Thrombophilia and pregnancy complications: Cause or association?

Journal of Thrombosis and Haemostasis

Volumn 5, Issue SUPPL. 1, 2007, Pages 276-282

  Middeldorp, Saskia ^a  

^a LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Aspirin; Fetal death; Habitual abortion; Haparin; Pregnancy complications; Stillbirth; Thrombophilia

Indexed keywords

ACETYLSALICYLIC ACID; ANTICOAGULANT AGENT; ANTITHROMBIN; BLOOD CLOTTING FACTOR 5 LEIDEN; BLOOD CLOTTING FACTOR 8; CARDIOLIPIN ANTIBODY; ENOXAPARIN; HEPARIN; LOW MOLECULAR WEIGHT HEPARIN; LUPUS ANTICOAGULANT; PHOSPHOLIPID ANTIBODY; PROTEIN C; PROTEIN S; PROTHROMBIN;

ACTIVATED PROTEIN C RESISTANCE; ANTIPHOSPHOLIPID SYNDROME; ANTITHROMBIN DEFICIENCY; CAUSAL ATTRIBUTION; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; DISEASE ASSOCIATION; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG MECHANISM; FETUS DEATH; FETUS WASTAGE; GENE MUTATION; HELLP SYNDROME; HETEROZYGOTE; HIGH RISK PREGNANCY; HUMAN; HYPERCOAGULABILITY; HYPERHOMOCYSTEINEMIA; LOW DRUG DOSE; MATERNAL HYPERTENSION; MONOTHERAPY; NONHUMAN; PATHOPHYSIOLOGY; PREECLAMPSIA; PREGNANCY COMPLICATION; PREGNANCY DISORDER; PREGNANCY OUTCOME; PRIORITY JOURNAL; PROTEIN C DEFICIENCY; PROTEIN S DEFICIENCY; REVIEW; RISK FACTOR; SPONTANEOUS ABORTION; THROMBOPHILIA; TROPHOBLAST; VENOUS THROMBOEMBOLISM;

ANTICOAGULANTS; FEMALE; HUMANS; PREGNANCY; PREGNANCY COMPLICATIONS, HEMATOLOGIC; THROMBOPHILIA;

EID: 34250706405     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/j.1538-7836.2007.02501.x     Document Type: Review

References (75)

1. 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: 295-306.
2. Sanson BJ, Friederich PW, Simioni P, Zanardi S, Huisman MV, Girolami A, et al. The risk of abortion and stillbirth in antithrombin-, protein C-, and protein S-deficient women. Thromb Haemost 1996; 75: 387-8.
3. 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: 913-6.
4. Meinardi JR, Middeldorp S, de Kam PJ, Koopman MMW, van Pampus ECM, Hamulyak K, et al. Increased risk for fetal loss in carriers of the factor V Leiden mutation. Ann Int Med 1999; 130: 736-9.
5. Rey E, Kahn SR, David M, Shrier I. Thrombophilic disorders and fetal loss: A meta-analysis. Lancet 2003; 361: 901-8.
6. Robertson L, Wu O, Langhorne P, Twaddle S, Clark P, Lowe GDO, et al. Thrombophilia in pregnancy: A systematic review. Br J Haematol 2006; 132: 171-96.
7. Coppens M, van Mourik JA, Eckmann CM, Buller HR, Middeldorp S. Current practice of testing for hereditary thrombophilia in The Netherlands. Br J Haematol 2006; 133: 90S (abstract).
8. Egeberg O. Inherited antithrombin III deficiency causing thrombophilia. Thromb Diath Haemorrh 1965; 13: 516-30.
9. Griffin JH, Evatt B, Zimmerman TS, Kleiss AJ, Wideman C. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1981; 68: 1370-3.
10. Comp PC, Esmon CT. Recurrent venous thromboembolism in patients with a partial deficiency of protein S. N Eng J Med 1984; 311: 1525-8.
11. Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Rond, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
12. Dahlback B, Carlsson M, Svensson PJ. 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 Natl Acad Sci U S A 1993; 90: 1004-8.
13. Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88: 3698-703.
14. Falcon CR, Cattaneo M, Panzeri D, Martinelli I, Mannucci PM. High prevalence of hyperhomocyst(e)inemia in patients with juvenile venous thrombosis. Arterioscler Thromb 1994; 14: 1080-3.
15. den Heijer M, Rosendaal FR, Blom HJ, Gerrits WB, Bos GM. Hyperhomocysteinemia and venous thrombosis: A meta-analysis. Thromb Haemost 1998; 80: 874-7.
16. Rosenberg IH, Mulrow CD. Trials that matter: Should we routinely measure homocysteine levels and "treat" mild hyperhomocysteinemia? Ann Int Med 2006; 145: 226-7.
17. den Heijer M, Willems HP, Blom HJ, Gerrits WB, Cattaneo M, Eichinger S, et al. Homocysteine lowering by B vitamins and the secondary prevention of deep-vein thrombosis and pulmonary embolism. A randomized, placebo-controlled, double blind trial. Blood 2007; 109: 139-44.
18. Lijfering W, Coppens M, van der Poel MH, Middeldorp S, Hamulyak K, Bank I, Veeger NJ, Prins MH, Buller HR, van der Meer J. The risk of venous and arterial thrombosis in hyperhomocysteinemia is low and mainly depends on concomitant thrombophilic defects. Thromb Haemost, in press.
19. Ray JG, Shmorgun D, Chan WS. Common C677T polymorphism of the methylenetetrahydrofolate reductase gene and the risk of venous thromboembolism: Meta-analysis of 31 studies. Pathophysiol Haemost Thromb 2002; 32: 51-8.
20. Koster T, Blann AD, Briet E, Vandenbroucke JP, Rosendaal FR. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 1995; 345: 152-5.
21. Kamphuisen PW, Houwing-Duistermaat J, Van Houwelingen HC, Eikenboom JCJ, Bertina RM, Rosendaal FR. Familial clustering of factor VIII and von Willebrand factor levels. Thromb Haemost 1998; 79: 323-7.
22. Bank I, Libourel EJ, Middeldorp S, Hamulyak K, van Pampus ECM, Koopman MMW, et al. Elevated levels of FVIII: C within families are associated with an increased risk for venous and arterial thrombosis. J Thromb Haemost 2005; 3: 79-84.
23. Kamphuisen PW, Lensen R, Houwing-Duistermaat JJ, Eikenboom JC, Harvey M, Bertina RM, et al. Heritability of elevated factor VIII antigen levels in factor V Leiden families with thrombophilia. Br J Haematol 2000; 109: 519-22.
24. Farquharson RG, Jauniaux E, Exalto N. Updated and revised nomenclature for description of early pregnancy events. Hum Reprod 2005; 20: 3008-11.
25. Brown MA, Lindheimer MD, de SM, Van AA, Moutquin JM. The classification and diagnosis of the hypertensive disorders of pregnancy: Statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertens Pregnancy 2001; 20: IX-XIV.
26. Audibert F, Friedman SA, Frangieh AY, Sibai BM. Clinical utility of strict diagnostic criteria for the HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Am J Obstet Gynecol 1996; 175: 460-4.
27. Briskman L. Doctors and witchdoctors: Which doctors are which? I Br Med J (Clin Res Ed) 1987; 295: 1033-6.
28. Briskman L. Doctors and witchdoctors: Which doctors are which?-II. Br Med J (Clin Res Ed) 1987; 295: 1108-10.
29. Hill AB. The environment and disease: Association or causation? Proc R Soc Med 1965; 58: 295-300.
30. Rothman KJ, Greenland S. Causation and causal inference in epidemiology. Am J Public Health 2005; 95 (Suppl. 1): S144-50.
31. Rai R, Regan L. Recurrent miscarriage. Lancet 2006; 368: 601-11.
32. Rosendaal FR. Venous thrombosis: A multicausal disease. Lancet 1999; 353: 1167-73.
33. Hernan MA. A definition of causal effect for epidemiological research. J Epidemiol Community Health 2004; 58: 265-71.
34. Smith GD, Ebrahim S. Mendelian randomization: Prospects, potentials, and limitations. Int J Epidemiol 2004; 33: 30-42.
35. Vandenbroucke JP. When are observational studies as credible as randomized trials? Lancet 2004; 363: 1728-31.
36. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995; 273: 408-12.
37. Juni P, Altman DG, Egger M. Systematic reviews in health care: Assessing the quality of controlled clinical trials. BMJ 2000; 323: 42-6.
38. Bank I, Libourel EJ, Middeldorp S, van Pampus ECM, Koopman MMW, Hamulyak K, et al. Prothrombin 20210A mutation: A mild risk factor for venous thromboembolism but not for arterial thrombotic disease and pregnancy-related complications in a family study. Arch Int Med 2004; 164: 1932-7.
39. Middeldorp S, van der Poel MH, Bank I, Hamulyak K, Libourel EJ, Koopman MMW, et al. Unselected women with elevated levels of factor VIII:c or homocysteine are not at increased risk for obstetric complications. Thromb Haemost 2004; 92: 787-90.
40. Opatrny L, David M, Kahn SR, Shrier I, Rey E. Association between antiphospholipid antibodies and recurrent fetal loss in women without autoimmune disease: A meta-analysis. J Rheumatol 2006; 33: 2214-21.
41. Goddijn M, Leschot NJ. Genetic aspects of miscarriage. Baillieres Best Pract Res Clin Obstet Gynaecol 2000; 14: 855-65.
42. Jauniaux E, Farquharson RG, Christiansen OB, Exalto N. Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage. Hum Reprod 2006; 21: 2116-222.
43. 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: 779-85.
44. Pabinger I, Vormittag R. Thrombophilia and pregnancy outcomes. J Thromb Haemost 2005; 3: 1603-10.
45. Sebire NJ, Regan L, Rai R. Biology and pathology of the placenta in relation to antiphospholipid antibody-associated pregnancy failure. Lupus 2002; 11: 641-3.
46. Quenby S, Mountfield S, Cartwright JE, Whitley GS, Chamley L, Vince G. Antiphospholipid antibodies prevent extravillous trophoblast differentiation. Fertil Steril 2005; 83: 691-8.
47. Bose P, Black S, Kadyrov M, Weissenborn U, Neulen J, Regan L, et al. Heparin and aspirin attenuate placental apoptosis in vitro: Implications for early pregnancy failure. Am J Obstet Gynecol 2005; 192: 23-30.
48. Isermann B, Sood R, Pawlinski R, Zogg M, Kalloway S, Degen JL, et al. The thrombomodulin-protein C system is essential for the maintenance of pregnancy. Nat Med 2003; 9: 331-7.
49. Rai R, Cohen H, Dave M, Regan L. Randomized controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ 1997; 314: 253-7.
50. Farquharson RG, Quenby S, Greaves M. Antiphospholipid syndrome in pregnancy: A randomized, controlled trial of treatment. Obstet Gynecol 2002; 100: 408-13.
51. Noble LS, Kutteh WH, Lashey N, Franklin RD, Herrada J. Antiphospholipid antibodies associated with recurrent pregnancy loss: Prospective, multicenter, controlled pilot study comparing treatment with low-molecular-weight heparin vs. unfractionated heparin. Fertil Steril 2005; 83: 684-90.
52. Empson M, Lassere M, Craig JC, Scott JR. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. Cochrane Database Syst Rev 2005, Issue 2. Art. No.: CD 002859. DOI: 10.1002/14651858.CD002859.pub2.
53. Bates S, Greer IA, Hirsh J, Ginsberg JS. Use of antithrombotic agents during pregnancy. The seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004; 126: 627S-44S.
54. Brenner B. Antithrombotic prophylaxis for women with thrombophilia and pregnancy complications - yes. J Thromb Haemost 2003; 1: 2070-2.
55. Gris JC, Mares P. The long and winding road towards LMWH for pregnancy loss. J Thromb Haemost 2005; 3: 224-6.
56. Middeldorp S. Antithrombotic prophylaxis for women with thrombophilia and pregnancy complications - no. J Thromb Haemost 2003; 1: 2073-4.
57. Lindqvist PG, Merlo J. Low molecular weight heparin for repeated pregnancy loss - is it based on solid evidence? J Thromb Haemost 2005; 3: 221-3.
58. 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: 693-7.
59. 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: 35-44.
60. Grandone E, Brancaccio V, Colaizzo D, Scianname N, Pavone G, Di Minno G, et al. Preventing adverse obstetric outcomes in women with genetic thrombophilia. Fertil Steril 2002; 78: 371-5.
61. 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: 49-54.
62. 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: 433-8.
63. Vossen CY, Preston FE, Conard J, Fontcuberta J, Makris M, van der Meer FJM, et al. Hereditary thrombophilia and fetal loss: A prospective follow-up study. J Thromb Haemost 2004; 2: 592-6.
64. Folkeringa N, Brouwer JL, Korteweg FJ, Veeger NJ, Erwich JJ, Holm JP, et al. Reduction of high fetal loss rate by anticoagulant treatment during pregnancy in antithrombin, protein C or protein S deficient women. Br J Haematol 2007; 136: 656-61.
65. Rai R, Backos M, Elgaddal S, Shlebak A, Regan L. Factor V Leiden and recurrent miscarriage-prospective outcome of untreated pregnancies. Hum Reprod 2002; 17: 442-5.
66. Lindqvist PG, Merlo J. The natural course of women with recurrent fetal loss. J Thromb Haemost 2006; 4: 896-7.
67. Coppens M, Folkeringa N, Teune M, Hamulyak K, van der Meer J, Prins MH, et al. Natural course of the subsequent pregnancy after a single loss in women with and without the factor V Leiden or prothrombin 20210A mutations. J Thromb Haemost, in press.
68. Stray-Pedersen B, Stray-Pedersen S. Etiologic factors and subsequent reproductive performance in 195 couples with a prior history of habitual abortion. Am J Obstet Gynecol 1984; 148: 140-6.
69. Gris JC, Mercier E, Quere I, Lavigne-Lissalde G, Cochery-Nouvellon E, Hoffet M, et al. Low-molecular-weight heparin vs. low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder. Blood 2004; 103: 3695-9.
70. Rodger M. Important publication missing key information. Blood 2004; 104: 3413.
71. Gris JC, Quere I, Dauzat M, Mares P. Response: Thromboprophylaxis for first fetal loss. Blood 2004; 104: 3413-4.
72. DiNisio M, Peters LW, Middeldorp S. Anticoagulants for the treatment of recurrent pregnancy loss in women without antiphospholipid syndrome. Cochrane Database Syst Rev 2005, Issue 2. Art. No.: CD 004734. DOI: 10.1002/14651858.CD004734.pub2.
73. Brenner B, Hoffman R, Carp H, Dulitzky M, Younis J, for the LIVE-ENOX Investigators. 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: 227-9.
74. Middeldorp S. The use of LMWH in pregnancies at risk: New evidence or perception? J Thromb Haemost 2005; 3: 788-9.
75. 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.