Inherited and Acquired Thrombophilia in Obstetrics

Hemostasis and Thrombosis in Obstetrics & Gynecology

Volumn , Issue , 2011, Pages 67-110

  Paidas, Michael J ^a,b   Han, Christina S ^b   Hossain, Nazli ^c   Lockwood, Charles J ^b  

^a Yale Women and Children's Center for Blood Disorders   (United States)

^b YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c DOW UNIVERSITY OF HEALTH SCIENCES   (Pakistan)

Author keywords

Antiphospholipid antibody syndrome (APAS); Antithrombin Replacement in Preeclampsia; Catastrophic antiphospholipid syndrome (CAPS); Factor V Leiden (FVL); Factor V Leiden and Activated Protein C Resistance; Maternal and Fetal Surveillance During Pregnancy; Methyltetrahydrofolate reductase (MTHFR); Methyltetrahydrofolate Reductase Mutations and Hyperhomocysteinemia; Prothrombin Gene Mutation and Obstetric Complications; Screening and Management of Thrombophilias during Pregnancy; Systemic lupus erythematosus (SLE)

Indexed keywords

EID: 84875718138     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9781444328332.ch5     Document Type: Chapter

References (153)

1. Paidas MJ, Krikun G, Huang SJ, et al. Genomic and proteomic investigation of preimplantation factor's impact on human decidual cells. Am J Obstet Gynecol 2010; 202;459: e1-8.
2. Ness RB, Sibai BM. Shared and disparate components of the pathophysiologies of fetal growth restriction and preeclampsia. Am J Obstet Gynecol 2006; 195(1):40-49. Epub 2006 April 21.
3. Lockwood CJ, Schatz F. A biological model for the regulation of peri-implantational hemostasis and menstruation. J Soc Gynecol Investig 1996; 3(4):159-65. Review.
4. Han CS, Paidas MJ, Lockwood CJ. Clotting disorders. In: High Risk Pregnancy: Management Options, 4th edition edited by David K. James, Philip J. Steer, Carl P. Weiner, Bernard Gonik, Caroline A. Crowther, and Stephen Robson, 4th edn 2010. Elsevier, Philadelphia, PA.
5. Bourjeily G, Paidas M, Khalil H, Rosene-Montella K, Rodger M. Pulmonary embolism in pregnancy. Lancet 2010; 375(9713):500-512.
6. Rodger MA, Paidas M, Claire M, et al. Inherited thrombophilia and pregnancy complications revisited. Obstet Gynecol 2008; 112(2):320-24.
7. Rodger MA, Paidas M. Do thrombophilias cause placenta-mediated pregnancy complications? Semin Thromb Hemost 2007; 33(6):597-603.
8. 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; 4:295-306.
9. Field SL, Brighton TA, McNeil HP, Chesterman CN. Recent insights into antiphospholipid antibody-mediated thrombosis. Baillieres Best Pract Res Clin Haematol 1999; 12:407-22.
10. Rand JH, Wu XX, Andree HA, et al. Pregnancy loss in the antiphospholipidantibody syndrome - a possible thrombogenic mechanism. N Engl J Med 1997; 337:154-60.
11. Girardi G, Redecha P, Salmon JE. Heparin prevents antiphospholipid antibodyinduced fetal loss by inhibiting complement activation. Nat Med 2004; 10:1222-6.
12. Galli M, Luciani D, Bertolini G, Barbui T. Anti-beta 2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome. Blood 2003; 102:2717-23.
13. Wahl DG, Guillemin F, de Maistre E, Perret C, Lecompte T, Thibaut G. Risk for venous thrombosis related to antiphospholipid antibodies in systemic lupus erythematosus - a meta-analysis. Lupus 1997; 6:467-73.
14. Branch DW, Silver RM. Criteria for antiphospholipid syndrome: early pregnancy loss, fetal loss or recurrent pregnancy loss?. Lupus 1996; 5:409-13.
15. 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; 10:3301-4.
16. Hornstein M, Davis O, Massey J, Paulson R, Collins J. Antiphospholipid antibodies and in vitro fertilization success: a meta-analysis. Fertil Steril 2000; 73:330- 333.
17. Stern C, Chamley L, Norris H, Hale L, Baker HW. A randomized, double-blind, placebo-controlled trial of heparin and aspirin for women with in vitro fertilization implantation failure and antiphospholipid or antinuclear antibodies. Fertil Steril 2003; 80:376-83.
18. Opatrny L, David M, Kahn SR, Shrier I, Rey E. Association between antiphospholipid antibodies and recurrent fetal loss in women without autoimmune disease: a metaanalysis. J Rheumatol 2006; 33(11):2214-21. Epub 2006 October 1.
19. Yasuda M, Takakuwa K, Tokunaga A, Tanaka K. Prospective studies of the association between anticardiolipin antibody and outcome of pregnancy. Obstet Gynecol 1995; 86(4 Part 1):555-9.
20. 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.
21. Branch DW, Porter TF, Rittenhouse L, et al. Antiphospholipid antibodies in women at risk for preeclampsia. Am J Obstet Gynecol 2001; 184(5):825-32. Discussion 832-4.
22. Branch DW. Antiphospholipid antibodies and pregnancy: maternal implications. Semin Perinatol 1990; 14:139-46.
23. Cervera R, Khamashta MA, Shoenfeld Y, et al. Euro-Phospholipid Project Group (European Forum on Antiphospholipid Antibodies). Morbidity and mortality in the antiphospholipid syndrome during a 5-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis 2009; 68(9):1428-32. Epub 2008 September 18.
24. Ǵomez-Puerta JA, Cervera R, Espinosa G, et al. Catastrophic antiphospholipid syndrome during pregnancy and puerperium: maternal and fetal characteristics of 15 cases. Ann Rheum Dis 2007; 66(6):740-46.
25. Soares Rolim AM, Castro M, Santiago MB. Neonatal antiphospholipid syndrome. Lupus 2006; 15(5):301-3.
26. Siegert G, Kostka H, Kuhlisch E, et al. Investigation of genotype-dependent differences in factor V activity as well as response to activated protein C by application of different methods. Blood Coagul Fibrinolysis 2001; 12(8):683-90.
27. Bertina RM, Koeleman BP, Koster T, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369:64-7.
28. Franco R, Reitsma P. Genetic risk factors of venous thrombosis. Hum Genet 2001; 109:369-84.
29. Grandone E, Margaglione M, Colaizzo D, et al. Genetic susceptibility to pregnancyrelated venous thromboembolism: roles of factor V Leiden, prothrombin G20210A, and methylenetetrahy-drofolate reductase mutations. Am J Obstet Gynecol 1998; 179:1324-8.
30. Zotz RB, Gerhardt A, Scharf RE. Inherited thrombophilia and gestational venous thromboembolism. Best Pract Res Clin Haematol 2003; 16:243-59.
31. Dizon-Townson D, Miller C, Sibai B, et al.; for the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus. Obstet Gynecol 2005; 106(3):517-24.
32. Infante-Rivard C, Rivard GE, Yotov WV, et al. Absence of association of thrombophilia polymorphisms with intrauterine growth restriction. N Engl J Med 2002; 347:19-25.
33. Wu O, Robertson L, Twaddle S, et al. Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The thrombosis: risk and economic assessment of thrombophilia screening (TREATS) study. Health Technol Assess 2006; 10:1-110.
34. 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. Review.
35. Said JM, Higgins JR, Moses EK, et al. Inherited thrombophilia polymorphisms and pregnancy outcomes in nulliparous women. Obstet Gynecol 2010; 115(1):5-13.
36. Lykke J, Bare L, Langhoff-Roos J, Young B, Devlin J, Paidas MJ. Maternal FVL, but not PGM, is associated with preeclampsia: the Danish national birth cohort (DNBC). 30th annual meeting of the society for maternal fetal medicine, Chicago, Ill. Am J Obstet Gynecol 2009; Supplement to December:S279, abs 776.
37. Rodesch F, Simon P, Donner C, Jauniaux E. Oxygen measurements in endometrial and trophoblastic tissues during early pregnancy. Obstet Gynecol 1992; 80: 283-5.
38. Jaffe R. Investigation of abnormal first-trimester gestations by color Doppler imaging. J Clin Ultrasound 1993; 21:521-6.
39. Watson AL, Skepper JN, Jauniaux E, Burton GJ. Susceptibility of human placental syncytiotrophoblastic mitochondria to oxygen-mediated damage in relation to gestational age. J Clin Endocrinol Metab 1998; 83:1697-705.
40. Roque H, Paidas MJ, Funai EF, Kuczynski E, Lockwood CJ. Maternal thrombophilias are not associated with early pregnancy loss. Thromb Haemost 2004; 91:290-95.
41. Gopel W, Ludwig M, Junge AK, Kohlmann T, Diedrich K, Moller J. Selection pressure for the factor-V-Leiden mutation and embryo implantation. Lancet 2001; 358:1238-9.
42. Preston F, Rosendaal F, Walker I, et al. Increased fetal loss in women with heritable thrombophilia. Lancet 1996; 348:913-16.
43. Dudding T, Attia J. The association between adverse pregnancy outcomes and maternal factor V Leiden genotype: a meta-analysis. Thromb Haemost 2004; 91:700- 711.
44. Rey E, Kahn S, David M, Shrier I. Thrombophilic disorders and fetal loss: a metaanalysis. Lancet 2003; 361:901-8.
45. Gris J, Quéré I, Monpeyroux F, 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; 81:891-9.
46. Kocher O, Cirovic C, Malynn E, et al. Obstetric complications in patients with hereditary thrombophilia identified using the LCx microparticle enzyme immunoassay: a controlled study of 5000 patients. Am J Clin Pathol 2007; 127:68- 75.
47. Kupferminc MJ, Eldor A, Steinman N, et al. Increased frequency of genetic thrombophilia in women with complications of pregnancy. N Engl J Med 1999; 340: 9-13.
48. Lin J, August P. Genetic thrombophilias and preeclampsia: a meta-analysis. Obstet Gynecol 2005; 105:182-92.
49. 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; 21:1221-8.
50. Dudding T, Heron J, Thakkinstian A, et al. Factor V Leiden is associated with preeclampsia but not with fetal growth restriction: a genetic association study and meta-analysis. J Thromb Haemost 2008; 6(11):1869-75.
51. Facchinetti F, Marozio L, Frusca T, et al. Maternal thrombophilia and the risk of recurrence of preeclampsia. Am J Obstet Gynecol 2009; 200(1):46.e1-5.
52. Currie L, Peek M, McNiven M, Prosser I, Mansour J, Ridgway J. Is there an increased maternal-infant prevalence of factor V Leiden in association with severe pre-eclampsia?. BJOG 2002; 109:191-6.
53. van Pampus MG, Wolf H, Koopman MM, Van Den Ende A, Buller HR, Reitsma PH. Prothrombin 20210 G: a mutation and Factor V Leiden mutation in women with a history of severe preeclampsia and (H)ELLP syndrome. Hypertens Pregnancy 2001; 20:291-8.
54. D'Elia AV, Driul L, Giacomello R, et al. Frequency of factor V, prothrombin and methylenetetrahydrofolate reductase gene variants in preeclampsia. Gynecol Obstet Invest 2002; 53:84-7.
55. Kahn SR, Platt R, McNamara H, et al. Inherited thrombophilia and preeclampsia within a multicenter cohort: the Montreal Preeclampsia Study. Am J Obstet Gynecol 2009; 200(2):151.e1-9. Discussion e1-5, Epub 2008 December 13.
56. 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; 179:1565-7).
57. Prochazka M, Happach C, Marsal K, Dahlback B, Lindqvist PG. Factor V Leiden in pregnancies complicated by placental abruption. BJOG 2003; 110:462-6.
58. Procházka M, Lubuský M, Slavík L, et al. Frequency of selected thrombophilias in women with placental abruption. Aust N Z J Obstet Gynaecol 2007; 47(4):297-301.
59. 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; 101:6-14.
60. Martinelli P, Grandone E, Colaizzo D, et al. Familial thrombophilia and the occurrence of fetal growth restriction. Haematologica 2001; 86:428-31.
61. Gerhardt A, Scharf RE, Beckmann MW, et al. Prothrombin and factor V mutations in women with a history of thrombosis during pregnancy and the puerperium. N Engl J Med 2000; 342:374-80.
62. Rosendaal FR, Doggen CJ, Zivelin A, et al. Geographic distribution of the 20210 G to A prothrombin variant. Thromb Haemost 1998; 79(4):706-8.
63. Sottilotta G, Oriana V, Latella C, et al. Genetic prothrombotic risk factors in women with unexplained pregnancy loss. Thromb Res 2006; 117:681-4.
64. Robertson L, Wu O, Langhorne P, et al. Greer IA for the thrombosis: risk and economic assessment of thrombophilia screening (TREATS) study. Thrombophilia in pregnancy: a systematic review. Br J Haematol 2005; 132(2):171-96.
65. Silver RM, Zhao Y, Spong CY, et al. Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (NICHD MFMU) network. Prothrombin gene G20210 A mutation and obstetric complications. Obstet Gynecol 2010; 115(1):14-20.
66. Morrison ER, Miedzybrodzka ZH, Campbell DM, 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: 779-85.
67. Livingston JC, Barton JR, Park V, Haddad B, Phillips O, Sibai BM. Maternal and fetal inherited thrombophilias are not related to the development of severe preeclampsia. Am J Obstet Gynecol 2001; 185:153-7.
68. Larciprete G, Gioia S, Angelucci PA, et al. Single inherited thrombophilias and adverse pregnancy outcomes. J Obstet Gynaecol Res 2007; 33(4):423-30.
69. Franchi F, Cetin I, Todros T, et al. Intrauterine growth restriction and genetic predisposition to thrombophilia. Haematologica 2004; 89:444-9.
70. Verspyck E, Borg JY, Le Cam-Duchez V, et al. Thrombophilia and fetal growth restriction. Eur J Obstet Gynecol Reprod Biol 2004; 113:36-40.
71. Facco F, You W, Grobman W. Genetic thrombophilias and intrauterine growth restriction: a meta-analysis. Obstet Gynecol 2009; 113(6):1206-16.
72. Botto LD, Yang Q. 5, 10-Methylenetetrahydrofolate reductase (MTHFR) gene variants and congenital anomalies. Am J Epidemiol 2000; 151(9):862-77.
73. Peng F, Labelle LA, Rainey BJ, Tsongalis GJ. Single nucleotide polymorphisms in the methylenetetrahydrofolate reductase gene are common in US Caucasian and Hispanic American populations. Int J MolMed 2001; 8:509-11.
74. den Heijer M, Rosendaal FR, Blom HJ, Gerrits WB, Bos GM. Hyperhomocysteinemia and venous thrombosis: a meta-analysis. Thromb Haemost 1998; 80:874-7.
75. Eichinger S. Homocysteine, vitamin B6 and the risk of recurrent venous thromboembolism. Pathophysiol Haemost Thromb 2003; 33:342-4.
76. Domagala TB, Adamek L, Nizankowska E, Sanak M, Szczeklik A. Mutations C677 T and A1298 C of the 5,10-methylenetetrahydrofolate reductase gene and fasting plasma homocysteine levels are not associated with the increased risk of venous thromboembolic disease. Blood Coagul Fibrinolysis 2002; 13:423-31.
77. McColl MD, Ellison J, Reid F, Tait RC, Walker ID, Greer IA. Prothrombin 20210G-A, MTHFR C677 T mutations in women with venous thromboembolism associated with pregnancy. BJOG 2000; 107:565-9.
78. Nelen WL, Blom HJ, Steegers EA, den Heijer M, Eskes TK. Hyperhomocysteinemia and recurrent early pregnancy loss: a meta-analysis. Fertil Steril 2000; 74: 1196-9.
79. Nurk E, Tell GS, Refsum H, Ueland PM, Vollset SE. Associations between maternal methylenetetrahydrofolate reductase polymorphisms and adverse outcomes of pregnancy: the Hordaland Homocysteine Study. Am J Med 2004; 117:26- 31.
80. Falcao S, Bisotto S, Gutkowska J, Lavoie JL. Hyperhomocysteinemia is not sufficient to cause preeclampsia in an animal model: the importance of folate intake. Am J Obstet Gynecol. 2009; 200(2):198.e1-5.
81. Also-Rallo E, Lopez-Quesada E, Urreizti R, et al. Polymorphisms of genes involved in homocysteine metabolism in preeclampsia and in uncomplicated pregnancies. Eur J Obstet Gynecol Reprod Biol 2005; 120(1):45-52.
82. Ananth CV, Peltier MR, De Marco C, et al. New Jersey-Placental Abruption Study Investigators. Associations between 2 polymorphisms in the methylenetetrahydrofolate reductase gene and placental abruption. Am J Obstet Gynecol 2007; 197(4):385.e1-7.
83. Ray JG, Laskin CA. Folic acid and homocyst(e)ine metabolic defects and the risk of placental abruption, pre-eclampsia and spontaneous pregnancy loss: a systematic review. Placenta 1999; 20:519-29.
84. Goodwin AJ, Rosendaal FR, Kottke-Marchant K, Bovill EG. A review of the technical, diagnostic, and epidemiologic considerations for protein S assays. Arch Pathol Lab Med 2002; 126:1349-66.
85. Paidas MJ, Ku DH, Lee MJ, et al. Protein Z, protein S levels are lower in patients with thrombophilia and subsequent pregnancy complications. J Thromb Haemost 2005; 3:497-501.
86. Saade GR, McLintock C. Inherited thrombophilia and stillbirth. Semin Perinatol 2002; 26(1):51-69.
87. Friederich PW, Sanson BJ, Simioni P, et al. Frequency of pregnancy related venous thromboembolism in anticoagulant-deficient women. Ann Intern Med 1996; 125:955-60.
88. Sanson BJ, Friederich PW, Simioni P, et al. The risk of abortion and stillbirth in antithrombin, protein C, and protein S deficient women. Thromb Haemost 1996; 75:387-8.
89. Patnaik MM, Moll S. Inherited antithrombin deficiency: a review. Haemophilia 2008; 14(6):1229-39. Review.
90. Maclean PS, Tait RC. Hereditary and acquired antithrombin deficiency: epidemiology, pathogenesis and treatment options. Drugs 2007; 67(10):1429-40.
91. Duhl AJ, Paidas MJ, Ural SH, et al. Pregnancy and Thrombosis Working Group. Antithrombotic therapy and pregnancy: consensus report and recommendations for prevention and treatment of venous thromboembolism and adverse pregnancy outcomes. Am J Obstet Gynecol 2007; 197(5):457.e1-21.
92. Weiner CP, Kwaan HC, Xu C, Paul M, Burmeister L, Hauck W. Antithrombin III activity in women with hypertension during pregnancy. Obstet Gynecol 1985; 65(3):301-6.
93. Weiner CP, Brandt J. AT levels in normal pregnancy. Obstet Gynecol 1980; 56:601.
94. Marietta M, Simoni L, Pedrazzi P, Facchini L, D'Amico R, Facchinetti F. Antithrombin plasma levels decrease is associated with preeclampsia worsening. Int J Lab Hematol 2009; 31(2):227-32.
95. Weenink GH, Treffers PE, Vijn P, Smorenberg-Schoorl ME, Ten Cate JW. Antithrombin III levels in preeclampsia correlate with maternal and fetal morbidity. Am J Obstet Gynecol 1984; 148(8):1092-7.
96. Castro MA, Goodwin TM, Shaw KJ, Ouzounian JG, McGehee WG. Disseminated intravascular coagulation and antithrombin III depression in acute fatty liver of pregnancy. Am J Obstet Gynecol 1996; 174(1 Part 1):211-16.
97. Catov JM, Bodnar LM, Hackney D, Roberts JM, Simhan HN. Activation of the fibrinolytic cascade early in pregnancy among women with spontaneous preterm birth. Obstet Gynecol 2008; 112(5):1116-22.
98. Krause M, Sonntag B, Klamroth R, et al. Lipoprotein (a) and other prothrombotic risk factors in Caucasian women with unexplained recurrent miscarriage. Results of a multicentre case-control study. Thromb Haemost 2005; 93(5):867- 71.
99. Jaslow CR, Carney JL, Kutteh WH. Diagnostic factors identified in 1020 women with two versus three or more recurrent pregnancy losses. Fertil Steril 2009.
100. Buller HR, et al. Severe antithrombin III deficiency in a patient with pre-eclampsia. Observations on the effect of human AT III concentrate transfusion. Scand J Haematol 1980; 25(1):81-6 ABS only avail.
101. Terao T, Kobayashi T, Imai N, Oda H, Karasawa T. Pathological state of the coagulatory and fibrinolytic system in preeclampsia and the possibility of its treatment with AT III concentrate. Asia Oceania J Obstet Gynaecol 1989; 15(1):25-32. ABS only available.
102. Nakabayashi M, Asami M, Nakatani A. Efficacy of antithrombin replacement therapy in severe early-onset preeclampsia. Semin Thromb Hemost 1999; 25(5):463-6. ABS only avail.
103. Kobayashi T, Terao T, Ikenoue T, et al. BI 51 017 Study Group. Treatment of severe preeclampsia with antithrombin concentrate: results of a prospective feasibility study. Semin Thromb Hemost 2003; 29(6):645-52.
104. Kobayashi T, Terao T, Ikenoue T, Kajiwara Y, Maki M. Antithrombin therapy for preeclampsia. Biomed Prog 2003; 16:72-77.
105. Kobayashi T. Antithrombin abnormalities and perinatal management. Curr Drug Targets 2005; 6:559-66.
106. Maki M, Kobayashi T, Terao T, et al. Antithrombin therapy for severe preeclampsia: results of a double-blind, randomized, placebo-controlled trial. BI51.017 study group. Thromb Haemost 2000; 84(4):583-90.
107. Paternoster DM, Fantinato S, Manganelli F, Milani M, Nicolini U, Girolami A. Efficacy of AT in pre-eclampsia: a case-control prospective trial. Thromb Haemost 2004; 91(2):283-9.
108. Sibai BM. Maternal and uteroplacental hemodynamics for the classification and prediction of preeclampsia. Hypertension 2008; 52(5):805-6.
109. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet 2008; 371(9606):75-84.
110. Duley L, Henderson-Smart DJ, Meher S, King JF. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev 2007; (2):CD004659. Review.
111. Urban G, Vergani P, Tironi R, et al. Antithrombotic prophylaxis in multiparous women with preeclampsia or intrauterine growth retardation in antecedent pregnancy. Int J Fertil Womens Med 2007; 52(2-3):59-67.
112. Rey E, Garneau P, David M, 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.
113. Haddad B, Deis S, Goffinet F, Paniel BJ, Cabrol D, Siba BM. Maternal and perinatal outcomes during expectant management of 239 severe preeclamptic women between 24 and 33 weeks' gestation. Am J Obstet Gynecol 2004; 190(6):1590- 95.
114. Lykke JA, Langhoff-Roos J, Sibai BM, Funai EF, Triche EW, Paidas MJ. Hypertensive pregnancy disorders and subsequent cardiovascular morbidity and type 2 diabetes mellitus in the mother. Hypertension. 2009; 53(6):944-51.
115. Lykke J, Paidas MJ, Langhoff-Roos J. Recurring complications in second pregnancy. Obstet Gynecol 2009; 113(6):1217-24.
116. Morange PE, Henry M, Tregouet D, et al. The A844G polymorphism in the PAI- 1 gene is associated with a higher risk of venous thrombosis in factor V Leiden carriers. Arterioscler Thromb Vasc Biol 2000; 20:1387-91.
117. Kohler HP, Grant PJ. Plasminogen activator inhibitor type 1 and coronary heart disease. N Engl J Med 2000; 342:1792-801.
118. Buchholz T, Lohse P, Rogenhofer N, Kosian E, Pihusch R, Thaler CJ. Polymorphisms in the ACE and PAI-1 genes are associated with recurrent spontaneous miscarriages. Hum Reprod 2003; 18:2473-7.
119. Varela ML, Adamczuk YP, Forastiero RR, et al. Major and potential prothrombotic genotypes in a cohort of patients with venous thromboembolism. Thromb Res 2001; 104:317-24.
120. Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Miletich JP. Arterial and venous thrombosis is not associated with the 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor gene in a large cohort of US men. Circulation 1997; 95:59-62.
121. Francis CW. Plasminogen activator inhibitor-1 levels and polymorphisms. Arch Pathol Lab Med 2002; 126(11):1401-4.
122. Tsantes AE, Nikolopoulos GK, Bagos PG, et al. Association between the plasminogen activator inhibitor-1 4G/5G polymorphism and venous thrombosis. A metaanalysis. Thromb Haemost 2007; 97(6):907-13.
123. Zöller B, Garcia de Frutos P, Dahlbäck B. A common 4G allele in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene as a risk factor for pulmonary embolism and arterial thrombosis in hereditary protein S deficiency. Thromb Haemost 1998; 79:802-7.
124. Glueck CJ, Phillips H, Cameron D, et al. The 4G/4G polymorphism of the hypofibrinolytic plasminogen activator inhibitor type 1 gene: An independent risk factor for serious pregnancy complications. Metabolism 2000; 49:845-52.
125. Hefler L, Jirecek S, Heim K, et al. Genetic polymorphisms associated with thrombophilia and vascular disease in women with unexplained late intrauterine fetal death: a multicenter study. J Soc Gynecol Investig 2004; 11(1):42-4.
126. Wolf CE, Haubelt H, Pauer HU, et al. Recurrent pregnancy loss and its relation to FV Leiden, FII G20210 A and polymorphisms of plasminogen activator and plasminogen activator inhibitor. Pathophysiol Haemost Thromb 2003; 33:134-7.
127. Dossenbach-Glaninger A, van Trotsenburg M, Dossenbach M, et al. Plasminogen activator inhibitor 1 4G/5G polymorphism and coagulation factor XIII Val34Leu polymorphism: impaired fibrinolysis and early pregnancy loss. Clin Chem 2003; 49:1081-6.
128. Yamada N, Arinami T, Yamakawa-Kobayashi K, et al. The 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene is associated with severe preeclampsia. J Hum Genet 2000; 45:138-41
129. Scifres CM, Macones GA. The utility of thrombophilia testing in pregnant women with thrombosis: fact or fiction? Am J Obstet Gynecol 2008; 199(4):344.e1-7. Epub 2008 Jun 24.
130. Bates SM, Greer IA, Pabinger I, Sofaer S, Hirsh J; American College of Chest Physicians. Venous thromboembolism, thrombophilia, antithrombotic therapy, and pregnancy: American college of chest physicians evidence-based clinical practice guidelines (8th Edition). Chest 2008; 133(Suppl. 6):844S-86S.
131. Kaandorp SP, Goddijn M, van der Post JA, et al. Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. N Engl J Med 2010; 362(17):1586-96.
132. Clark P, Walker ID, Langhorne P, et al. Scottish Pregnancy Intervention Study (SPIN): a multicenter, randomized controlled trial of low-molecular-weight heparin and low-dose aspirin in women with recurrent miscarriage. Blood 2010;115(21):4162-67.
133. Rodger MA, Betancourt MT, Clark P, 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.
134. Ziakas PD, Pavlou M, Voulgarelis M. Heparin treatment in antiphospholipid syndrome with recurrent pregnancy loss: a systematic review and meta-analysis. Obstet Gynecol 2010;115(6):1256-62.
135. Cowchock S, Reece EA. 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; 176:10991100.
136. Tulppala M, MarttunenM, Soderstrom-Anttila V, et al. Low-dose aspirin in prevention of miscarriage in women with unexplained or autoimmune related recurrent miscarriage: effect on prostacyclin and thromboxane A2 production. Hum Reprod 1997; 12:15671572.
137. Pattison NS, Chamley LW, Birdsall M, et al. Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome? A randomized controlled trial. Am J Obstet Gynecol 2000; 183:10081012.
138. Laskin CA, Bombardier C, HannahME, et al. Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss. NEngl J Med 1997; 337:14853.
139. Rai R, Cohen H, Dave M, et al. Randomised controlled trial of aspirin and aspirinplus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies(or antiphospholipid antibodies). BMJ 1997; 314:25357.
140. 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; 174:158489.
141. Kutteh WH, Ermel LD. A clinical trial for the treatment of antiphospholipid antibody-associated recurrent pregnancy loss with lower dose heparin and aspirin. Am J Reprod Immunol 1996; 35:402407.
142. Franklin RD, Kutteh WH. Antiphospholipid antibodies (APA) and recurrent pregnancy loss: treating a unique APA positive population. Hum Reprod 2002; 17:298185.
143. 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; 48:728731.
144. Farquharson RG, Quenby S, Greaves M. Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. Obstet Gynecol 2002; 100:408413.
145. Stephenson MD, Ballem PJ, Tsang P, et al. Treatment of antiphospholipid antibody syndrome (APS) in pregnancy: a randomized pilot trial comparing low molecular weight heparin to unfractionated heparin. J Obstet Gynaecol Can 2004; 26:729734.
146. Noble LS, Kutteh WH, Lashey N, et al. Antiphospholipid antibodies associated with recurrent pregnancy loss: prospective, multicenter, controlled pilot study comparing treatment with low-molecular-weight heparin versus unfractionated heparin. Fertil Steril 2005; 83:684690
147. Kupferminc MJ, Fait G, Many A, et al. Low-molecularweight heparin for the prevention of obstetric complications in women with thrombophilias. Hypertens Pregnancy 2001; 20:3544.
148. Brenner B, Hoffman R, Blumenfeld Z, et al. Gestational outcome in thrombophilic women with recurrent pregnancy loss treated by enoxaparin. Thromb Haemost 2000; 83:693697.
149. Carp H, Dolitzky M, Inbal A. Thromboprophylaxis improves the live birth rate in women with consecutive recurrent miscarriages and hereditary thrombophilia. J Thromb Haemost 2003; 1:433438.
150. Tzafettas J, Petropoulos P, Psarra A, et al. Early antiplatelet and antithrombotic therapy in patients with a history of recurrent miscarriages of known and unknown aetiology. Eur J Obstet Gynaecol Reprod Biol 2005; 120:2226
151. Gris JC, Mercier E, Quere I, et al. Low-molecular-weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder. Blood 2004; 103:36953699.
152. Brenner B, Bar J, Ellis M, et al. Effects of enoxaparin on late pregnancy complications and neonatal outcome in women with recurrent pregnancy loss and thrombophilia: results from the Live-Enox study. Fertil Steril 2005a; 84:770773.
153. Brenner B, Hoffman R, Carp H, et al. Efficacy and safety of two doses of enoxaparin in women with thrombophilia and recurrent pregnancy loss: the LIVE-ENOX study. J Thromb Haemost 2005b; 3:227229.