Skip to main content
SpringerLink
Log in

Pregnancy Morbidity Associated with Hereditary and Acquired Thrombophilias: Late Obstetric Complications

  • Chapter
  • First Online:
Book cover Disorders of Thrombosis and Hemostasis in Pregnancy

  • 983 Accesses

Abstract

As well as being associated with recurrent miscarriage (RM), antiphospholipid antibodies (aPL) are associated with late placental vascular-mediated pregnancy complications such as severe pre-eclampsia, intrauterine growth restriction (IUGR), abruptio placentae, late fetal loss, and stillbirth. There are also associations between heritable thrombophilias and these late pregnancy complications. Finally, venous thromboembolism (VTE) in pregnancy, as in the non-pregnant state, is linked to thrombophilia. In this review, potential adverse effects of thrombophilia in late pregnancy are discussed. Preliminary data suggest that maternal antithrombotic prophylaxis may result in improved pregnancy outcome in selected cases. Randomized trials are needed to evaluate treatment strategies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Agorastos T, Karavida A, Lambropoulos A, Constantinidis T, Tzitzimikas S, Chrisafi S, et al. Factor V Leiden and prothrombin G20210A mutations in pregnancies with adverse outcome. J Matern Fetal Neonatal Med. 2002;12(4):267–73.

    PubMed  CAS  Google Scholar 

  2. Alfirevic Z, Mousa HA, Martlew V, Briscoe L, ­Perez-Casal M, Toh CH. Postnatal screening for thrombophilia in women with severe pregnancy complications. Obstet Gynecol. 2001;97(5 Pt 1):753–9.

    PubMed  CAS  Google Scholar 

  3. Alfirevic Z, Roberts D, Martlew V. How strong is the association between maternal thrombophilia and adverse pregnancy outcome? A systematic review. Eur J Obstet Gynecol Reprod Biol. 2002;101(1):6–14.

    PubMed  Google Scholar 

  4. Arias F, Romero R, Joist H, Kraus FT. Thrombophilia: a mechanism of disease in women with adverse pregnancy outcome and thrombotic lesions in the placenta. J Matern Fetal Med. 1998;7(6):277–86.

    PubMed  CAS  Google Scholar 

  5. Barker DJ. The fetal and infant origins of adult disease. BMJ. 1990;301(6761):1111.

    PubMed  CAS  Google Scholar 

  6. Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos A-M, Vandvik PO. VTE, thrombophilia, antithrombotic therapy, and pregnancy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence- Based Clinical Practice Guidelines. Chest. 2012;141 (2 Suppl):e691S–736S.

    PubMed  CAS  Google Scholar 

  7. Benedetto C, Marozio L, Salton L, Maula V, Chieppa G, Massobrio M. Factor V Leiden and factor II G20210A in preeclampsia and HELLP syndrome. Acta Obstet Gynecol Scand. 2002;81(12):1095–100.

    PubMed  Google Scholar 

  8. Bloomenthal D, von Dadelszen P, Liston R, Magee L, Tsang P. The effect of factor V Leiden carriage on maternal and fetal health. CMAJ. 2002;167(1):48–54.

    PubMed  Google Scholar 

  9. Bocciolone L, Meroni P, Parazzini F, Tincani A, Radici E, Tarantini M, et al. Antiphospholipid antibodies and risk of intrauterine late fetal death. Acta Obstet Gynecol Scand. 1994;73(5):389–92.

    PubMed  CAS  Google Scholar 

  10. Branch DW, Andres R, Digre KB, Rote NS, Scott JR. The association of antiphospholipid antibodies with severe preeclampsia. Obstet Gynecol. 1989;73(4):541–5.

    PubMed  CAS  Google Scholar 

  11. Branch DW, Scott JR, Kochenour NK, Hershgold E. Obstetric complications associated with the lupus anticoagulant. N Engl J Med. 1985;313(21):1322–6.

    PubMed  CAS  Google Scholar 

  12. Branch DW, Silver R, Pierangeli S, van Leeuwen I, Harris EN. Antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin antibodies in women with recurrent pregnancy loss, fertile controls, and antiphospholipid syndrome. Obstet Gynecol. 1997;89(4):549–55.

    PubMed  CAS  Google Scholar 

  13. Branch DW, Silver RM, Blackwell JL, Reading JC, Scott JR. Outcome of treated pregnancies in women with antiphospholipid syndrome: an update of the Utah experience. Obstet Gynecol. 1992;80(4):614–20.

    PubMed  CAS  Google Scholar 

  14. Bremme K, Ostlund E, Almqvist I, Heinonen K, Blomback M. Enhanced thrombin generation and fibrinolytic activity in normal pregnancy and the puerperium. Obstet Gynecol. 1992;80(1):132–7.

    PubMed  CAS  Google Scholar 

  15. Bremme KA. Haemostatic changes in pregnancy. Best Pract Res Clin Haematol. 2003;16(2):153–68.

    PubMed  Google Scholar 

  16. Brenner B, Hoffman R, Blumenfeld Z, Weiner Z, Younis JS. Gestational outcome in thrombophilic women with recurrent pregnancy loss treated by enoxaparin. Thromb Haemost. 2000;83(5):693–7.

    PubMed  CAS  Google Scholar 

  17. Brenner B, Hoffman R, Carp H, Dulitsky M, Younis J. Efficacy and safety of two doses of enoxaparin in women with thrombophilia and recurrent pregnancy loss: the LIVE-ENOX study. J Thromb Haemost. 2005;3(2):227–9.

    PubMed  CAS  Google Scholar 

  18. Clark P, Brennand J, Conkie JA, McCall F, Greer IA, Walker ID. Activated protein C sensitivity, protein C, protein S and coagulation in normal pregnancy. Thromb Haemost. 1998;79(6):1166–70.

    PubMed  CAS  Google Scholar 

  19. Clark P, Walker ID, Govan L, Wu O, Greer IA. The GOAL study: a prospective examination of the impact of factor V Leiden and ABO(H) blood groups on haemorrhagic and thrombotic pregnancy outcomes. Br J Haematol. 2008;140(2):236–40.

    PubMed  Google Scholar 

  20. Cleary-Goldman J, Bettes B, Robinson JN, Norwitz E, Schulkin J. Thrombophilia and the obstetric patient. Obstet Gynecol. 2007;110(3):669–74.

    PubMed  Google Scholar 

  21. Comp PC, Thurnau GR, Welsh J, Esmon CT. Functional and immunologic protein S levels are decreased ­during pregnancy. Blood. 1986;68(4):881–5.

    PubMed  CAS  Google Scholar 

  22. Conard J, Horellou MH, Van DP, Lecompte T, Samama M. Thrombosis and pregnancy in congenital deficiencies in AT III, protein C or protein S: study of 78 women. Thromb Haemost. 1990;63(2):319–20.

    PubMed  CAS  Google Scholar 

  23. Cumming AM, Tait RC, Fildes S, Yoong A, Keeney S, Hay CR. Development of resistance to activated protein C during pregnancy. Br J Haematol. 1995;90(3):725–7.

    PubMed  CAS  Google Scholar 

  24. De Groot CJ, Bloemenkamp KW, Duvekot EJ, Helmerhorst FM, Bertina RM, Van Der Meer F, et al. Preeclampsia and genetic risk factors for thrombosis: a case–control study. Am J Obstet Gynecol. 1999;181(4):975–80.

    PubMed  Google Scholar 

  25. de Vries JI, Dekker GA, Huijgens PC, Jakobs C, Blomberg BM, van Geijn HP. Hyperhomocysteinaemia and protein S deficiency in complicated pregnancies. Br J Obstet Gynaecol. 1997;104(11):1248–54.

    PubMed  Google Scholar 

  26. de Vries JIP, Van Pampus MG, Hague WM, Bezemer PD, Joosten JH, On Behalf of Fruit Investigators. Low-molecular-weight heparin added to aspirin in the prevention of recurrent early-onset pre-eclampsia in women with inheritable thrombophilia: the FRUIT-RCT. J Thromb Haemost. 2012;10:64–72.

    Google Scholar 

  27. Di SN, Luigi MP, Marco D, Fiorella DN, Silvia D, Clara DM, et al. Pregnancies complicated with antiphospholipid syndrome: the pathogenic mechanism of antiphospholipid antibodies: a review of the literature. Ann N Y Acad Sci. 2007;1108:505–14.

    Google Scholar 

  28. Dizon-Townson DS, Meline L, Nelson LM, Varner M, Ward K. Fetal carriers of the factor V Leiden mutation are prone to miscarriage and placental infarction. Am J Obstet Gynecol. 1997;177(2):402–5.

    PubMed  CAS  Google Scholar 

  29. Dudding T, Heron J, Thakkinstian A, Nurk E, Golding J, Pembrey M, et al. Factor V Leiden is associated with pre-eclampsia but not with fetal growth ­restriction: a genetic association study and meta-analysis. J Thromb Haemost. 2008;6(11):1869–75.

    PubMed  CAS  Google Scholar 

  30. Dudding TE, Attia J. The association between adverse pregnancy outcomes and maternal factor V Leiden genotype: a meta-analysis. Thromb Haemost. 2004;91(4):700–11.

    PubMed  CAS  Google Scholar 

  31. Duley L, Henderson-Smart D, Knight M, King J. Antiplatelet drugs for prevention of pre-eclampsia and its consequences: systematic review. BMJ. 2001;322(7282):329–33.

    PubMed  CAS  Google Scholar 

  32. Facchinetti F, Marozio L, Frusca T, Grandone E, Venturini P, Tiscia GL, et al. Maternal thrombophilia and the risk of recurrence of preeclampsia. Am J Obstet Gynecol. 2009;200(1):46–5.

    PubMed  Google Scholar 

  33. Facco F, You W, Grobman W. Genetic thrombophilias and intrauterine growth restriction: a meta-analysis. Obstet Gynecol. 2009;113(6):1206–16.

    PubMed  Google Scholar 

  34. Franchi F, Biguzzi E, Cetin I, Facchetti F, Radaelli T, Bozzo M, et al. Mutations in the thrombomodulin and endothelial protein C receptor genes in women with late fetal loss. Br J Haematol. 2001;114(3):641–6.

    PubMed  CAS  Google Scholar 

  35. Giavarina D, Mezzena G, Dorizzi RM, Soffiati G. Reference interval of D-dimer in pregnant women. Clin Biochem. 2001;34(4):331–3.

    PubMed  CAS  Google Scholar 

  36. Glueck CJ, Kupferminc MJ, Fontaine RN, Wang P, Weksler BB, Eldor A. Genetic hypofibrinolysis in complicated pregnancies. Obstet Gynecol. 2001;97(1):44–8.

    PubMed  CAS  Google Scholar 

  37. Grandone E, Brancaccio V, Colaizzo D, Scianname N, Pavone G, Di MG, et al. Preventing adverse obstetric outcomes in women with genetic thrombophilia. Fertil Steril. 2002;78(2):371–5.

    PubMed  Google Scholar 

  38. Grandone E, Margaglione M, Colaizzo D, Cappucci G, Paladini D, Martinelli P, et al. Factor V Leiden, C > T MTHFR polymorphism and genetic susceptibility to preeclampsia. Thromb Haemost. 1997;77(6):1052–4.

    PubMed  CAS  Google Scholar 

  39. Grandone E, Margaglione M, Colaizzo D, Cappucci G, Scianname N, Montanaro S, et al. Prothrombotic genetic risk factors and the occurrence of gestational hypertension with or without proteinuria. Thromb Haemost. 1999;81(3):349–52.

    PubMed  CAS  Google Scholar 

  40. Grandone E, Margaglione M, Colaizzo D, Pavone G, Paladini D, Martinelli P, et al. Lower birth-weight in neonates of mothers carrying factor V G1691A and factor II A(20210) mutations. Haematologica. 2002;87(2):177–81.

    PubMed  CAS  Google Scholar 

  41. Greer IA. Procoagulant microparticles: new insights and opportunities in pregnancy loss? Thromb Haemost. 2001;85(1):3–4.

    PubMed  CAS  Google Scholar 

  42. Greer IA. Thrombophilia: implications for pregnancy outcome. Thromb Res. 2003;109(2–3):73–81.

    PubMed  CAS  Google Scholar 

  43. Gris JC, Chauleur C, Faillie JL, Baer G, Mares P, Fabbro-Peray P, et al. Enoxaparin for the secondary prevention of placental vascular complications in women with abruptio placentae. The pilot randomised controlled NOH-AP trial. Thromb Haemost. 2010;104(4):771–9.

    PubMed  CAS  Google Scholar 

  44. Gris JC, Mercier E, Quere I, Lavigne-Lissalde G, Cochery-Nouvellon E, Hoffet M, et al. Low-molecular-weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder. Blood. 2004;103(10):3695–9.

    PubMed  CAS  Google Scholar 

  45. Gris JC, Quere I, Monpeyroux F, Mercier E, Ripart-Neveu S, Tailland ML, et al. Case–control study of the frequency of thrombophilic disorders in couples with late foetal loss and no thrombotic antecedent – the Nimes Obstetricians and Haematologists Study5 (NOHA5). Thromb Haemost. 1999;81(6):891–9.

    PubMed  CAS  Google Scholar 

  46. Hack M, Flannery DJ, Schluchter M, Cartar L, Borawski E, Klein N. Outcomes in young adulthood for very-low-birth-weight infants. N Engl J Med. 2002;346(3):149–57.

    PubMed  Google Scholar 

  47. Higgins JR, Kaiser T, Moses EK, North R, Brennecke SP. Prothrombin G20210A mutation: is it associated with pre-eclampsia? Gynecol Obstet Invest. 2000;50(4):254–7.

    PubMed  CAS  Google Scholar 

  48. Howley HE, Walker M, Rodger MA. A systematic review of the association between factor V Leiden or prothrombin gene variant and intrauterine growth restriction. Am J Obstet Gynecol. 2005;192(3):694–708.

    PubMed  CAS  Google Scholar 

  49. 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(15):1063–6.

    PubMed  CAS  Google Scholar 

  50. Infante-Rivard C, Rivard GE, Yotov WV, Genin E, Guiguet M, Weinberg C, et al. Absence of association of thrombophilia polymorphisms with intrauterine growth restriction. N Engl J Med. 2002;347(1):19–25.

    PubMed  CAS  Google Scholar 

  51. Kaandorp S, Di NM, Goddijn M, Middeldorp S. Aspirin or anticoagulants for treating recurrent miscarriage in women without antiphospholipid syndrome. Cochrane Database Syst Rev. 2009;(1):CD004734.

    Google Scholar 

  52. Kahn SR, Platt R, McNamara H, Rozen R, Chen MF, Genest Jr J, et al. Inherited thrombophilia and preeclampsia within a multicenter cohort: the Montreal Preeclampsia Study. Am J Obstet Gynecol. 2009;200(2):151–9.

    PubMed  Google Scholar 

  53. Kist WJ, Janssen NG, Kalk JJ, Hague WM, Dekker GA, de Vries JI. Thrombophilias and adverse pregnancy outcome – A confounded problem! Thromb Haemost. 2008;99(1):77–85.

    PubMed  CAS  Google Scholar 

  54. Kosmas IP, Tatsioni A, Ioannidis JP. Association of Leiden mutation in factor V gene with hypertension in pregnancy and pre-eclampsia: a meta-analysis. J Hypertens. 2003;21(7):1221–8.

    PubMed  CAS  Google Scholar 

  55. Kruithof EK, Tran-Thang C, Gudinchet A, Hauert J, Nicoloso G, Genton C, et al. Fibrinolysis in pregnancy: a study of plasminogen activator inhibitors. Blood. 1987;69(2):460–6.

    PubMed  CAS  Google Scholar 

  56. Kupferminc MJ, Eldor A, Steinman N, Many A, Bar-Am A, Jaffa A, et al. Increased frequency of genetic thrombophilia in women with complications of pregnancy. N Engl J Med. 1999;340(1):9–13.

    PubMed  CAS  Google Scholar 

  57. Kupferminc MJ, Fait G, Many A, Lessing JB, Yair D, Bar-Am A, et al. Low-molecular-weight heparin for the prevention of obstetric complications in women with thrombophilias. Hypertens Pregnancy. 2001;20(1):35–44.

    PubMed  CAS  Google Scholar 

  58. Kupferminc MJ, Many A, Bar-Am A, Lessing JB, Ascher-Landsberg J. Mid-trimester severe intrauterine growth restriction is associated with a high­prevalence of thrombophilia. BJOG. 2002;109(12):1373–6.

    PubMed  Google Scholar 

  59. Kupferminc MJ, Peri H, Zwang E, Yaron Y, Wolman I, Eldor A. High prevalence of the prothrombin gene mutation in women with intrauterine growth retardation, abruptio placentae and second trimester loss. Acta Obstet Gynecol Scand. 2000;79(11):963–7.

    PubMed  CAS  Google Scholar 

  60. Kutteh WH. 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(5):1584–9.

    PubMed  CAS  Google Scholar 

  61. Laskin CA, Bombardier C, Hannah ME, Mandel FP, Ritchie JW, Farewell V, et al. Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss. N Engl J Med. 1997;337(3):148–53.

    PubMed  CAS  Google Scholar 

  62. Laude I, Rongieres-Bertrand C, Boyer-Neumann C, Wolf M, Mairovitz V, Hugel B, et al. Circulating procoagulant microparticles in women with unexplained pregnancy loss: a new insight. Thromb Haemost. 2001;85(1):18–21.

    PubMed  CAS  Google Scholar 

  63. Leeda M, Riyazi N, de Vries JI, Jakobs C, van Geijn HP, Dekker GA. Effects of folic acid and vitamin B6 supplementation on women with hyperhomocysteinemia and a history of preeclampsia or fetal growth restriction. Am J Obstet Gynecol. 1998;179(1):135–9.

    PubMed  CAS  Google Scholar 

  64. Lima F, Khamashta MA, Buchanan NM, Kerslake S, Hunt BJ, Hughes GR. A study of sixty pregnancies in patients with the antiphospholipid syndrome. Clin Exp Rheumatol. 1996;14(2):131–6.

    PubMed  CAS  Google Scholar 

  65. Lin J, August P. Genetic thrombophilias and preeclampsia: a meta-analysis. Obstet Gynecol. 2005;105(1):182–92.

    PubMed  Google Scholar 

  66. Lindqvist PG, Svensson PJ, Marsaal K, Grennert L, Luterkort M, Dahlback B. Activated protein C resistance (FV:Q506) and pregnancy. Thromb Haemost. 1999;81(4):532–7.

    PubMed  CAS  Google Scholar 

  67. Lockwood CJ. Inherited thrombophilias in pregnant patients: detection and treatment paradigm. Obstet Gynecol. 2002;99(2):333–41.

    PubMed  Google Scholar 

  68. Lynch A, Marlar R, Murphy J, Davila G, Santos M, Rutledge J, et al. Antiphospholipid antibodies in predicting adverse pregnancy outcome. A prospective study. Ann Intern Med. 1994;120(6):470–5.

    PubMed  CAS  Google Scholar 

  69. Many A, Elad R, Yaron Y, Eldor A, Lessing JB, Kupferminc MJ. Third-trimester unexplained intrauterine fetal death is associated with inherited thrombophilia. Obstet Gynecol. 2002;99(5 Pt 1):684–7.

    PubMed  Google Scholar 

  70. Many A, Schreiber L, Rosner S, Lessing JB, Eldor A, Kupferminc MJ. Pathologic features of the placenta in women with severe pregnancy complications and thrombophilia. Obstet Gynecol. 2001;98(6):1041–4.

    PubMed  CAS  Google Scholar 

  71. Martinelli I, Taioli E, Cetin I, Marinoni A, Gerosa S, Villa MV, et al. Mutations in coagulation factors in women with unexplained late fetal loss. N Engl J Med. 2000;343(14):1015–8.

    PubMed  CAS  Google Scholar 

  72. Martinelli P, Grandone E, Colaizzo D, Paladini D, Scianname N, Margaglione M, et al. Familial thrombophilia and the occurrence of fetal growth restriction. Haematologica. 2001;86(4):428–31.

    PubMed  CAS  Google Scholar 

  73. McCowan LM, Craigie S, Taylor RS, Ward C, McLintock C, North RA. Inherited thrombophilias are not increased in “idiopathic” small-for-gestational-age pregnancies. Am J Obstet Gynecol. 2003;188(4):981–5.

    PubMed  Google Scholar 

  74. Mello G, Parretti E, Marozio L, Pizzi C, Lojacono A, Frusca T, et al. Thrombophilia is significantly associated with severe preeclampsia: results of a large-scale, case-controlled study. Hypertension. 2005;46(6):1270–4.

    PubMed  CAS  Google Scholar 

  75. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, De Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295–306.

    PubMed  CAS  Google Scholar 

  76. Morrison ER, Miedzybrodzka ZH, Campbell DM, Haites NE, Wilson BJ, Watson MS, et al. Prothrombotic genotypes are not associated with pre-eclampsia and gestational hypertension: results from a large population-based study and systematic review. Thromb Haemost. 2002;87(5):779–85.

    PubMed  CAS  Google Scholar 

  77. Mousa HA, Alfirevic Z. Do placental lesions reflect thrombophilia state in women with adverse pregnancy outcome? Hum Reprod. 2000;15(8):1830–3.

    PubMed  CAS  Google Scholar 

  78. Muetze S, Leeners B, Ortlepp JR, Kuse S, Tag CG, Weiskirchen R, et al. Maternal factor V Leiden ­mutation is associated with HELLP syndrome in Caucasian women. Acta Obstet Gynecol Scand. 2008;87(6):635–42.

    PubMed  CAS  Google Scholar 

  79. Murphy RP, Donoghue C, Nallen RJ, D’Mello M, Regan C, Whitehead AS, et al. Prospective evaluation of the risk conferred by factor V Leiden and thermolabile methylenetetrahydrofolate reductase polymorphisms in pregnancy. Arterioscler Thromb Vasc Biol. 2000;20(1):266–70.

    PubMed  CAS  Google Scholar 

  80. Nakabayashi M, Yamamoto S, Suzuki K. Analysis of thrombomodulin gene polymorphism in women with severe early-onset preeclampsia. Semin Thromb Hemost. 1999;25(5):473–9.

    PubMed  CAS  Google Scholar 

  81. Nath CA, Ananth CV, DeMarco C, Vintzileos AM. Low birthweight in relation to placental abruption and maternal thrombophilia status. Am J Obstet Gynecol. 2008;198(3):293–5.

    PubMed  Google Scholar 

  82. North RA, Ferrier C, Gamble G, Fairley KF, Kincaid-Smith P. Prevention of preeclampsia with heparin and antiplatelet drugs in women with renal disease. Aust N Z J Obstet Gynaecol. 1995;35(4):357–62.

    PubMed  CAS  Google Scholar 

  83. Nurk E, Tell GS, Refsum H, Ueland PM, Vollset SE. Factor V Leiden, pregnancy complications and adverse outcomes: the Hordaland Homocysteine Study. QJM. 2006;99(5):289–98.

    PubMed  CAS  Google Scholar 

  84. Oshiro BT, Silver RM, Scott JR, Yu H, Branch DW. Antiphospholipid antibodies and fetal death. Obstet Gynecol. 1996;87(4):489–93.

    PubMed  CAS  Google Scholar 

  85. Out HJ, Bruinse HW, Christiaens GC, van Vliet M, De Groot PG, Nieuwenhuis HK, et al. A prospective, controlled multicenter study on the obstetric risks of pregnant women with antiphospholipid antibodies. Am J Obstet Gynecol. 1992;167(1):26–32.

    PubMed  CAS  Google Scholar 

  86. Out HJ, Bruinse HW, Christiaens GC, van Vliet M, Meilof JF, De Groot PG, et al. Prevalence of antiphospholipid antibodies in patients with fetal loss. Ann Rheum Dis. 1991;50(8):553–7.

    PubMed  CAS  Google Scholar 

  87. Pabinger I, Schneider B. Thrombotic risk in hereditary antithrombin III, protein C, or protein S deficiency. A cooperative, retrospective study. Gesellschaft fur Thrombose- und Hamostaseforschung (GTH) Study Group on Natural Inhibitors. Arterioscler Thromb Vasc Biol. 1996;16(6):742–8.

    PubMed  CAS  Google Scholar 

  88. Pasquier E, Bohec C, Mottier D, Jaffuel S, Mercier B, Ferec C, et al. Inherited thrombophilias and unexplained pregnancy loss: an incident case–control study. J Thromb Haemost. 2009;7(2):306–11.

    PubMed  CAS  Google Scholar 

  89. Pattison NS, Chamley LW, McKay EJ, Liggins GC, Butler WS. Antiphospholipid antibodies in pregnancy: prevalence and clinical associations. Br J Obstet Gynaecol. 1993;100(10):909–13.

    PubMed  CAS  Google Scholar 

  90. Polzin WJ, Kopelman JN, Robinson RD, Read JA, Brady K. The association of antiphospholipid antibodies with pregnancies complicated by fetal growth restriction. Obstet Gynecol. 1991;78(6):1108–11.

    PubMed  CAS  Google Scholar 

  91. Preston FE, Rosendaal FR, Walker ID, Briet E, Berntorp E, Conard J, et al. Increased fetal loss in women with heritable thrombophilia. Lancet. 1996;348(9032):913–6.

    PubMed  CAS  Google Scholar 

  92. Prochazka M, Happach C, Marsal K, Dahlback B, Lindqvist PG. Factor V Leiden in pregnancies ­complicated by placental abruption. BJOG. 2003;110(5):462–6.

    PubMed  CAS  Google Scholar 

  93. Prochazka M, Lubusky M, Slavik L, Hrachovec P, Zielina P, Kudela M, et al. Frequency of selected thrombophilias in women with placental abruption. Aust N Z J Obstet Gynaecol. 2007;47(4):297–301.

    PubMed  Google Scholar 

  94. Rai R, Cohen H, Dave M, Regan L. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ. 1997;314(7076):253–7.

    PubMed  CAS  Google Scholar 

  95. Rai RS, Clifford K, Cohen H, Regan L. High prospective fetal loss rate in untreated pregnancies of women with recurrent miscarriage and antiphospholipid antibodies. Hum Reprod. 1995;10(12):3301–4.

    PubMed  CAS  Google Scholar 

  96. Rand JH, Wu XX, Andree HA, Lockwood CJ, Guller S, Scher J, et al. Pregnancy loss in the antiphospholipid-antibody syndrome – a possible thrombogenic mechanism. N Engl J Med. 1997;337(3):154–60.

    PubMed  CAS  Google Scholar 

  97. Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet. 1995;346(8983):1133–4.

    PubMed  CAS  Google Scholar 

  98. Resnik R. Intrauterine growth restriction. Obstet Gynecol. 2002;99(3):490–6.

    PubMed  Google Scholar 

  99. Rey E, Garneau P, David M, Gauthier R, Leduc L, Michon N, et al. Dalteparin for the prevention of recurrence of placental-mediated complications of pregnancy in women without thrombophilia: a pilot randomized controlled trial. J Thromb Haemost. 2009;7(1):58–64.

    PubMed  CAS  Google Scholar 

  100. Rey E, Kahn SR, David M, Shrier I. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet. 2003;361(9361):901–8.

    PubMed  Google Scholar 

  101. Riyazi N, Leeda M, de Vries JI, Huijgens PC, van Geijn HP, Dekker GA. Low-molecular-weight heparin combined with aspirin in pregnant women with thrombophilia and a history of preeclampsia or fetal growth restriction: a preliminary study. Eur J Obstet Gynecol Reprod Biol. 1998;80(1):49–54.

    PubMed  CAS  Google Scholar 

  102. Robertson L, Wu O, Langhorne P, Twaddle S, Clark P, Lowe GD, et al. Thrombophilia in pregnancy: a systematic review. Br J Haematol. 2006;132(2):171–96.

    PubMed  CAS  Google Scholar 

  103. Rodger MA, Betancourt MT, Clark P, Lindqvist PG, Dizon-Townson D, Said J, et al. The association of factor V Leiden and prothrombin gene mutation and placenta-mediated pregnancy complications: a systematic review and meta-analysis of prospective cohort studies. PLoS Med. 2010;7(6):e1000292.

    PubMed  Google Scholar 

  104. Rodger MA, Carrier M, Keely E, Karovitch A, Nimrod C, Walker M, et al. The management of thrombophilia during pregnancy: a Canadian survey. J Obstet Gynaecol Can. 2002;24(12):946–52.

    PubMed  Google Scholar 

  105. Sabadell J, Casellas M, Alijotas-Reig J, Arellano-Rodrigo E, Cabero L. Inherited antithrombin deficiency and pregnancy: maternal and fetal outcomes. Eur J Obstet Gynecol Reprod Biol. 2010;149(1):47–51.

    PubMed  CAS  Google Scholar 

  106. Sanson BJ, Friederich PW, Simioni P, Zanardi S, Hilsman MV, Girolami A, et al. The risk of abortion and stillbirth in antithrombin-, protein C-, and ­protein S-deficient women. Thromb Haemost. 1996;75(3):387–8.

    PubMed  CAS  Google Scholar 

  107. Sarig G, Younis JS, Hoffman R, Lanir N, Blumenfeld Z, Brenner B. Thrombophilia is common in women with idiopathic pregnancy loss and is associated with late pregnancy wastage. Fertil Steril. 2002;77(2):342–7.

    PubMed  Google Scholar 

  108. Scott RA. Anti-cardiolipin antibodies and pre-eclampsia. Br J Obstet Gynaecol. 1987;94(6):604–5.

    PubMed  CAS  Google Scholar 

  109. Sikkema JM, Franx A, Bruinse HW, van der Wijk NG, de Valk HW, Nikkels PG. Placental pathology in early onset pre-eclampsia and intra-uterine growth restriction in women with and without thrombophilia. Placenta. 2002;23(4):337–42.

    PubMed  CAS  Google Scholar 

  110. Stirling Y, Woolf L, North WR, Seghatchian MJ, Meade TW. Haemostasis in normal pregnancy. Thromb Haemost. 1984;52(2):176–82.

    PubMed  CAS  Google Scholar 

  111. van der Molen EF, Verbruggen B, Novakova I, Eskes TK, Monnens LA, Blom HJ. Hyperhomocysteinemia and other thrombotic risk factors in women with placental vasculopathy. BJOG. 2000;107(6):785–91.

    PubMed  Google Scholar 

  112. van Pampus MG, Dekker GA, Wolf H, Huijgens PC, Koopman MM, von Blomberg BM, et al. High prevalence of hemostatic abnormalities in women with a history of severe preeclampsia. Am J Obstet Gynecol. 1999;180(5):1146–50.

    PubMed  Google Scholar 

  113. Vollset SE, Refsum H, Irgens LM, Emblem BM, Tverdal A, Gjessing HK, et al. Plasma total homocysteine, pregnancy complications, and adverse pregnancy outcomes: the Hordaland Homocysteine study. Am J Clin Nutr. 2000;71(4):962–8.

    PubMed  CAS  Google Scholar 

  114. von Kries R, Junker R, Oberle D, Kosch A, Nowak-Gottl U. Foetal growth restriction in children with prothrombotic risk factors. Thromb Haemost. 2001;86(4):1012–6.

    Google Scholar 

  115. Walker ID, Kujovich JL, Greer IA, Rey E, David M, Salmon JE, et al. The use of LMWH in pregnancies at risk: new evidence or perception? J Thromb Haemost. 2005;3(4):778–93.

    PubMed  CAS  Google Scholar 

  116. Wiener-Megnagi Z, Ben-Shlomo I, Goldberg Y, Shalev E. Resistance to activated protein C and the leiden mutation: high prevalence in patients with abruptio placentae. Am J Obstet Gynecol. 1998;179(6 Pt 1):1565–7.

    PubMed  CAS  Google Scholar 

  117. Wilson ML, Goodwin TM, Pan VL, Ingles SA. Molecular epidemiology of preeclampsia. Obstet Gynecol Surv. 2003;58(1):39–66.

    PubMed  Google Scholar 

  118. Younis JS, Samueloff A. Gestational vascular complications. Best Pract Res Clin Haematol. 2003;16(2):135–51.

    PubMed  Google Scholar 

  119. Zoller B, de Garcia FP, Hillarp A, Dahlback B. Thrombophilia as a multigenic disease. Haema­tologica. 1999;84(1):59–70.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Consultant in Obstetrics and Gynaecology, Queen Elizabeth Hospital, South London Healthcare Trust, Stadium Road, Woolwich, London, SE18 4QH, UK

    Sukrutha Veerareddy MRCOG

  2. Consultant in Fetal Medicine, University College London Hospitals, 250 Euston Road, London, NW1 2PG, UK

    Donald Peebles MD, FRCOG

Authors
  1. Sukrutha Veerareddy MRCOG
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Donald Peebles MD, FRCOG
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Donald Peebles MD, FRCOG .

Editor information

Editors and Affiliations

  1. Aberdare Gardens 36, London, NW6 3QA, United Kingdom

    Hannah Cohen

  2. Dept. Obstetrics & Gynaecology, University College Hospital, Chenies Mews 86-96, London, WC1E 6HX, United Kingdom

    Patrick O'Brien

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag London

About this chapter

Cite this chapter

Veerareddy, S., Peebles, D. (2012). Pregnancy Morbidity Associated with Hereditary and Acquired Thrombophilias: Late Obstetric Complications. In: Cohen, H., O'Brien, P. (eds) Disorders of Thrombosis and Hemostasis in Pregnancy. Springer, London. https://doi.org/10.1007/978-1-4471-4411-3_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-4411-3_6

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-4410-6

  • Online ISBN: 978-1-4471-4411-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation