would now discourage pregnancy in APS patients only in case of an active underlying disease (SLE), especially with kidney involvement, maladjustable hypertonia and severe central nervous complications in the patient’s previous history.

  • 1 Conley C L, Hartmann R C. A hemorrhagic disorder caused by circulating anticoagulant in patients with disseminated LE.  J Clin Invest. 1952;  31 621-62
    PubMedGoogle Scholar
  • 2 Margolius A J, Jackson D P, Ratnoff O D. Circulating anticoagulants: a study of 40 cases and a review of the literature.  Medicine. 1961;  40 145-202
    PubMedGoogle Scholar
  • 3 Bowie E JW, Thompson J H, Pascuzzi C A. et al . Thrombosis in SLE despite circulating anticoagulants.  J Lab Clin Med. 1963;  9 416-430
    PubMedGoogle Scholar
  • 4 Feinstein D J, Rapaport S J. Acquired inhibitors of blood coagulation. Spaet TN Prog Haemostas Thromb (1st Edition) New York; Grune and Stratton 1972: 75-95
    Google Scholar
  • 5 Lechner K. Acquired inhibitors in non-hemophilic patients.  Haemostasis. 1974;  3 65-93
    PubMedGoogle Scholar
  • 6 Thiagarajan P, Shapiro S S, DeMarco L. Monoclonal immunoglobulin M coagulation inhibitor with phospholipid specifity.  J Clin Invest. 1980;  66 397-405
    CrossrefPubMedGoogle Scholar
  • 7 Harris E N, Gharavi A E, Boey M L. et al . Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in SLE.  Lancet. 1983;  II 1211-1214
    PubMedGoogle Scholar
  • 8 Harris E N, Gharavi A E, Hughes G RV. Anti-phospholipid antibodies.  Clin Rheum Dis. 1985;  11 591-609
    PubMedGoogle Scholar
  • 9 Harris E N, Asherson R A, Gharavi A E. et al . Thrombocytopenia in SLE and related autoimmune disorders: association with anticardiolipin antibody.  Br J Haematol. 1985;  59 227-230
    PubMedGoogle Scholar
  • 10 Hughes G RV. The anticardiolipin syndrome.  Clin Exp Rheumatol. 1985;  3 285-286
    PubMedGoogle Scholar
  • 11 Harris E N. Syndrome of the black swan.  Br J Rheumatol. 1987;  26 324-332
    CrossrefPubMedGoogle Scholar
  • 12 http: //www.nlm.nih.gov/cgi/mesh/2003/MB_cgi#TreeC20.111.197. 
    Google Scholar
  • 13 Alarcon-Segovia D, Deleze M, Oria C V. et al . Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus. A prospective analysis of 500 consecutive patients.  Medicine. 1989;  68 353-356
    PubMedGoogle Scholar
  • 14 The antiphospholipid antibodies in stroke study group . Clinical and laboratory findings in patients with antiphospholipid antibodies and cerebral ischemia.  Stroke. 1990;  21 1268-1273
    PubMedGoogle Scholar
  • 15 Brey R L, Hart R G, Sherman D G. et al . Antiphospholipid antibodies and cerebral ischemia in young people.  Neurology. 1990;  40 1190-1196
    PubMedGoogle Scholar
  • 16 Hughes G RV. The antiphospholipid syndrome: ten years on.  Lancet. 1993;  342 341-344
    CrossrefPubMedGoogle Scholar
  • 17 Wilcox A J, Weinberg C R, o’Connor J F. et al . Incidence of early loss of pregnancy.  N Engl J Med. 1988;  319 189-194
    CrossrefPubMedGoogle Scholar
  • 18 Miller J F, Williamson E, Glue J. et al . Fetal loss after implantation: a prospective study.  Lancet. 1980;  ii 554-556
    PubMedGoogle Scholar
  • 19 Edmonds D K, Lindsay K S, Miller J F. et al . Early embryonic mortality in woman.  Fertil Steril. 1982;  38 447-453
    PubMedGoogle Scholar
  • 20 Samueloff A, Xenakis E M, Berkus M D. et al . Recurrent stillbirth. Significance and characteristics.  J Reprod Med. 1993;  38 (11) 883-886
    PubMedGoogle Scholar
  • 21 Oyen N, Skjaerven R, Irgens L M. Population-based recurrence risk of sudden infant death syndrome compared with other infant and fetal deaths.  Am J Epidemiol. 1996;  144 300-305
    PubMedGoogle Scholar
  • 22 Stern J J, Dorfmann A D, Gutierrez-Najar A J. et al . Frequency of abnormal karyotypes among abortuses from women with and without a history of recurrent spontaneous abortion.  Fertil Steril. 1996;  65 (2) 250-253
    PubMedGoogle Scholar
  • 23 Nilsson I M, Astedt B, Hedner U. et al . Intrauterine death and the circulating anticoagulant.  Acta M S. 1975;  197 153-159
    PubMedGoogle Scholar
  • 24 Lubbe W F, Butler W S, Palmer S J. et al . Lupus anticoagulant in pregnancy.  B J Obst Gyn. 1984;  91 357-363
    PubMedGoogle Scholar
  • 25 Ramsey-Goldman R, Kutzer J E, Kuller L H. et al . Pregnancy outcome and anti-cardiolipin antibody in women with systemic lupus erythematosus.  Am J Epidemiol. 1993;  138 1057-1069
    PubMedGoogle Scholar
  • 26 Branch D W. Thoughts on the mechanism of pregnancy loss associated with the antiphospholipid syndrome.  Lupus. 1994;  3 275-280
    PubMedGoogle Scholar
  • 27 Love P E, Santoro S A. Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in SLE and in non-SLE disorders.  Ann Intern Med. 1990;  112 682-698
    CrossrefPubMedGoogle Scholar
  • 28 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
    CrossrefPubMedGoogle Scholar
  • 29 Branch D W, Silver R M. Criteria for antiphospholipid syndrome: early fetal loss, or recurrent pregnancy loss.  Lupus. 1996;  5 409-413
    PubMedGoogle Scholar
  • 30 Loizou S, Byron M A, Englert H J. et al . Association of quantitative anticardiolipin antibody levels with fetal loss and time of loss in SLE.  Q J Med. 1988;  255 525-531
    PubMedGoogle Scholar
  • 31 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
  • 32 Infante-Rivard C, David M, Gauthier R. et al . Lupus anticoagulants, anticardiolipin antibodies, and fetal loss - A case-control study.  N Engl J Med. 1991;  325 1063-1066
    PubMedGoogle Scholar
  • 33 Howard M A, Firkin B G, Healy D L. et al . Lupus anticoagulant in women with multiple spontaneous miscarriage.  Am J Haematol. 1987;  26 175-178
    PubMedGoogle Scholar
  • 34 Oshiro B T. et al . Antiphospholipid antibodies and fetal deaths.  Obstet Gynecol. 1996;  87 489-493
    CrossrefPubMedGoogle Scholar
  • 35 Specker C. Assoziation der aCL zu klinischen Komplikationen. Das Antiphospholipidsyndrom - Bedeutung der Antiphospholipid-Antikörper für Diagnose, Differenzialdiagnose, Prognose und Therapie des systemischen Lupus Erythematodes (Habilitationsschrift, Kap. 3.1.4) Aachen; Shaker Verlag 2002: 34-37
    Google Scholar
  • 36 Specker C, Rademacher J, Söhngen D. et al . Cerebral microemboli in patients with antiphospholipid syndrome.  Lupus. 1997;  6 638-644
    PubMedGoogle Scholar
  • 37 Silver R M, Porter T F, van Leeuwen I. et al . Anticardiolipin antibodies: clinical consequences of “low titers”.  Obstet Gynecol. 1996;  89 549-655
    PubMedGoogle Scholar
  • 38 Porter T F, Silver R M, Branch D W. Pregnancy loss and antiphospholipid antibodies. Khamashta MA Hughes Syndrome - Antiphospholipid Syndrome London; Springer 2000: 179-194
    Google Scholar
  • 39 Specker C. Assoziation der aPL zu klinischen Komplikationen. Das Antiphospholipidsyndrom - Bedeutung der Antiphospholipid-Antikörper für Diagnose, Differenzialdiagnose, Prognose und Therapie des systemischen Lupus Erythematodes (Habilitationsschrift, Kap. 4.5) Aachen; Shaker Verlag 2002: 64-72
    Google Scholar
  • 40 Sammaritano L R, Gharavi A E. Antiphospholipid antibodies and placental anticoagulant protein I.  Lupus. 1994;  3 263-265
    PubMedGoogle Scholar
  • 41 Branch D W, Dudley D J, Mitchell M D. 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;  163 210-216
    CrossrefPubMedGoogle Scholar
  • 42 Rand J H, Xiao-Xuan W, Andree H AM. et al . Pregnancy loss in the antiphospholipid syndrome - a possible thombogenic mechanism.  N Engl J Med. 1997;  337 154-160
    CrossrefPubMedGoogle Scholar
  • 43 Lubbe W F, Butler W S, Palmer S J. et al . Fetal survival after prednisone suppression of maternal lupus-anticoagulant.  Lancet. 1983;  18 (1) 1361-1363
    PubMedGoogle Scholar
  • 44 Cowchock S, Reece E A. Do low-risk pregnant women with antiphospholipid antibodies need to be treated? Organizing Group of the Antiphospholipid Antibody Treatment Trial.  Am J Obstet Gynecol. 1997;  176 1099-1100
    CrossrefPubMedGoogle Scholar
  • 45 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
    CrossrefPubMedGoogle Scholar
  • 46 Rai R S, Regan L, Dave M. et al . Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with antiphospholipid antibodies.  BMJ. 1997;  314 253-257
    CrossrefPubMedGoogle Scholar
  • 47 Balasch J, Carmona F, Lopez-Soto A. et al . Low-dose aspirin for prevention of pregnancy losses in women with primary antiphospholipid syndrome.  Hum Reprod. 1993;  8 2234-2239
    PubMedGoogle Scholar
  • 48 Farquharson R G, Quenby S, Greaves M. Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment.  Obstet Gynecol. 2002;  100 408-413
    CrossrefPubMedGoogle Scholar
  • 49 Branch D W, Peaceman A M, Druzin M. et al . A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. The Pregnancy Loss Study Group.  Am J Obstet Gynecol. 2000;  182 122-127
    CrossrefPubMedGoogle Scholar
  • 50 Triolo G, Ferrante A, Ciccia F. et al . Randomized study of subcutaneous low molecular weight heparin plus aspirin versus intravenous immunoglobulin in the treatment of recurrent fetal loss associated with antiphospholipid antibodies.  Arthritis Rheum. 2003;  48 728-731
    CrossrefPubMedGoogle Scholar
  • 51 Ginsberg J S, Hirsh J. Use of antithrombotic agents during pregnancy.  Chest. 1998;  114 (5 Suppl) 524-530
    PubMedGoogle Scholar
  • 52 Balasch J, Cervera R. Reflections on the management of reproductive failure in the antiphospholipid syndrome - the clinician’s perspective.  Lupus. 2002;  11 467-477
    CrossrefPubMedGoogle Scholar
  • 53 Bazzan M, Donvito V. Low-molecular-weight heparin during pregnancy.  Thromb Res. 2001;  101 175-186
    CrossrefPubMedGoogle Scholar
  • 54 Warkentin T E, Levine M N, Hirsh J. et al . Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin.  N Engl J Med. 1995;  332 1330-1335
    CrossrefPubMedGoogle Scholar

Priv.-Doz. Dr. C. Specker

Klinik für Rheumatologie & Klinische Immunologie, Katholisches Krankenhaus St. Josef. Zentrum für Innere Medizin der Kliniken Essen Süd

Propsteistraße 2

45239 Essen

Email: specker@rheumanet.org