Antiphospholipid-Antikörper und andere hämostaseologische Veränderungen bei Patientinnen mit früher schwerer Präeklampsie oder HELLP-Syndrom in der Anamnese

Zusammenfassung

Fragestellung: Wir untersuchten 61 Frauen mit schwerer Präeklampsie oder HELLP-Syndrom vor der 34. SSW mindestens 6 Monate postpartum auf angeborene oder erworbene Gerinnungsdefekte.Patienten und Methoden: Wir verglichen diese Gruppe mit 61 Frauen ohne Schwangerschaftskomplikationen.Ergebnisse: Wir fanden in 20 % eine Faktor V Leiden Mutation gegenüber 5 % in der Normalgruppe (OR 4,7, 95 % CI 1,4 - 15,8, p = 0,003). In 41 % konnten wir wiederholt Antikardiolipin-Antikörper nachweisen und in 3 % in der Kontrollgruppe (OR 20,5, 95 % CI 5,2 - 81,4, p = 0,001). In 54 % konnte eine Lupusantikoagulanz nachgewiesen werden gegenüber 3 % in der Kontrollgruppe (OR 34,8, 95 % CI 8,9 - 134,7, p < 0,001). Ein Protein C/S-Mangel trat in 10 % der Patientinnen mit Präeklampsie/HELLP auf, dagegen nur in 5 % in der Gruppe mit unkomplizierter Schwangerschaft (OR 2,1, 95 % CI 0,6 - 8,0, p = 0,25). In 16,4 % war eine chronische Hypertonie und in 20 % ein wiederholter Abort anamnestisch und klinisch nachzuweisen. In der Kontrollgruppe traten diese Ereignisse nicht auf.Schlußfolgerung: Bei Frauen mit schwerer Präeklampsie oder HELLP-Syndrom findet sich eine hohe Inzidenz für angeborene oder erworbene Gerinnungsdefekte.

Abstract

Objective: To evaluate the presence of thrombophilic defects in patients with a history of early-onset preeclampsia or HELLP syndrome. Methods: We compared the occurence of the factor V Leiden mutation, antiphospholipid antibodies, protein C/S and antithrombin deficiency in 61 women with a history of severe preeclampsia (n = 29) or HELLP syndrome (n = 32) and 61 normotensive women 6 months or longer after delivery.Results: Factor V Leiden mutation was found in 12 cases and 3 controls (20 % vs. 5 %, OR 4.7, 95 % CI 1.4 - 15.8, p = 0.003); IgG or IgM anticardiolipin antibodies in 25 cases and 2 controls (41 % vs. 3 %, OR 20.5, 95 % CI 5.2 - 81.4, p = 0.001); lupus anticoagulant in 33 cases and 2 controls (54 % vs. 3 %, OR 34.8, 95 % CI 8.9 - 134.7, p < 0.001); and protein C/S and antithrombin deficiency 6 cases and 3 controls (10 % vs. 5 %, OR 2.1, 95 % CI 0.6 - 8.0, p = 0.25). Twenty percent of the patients had a history of recurrent spontaneous abortion and 16 % had chronic hypertension.Conclusion: These data indicate a high incidence of inherited and acquired coagulation defects in women with a history of early-onset preeclampsia and HELLP syndrome.

Literatur

• 1 Arnout J, Spitz B, Wittevrongel C, Vanrusselt M, van Assche A, Vermylen J. High dose intravenous immunglobulin treatment of a pregnant patient with an antiphospholipid syndrome: Immunological changes associated with a successful outcome.  Thromb Haemostas. 1994;  71 741-747
• 2 Backos M, Chilocott I, Rai R, Reagan L. Pregnancy complication in women with recurrent miscarriage and antiphospholipid antibodies treated with aspirin and heparin.  Hum Reprod. 1997;  12 61
• 3 Bernstein I M, Ziegler W, Stirewalt W S, Brunnsted J, Ward K. Angitensinogen genotype and plasma volume in multigravid women.  Obstet Gynecol. 1998;  92 171-173
• 4 Bernstein I M, Meyer M C, Osol G, Ward K. Intolerance to volume expansion: A theorized mechanism for the development of preeclampsia.  Obstet Gynecol. 1998;  92 306-308
• 5 Bertina R A, Koeleman B PC, Koster T, Rosendaal F R, Dirven R J, de Ronde H. Mutation in blood coagulation Factor V associated with resistance to activated protein C.  Nature. 1994;  369 64-67
• 6 Birdsall M, Pattison N, Chamley L. Antiphospholipid antibodies in pregnancy.  Austr NZ J Obstet Gynecol. 1992;  32 328-330
• 7 Bokarewa M I, Blombäck M, Bremme K. Phospholipid antibodies and resistance to activated protein C in women with thrombophilia.  Blood Coag Fibrinol. 1995;  6 417-422
• 8 Branch D W, Druzin M, Spinnato J M, Harger J, Mais P, Peaceman A. Randomized, placebo controlled trial of intravenous immunoglobulin (IVIG) in antiphospholipid syndrome (APS) in pregnancy. A progress report.  Lupus. 1996;  5 553
• 9 Branch D W, Silver R M, Backwell J L, Reading J C, Scot J R. Outcome of treated pregnancies in women with antiphospholipid syndrome. An update of the Utah experience.  Obstet Gynecol. 1992;  80 614-620
• 10 Brenner B, Blumenfeld Z. Thrombophilia and fetal loss.  Blood Rev. 1997;  11 72-79
• 11 Clark A L, Branch D W, Silver R M, Harris E N, Pierangelli S, Spinnato J A. Pregnancy complicated by the antiphospholipid syndrome: Outcome intravenous immunoglobuline therapy.  Obstet Gynecol. 1999;  93 437-441
• 12 Dahlbäck B, Carlson M, Svensson P J. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: Prediction of a cofactor to activated protein C.  Proc Nat Acad Sci. 1993;  90 1004-1008
• 13 Dekker G A, de Vries J, Doelitsch P M, Huijgen P C, von Blomberg B M, Jacobs C. Underlying disorders associated with severe early onset preeclampsia.  Am J Obstet Gynecol. 1995;  173 1042-1048
• 14 Faden D, Tinlani A, Tanzi P, Spatola L, Lojascono A, Tarantini M, Balestieri G. Anti β2 Glycoprotein 1 antibodies in a general obstetric population: Preliminary results on the prevalence and correlation with pregnancy outcome.  Europ J Obstet Gynecol Reprod Biol. 1997;  73 37-42
• 15 Harris E N. Syndrome of the black swan.  Br J Rheumatol. 1987;  26 324-326
• 16 Hunt B J, Doughty H A, Majundar G, Copplestone A, Kerslake S, Bouchanan N, Hughes G, Kamashta M. Thromboprophylaxis with low molecular weight heparin in high risk pregnancies.  Thromb Haemostas. 1997;  77 39-43
• 17 Katamo K, Aoki A, Saso H, Ogasawara M, Matsuura E, Yagami Y. Beta 2 glycoprotein 1 dependent anticardiolipin antibodies as a predictor of adverse pregnancy outcome in healthy pregnant women.  Hum Reprod. 1996;  11 509-512
• 18 Kraus M, Zander N, Fickenscher K. Coagulation assay with improved specifity to factor V mutants insensitive to activated protein C.  Thromb Res. 1995;  80 255-264
• 19 Krnic-Barrie S, Riester O, Conner C, Looney St W, Pierangli S S, Harris E V. A retrospective review of 61 patients with antiphospholipid syndrome.  Arch Intern Med. 1997;  157 2101-2108
• 20 Kraus T, Augustin H G, Osmers R, Meden H, Unterhalt M, Kuhn W. Activated protein C resistance and factor V Leiden mutation in patients with hemolysis elevated liver enzymes, low platelets syndrome.  Obstet Gynecol. 1998;  92 457-460
• 21 Kupferminc M J, Eldor A, Steinman N, Many A, Bar-An A, Jaffa A, Fait G, Lessing J B. Increased frequency of genetic thrombophilia in women with complications of pregnancy.  N Engl J Med. 1999;  340 9-13
• 22 Lindoff C, Ingemarsson L, Martinsson G, Segelmark M, Thysell H, Astedt B. Preeclampsia is associated with a reduced response to activated protein C.  Am J Obstet Gynecol. 1997;  176 457-460
• 23 Pattison N S, Chamley L W, Makay E J, Higgins G C. Antiphospholipid antibodies in pregnancy, prevalence and clinical association.  Br J Obstet Gynecol. 1993;  100 909-913
• 24 Peek M J, Nelson Piercy C, Mannig R A, de Swiet M, Letsky E A. Activated protein C resistance in normal pregnancy.  Br J Obstet Gynecol. 1997;  104 1084-1086
• 25 Petri M. Pathogenesis and treatment of the antiphospholipid antibody syndrom.  Adv in Rheumatol. 1997;  81 151-177
• 26 Rand J H, Wu X X, Andree H AM, Lockwood Ch J, Gutler S, Sher J, Harpel P C. Pregnancy loss in the antiphospholipid-antibody syndrome - a possible thrombogenic mechanism.  N Engl J Med. 1997;  337 154-160
• 27 Reece E A, Gabrielli S, Cullen M T, Zheng X Z, Halbin J C, Harris E N. Recurrent adverse pregnancy outcome and antiphospholipid antibodies.  Am J Obstet Gynecol. 1990;  163 162-169
• 28 Rees D C, Cox M, Clagg J B. Distribution of Factor V Leiden.  Lancet. 1995;  346 1133-1134
• 29 Rote N S. Antiphospholipid antibodies and disorders of pregnancy.  J Clin Immunoassay. 1990;  13 34-42
• 30 Schneider D M, Heilmann L, Tempelhoff von G F, Kuse S, Knirsch K, Vogel W. Antiphospholipid antibodies and hematological defects in women with a history of preeclampsia/HELLP and outcome of IVIG treated pregnancies.  Ann Hematol. 1999;  78 55
• 31 Sibai B M, Mercew B, Sarinoglu C. Severe preeclampsia in the second trimester recurrence risk and long term prognosis.  Am J Obstet Gynecol. 1991;  165 1408-1412
• 32 Sibai B M, Sarinoglu C, Mercew B. Eclampsia VII: Pregnancy outcome after eclampsia and longterm prognosis.  Am J Obstet Gynecol. 1992;  166 1757-1763
• 33 Spinnato J A, Clark A L, Pierangelli S, Harris E N. Intravenous immunoglobulin therapy for the antiphospholipid syndrome in pregnancy.  Am J Obstet Gynecol. 1995;  172 690-694
• 34 Sullivan C A, Magann E F, Perry K G, Roberts W E, Blake P G, Martin J N. The recurrence risk of the syndrome of hemolysis elevated liver enzymes and low platelets (HELLP) in subsequent gestations.  Am J Obstet Gynecol. 1994;  171 940-943
• 35 Walker M C, Garner P R, Kelly E J, Rock G A, Reis M D. Changes in activated protein C resistance during normal pregnancy.  Am J Obstet Gynecol. 1997;  177 162-169