Early pregnancy loss and inherited thrombophilic states

Czech version

Authors: D. Kašparová; T. Fait
Authors‘ workplace: Gynekologicko-porodnická klinika 1. LF UK a VFN, Praha, přednosta prof. MUDr. A. Martan, DrSc.
Published in: Ceska Gynekol 2009; 74(5): 360-365

Overview

Objective:
Review the literature regarding inherited thrombophilic states and early pregnancy loss.

Design:
Literary review.

Setting:
Department of Gynekology and Obstetrics, 1st Faculty of Medicine, Charles University Prague.

Subject and methods:
Thrombotic risk is increased in normal pregnancy. This risk is further enhanced in women with congenital or aquired thrombophilia. As an adequate placental circulation is dependent on the normal balance procoagulant and anticoagulant mechanism, inherited thrombophilia may be associated with fetal loss. Literary review.

Conclusions:
Placental thrombosis may be final common pathophysiologic pathway in most women with habitus abortions and repeated pregnancy wastage. Preliminary nonrandomized studies suggest a benefit for prophylaxis with unfractioned and low-molecular-weight heparin (LMWH), and prospective randomized trials are in progress to define whether LMWH is effective in preventive pregnancy loss and other gestational vascular complications in women with thrombophilia and previus fetal wastage.

Key words:
inherited trombophilia, pregnancy loss, venous thromboembolism, low-molecular-weight heparin.

Sources

1. Binder, T. Prevence trombembolické nemoci v těhotenství. Gyn po promoci, 2005, 4, s. 8-11.

2. Binder, T. Zabraňuje heparin nežádoucím výsledkům těhotenství spojeným s vrozenou trombofilií? Gyn po promoci, 2008, 1, s. 57-59.

3. Blumenfeld, Z., Brenner, B. Thrombophilia- associated pregnancy wastage. Fertil Steril, 1999, 5, p. 765-775.

4. Brenner, B., Kupferminc, B. Inherited thrombophilia and poor pregnancy outcome. Best Pract Res Clin Obstet Gynec, 2003, 3, p. 427-439.

5. Brenner, B., Blumenfeld, B. Thrombophilia and fetal loss. Blood Rev, 1997, 97, p. 551-554.

6. Brenner, B., Hofman, R., Blumenfeld, Z., et al. Gestational outcome in thrombophilic women with recurrent pregnancy loss treted by enoxaparin. Thromb Haemost, 2000, 83, p. 693-697.

7. Brenner, B., Mandel, H., Lanir, N., et al. Activated protein C resistancecan be associated with recurrent fetal loss. Brit J Haematol, 1997, 97, p. 551-554.

8. Brenner, B., Sarig, G., Weiner, Z., et al. Thrombophilic polymorphisms are common in women with fetal loss without apparent cause. Thromb Haemost, 1999, 82, p. 6-9.

9. Brenner, B., Vulfsons, SL., Lanir, N., et al. Coexistence of familial antiphopolipids syndrome and factor V Leiden- impact of thrombosis diathesis. Brit J Haematol, 1996, 94, p. 166-167.

10. Girling, J., de Swiet, M., et al. Inherited thrombophilia and pregnancy. Curr Opin Obstet Gynecol,1998, 10, p. 135-144.

11. Grandone, E., Brancaccio, V., Colaizzo, BS., et al. Preventing adverse obstetrics outcomes in women with genetic thrombophilia. Fertil Steril, 2002, 78, p. 371-375.

12. Grandone, E., Margaglione, M., Colaizzo, D., et al. Factor V Leiden is assciated with repeated and recurrent unexplained fetal losses. Thromb Haemost, 1997, 77, 822-824.

13. Gris, JC., Mercier, E., Quere, I., et al. Low-molecular-weight heparin versus low-dose aspirin in woman with fetal loss in women with one fetal loss and a constitutional thrombophilic disorder. Blood, 2004, 103, p. 3695-3699.

14. Hajšmanová, Z., Šlechtová, J., Šigutová, P., et al. Průběh těhotenství při dlouhodobém podávání nízkomolekulárního heparinu pro opakované těhotenské ztráty. Čes Gynek, 2008, 5, s. 278-283.

15. Hellgren, M., Svenson, PJ., Daehlback, B., et al. Resistance to activated protein C as a basis for venous thrombembolism associated with pregnancy and oral contraceptives. Am J Obstet Gynecol, 1995, 173, p. 517-522.

16. Kjelberg, U., Andersson, NE., Rosen, S., et al. APC resistance and other haemostatic variablesduring pregnancy and puerperium. Thromb Haemost, 1999, 81, p. 527-531.

17. Krajčovičová, R., Hudeček, R., Kalvodová, J., et al. Diferenciální diagnostika a terapie opakovaných těhotenských ztrát - 1. část, Prakt Gynek, 2007, 4, s. 164-169.

18. Kupferminc, MJ., Eldor, A., Steinman, N., et al. Increased ferquency of genetic thrombophilia in women with complications of pregnancy. N Engl J Med, 1999, 340, p. 9-13.

19. Kupferminc, MJ., Fait, G, Mang, A., et al. A Low molecular weight heparin for the prevention of obstetric complications in women with thrombophilia. Hypertens Pregnancy, 2001, 20, p. 35-44.

20. Martinelli, I., Taioli, J., Cetin, I., et al. Mutations in coagulation factors in women with unexplained late fetal loss. N Engl J Med, 2000, 343, p. 1015-1018.

21. Meinardi, JR., Middeldorp, S., de Kam, PJ., et al. Increased risk for fetal loss in carriers of the factor V Leiden mutation. Ann Intern Med, 1999, p. 736-739.

22. Poort, SW., Rosendal, FR., Reitsma, PH., et al. A common genetic variation in the 3@- untranslated region of the prothrombine gene is associated with elevated plasma prothrombin levels and increase in venous thrombosis. Blood, 1996, 88, p. 3698-3703.

23. Preston, EF., Rosendal, FR., Walker, ID., et al. Increased fetal loss in women with heritable thrombophilia. Lancet, 1996, 348, p. 913-916.

24. Procházka, M. Žilní trombembolie v těhotenství. Gyn po promoci, 2008, 5, s. 19-22.

25. Ridker, PM., Hennekens, CH., Lindpaintner, K., et al. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke and venous thrombosis in apperently healthy men. N Engl J Med, 1995, 332, p. 912-917.

26. Ridker, PM., Miletich, JP., Buring, JE., et al. Factor V Leiden mutation as a risk factor for recurrent pregnancy loss. Ann Intern Med, 1998, 128, p. 1000-1003.

27. Roztočil, A. Opakované těhotenské ztráty: negenetické příčiny. Gyn po promoci, 2007, 5, s. 20-23.

28. Sarig, G., Hoffman, R., Younis, J., et al. Thrombophilia is common in women with pregnancy loss and is associated with late pregnancy wastage. Fertil Steril, 2002, 77, p. 342-347.

29. Scott, JR., Rote, NS., Brand, DW., et al. Immunologic aspects of reccurent abortions and fetal death. Obstet Gynecol, 1987, 70, p. 645-656.

30. Svensson, PJ., Daehlback, B., et al. Resistance to activated protein C as a basis for venous thrombosis. N Engl. J. Med, 1994, 330, 517-522.

31. Vandenbroucke, JP., Koster, T, Briet, T., et al. Increased risk of venous thrombosis in oral-contraceptives users who are carriers of factor V Leiden mutation. Lancet, 1994, 344, 1453-1457.

32. Vossen, CY., Preston, FE., Conard, J., et al. Hereditary thrombophilia and fetal loss: a prospective follow up study. J Thromb Haemost, 2003, 2, p. 592-596.

33. Wramsby, ML., Sten-Lindner, M., Bremme, K., et al. Primary habitual abortions are associated with high frequency of factor V Leiden mutation. Fertil Steril, 2000, 74, p. 987-991.

34. Younis, J. S., Brenner, B., Ohel, G., et al. Activated protein C resistance and factor V Leiden mutation can with first- as well as second- trimestr loss. Am. J. Reprod. Immun., 2000, 43, 31-35

35. Younis, JS., Ohel, G., Brenner, B., et al. The effect of thromboprophylaxis on pregnancy outcomes in patients with reccurent pregnancy loss associated with factor V Leiden mutation. Brit J Obstet Gynaecol, 2000, 107, p. 415-419.