Anticoagulant Therapy in Primary and Secondary Recurrent Pregnancy Losses with Hereditary Thrombophilia and Perinatal Outcomes

Abstract

Objective: To investigate the effect of anticoagulant treatment and perinatal outcomes in patients with primary or secondary recurrent pregnancy loss without cause other than inherited trombophilia. Methods: A total of 143 pregnant patients with recurrent pregnancy loss (≥2 abortus) and had no detected cause other than thrombophilia, were included in the study. Patients with no livebirth history were accepted as primary and patients with at least one livebirth were as secondary recurrent spontaneous aborters (PrimRSAs and SecRSAs). Inherited thrombophilia genetic results of the patients in both groups were compared. The effects of low-molecular weight heparin (LMWH) and low-dose aspirin (LDA) treatments alone or together, livebirth rates and pregnancy outcomes were investigated. Results: Sixty-eight patients were in PrimRSAs and 75 were in SecRSAs. Ages, numbers of total, early and late pregnancy loss of both groups were similar. In PrimRSAs 49 (72.1%) and in SecRSAs 50 (66.6%) patients had three or more inherited thrombophilia genetic mutations. Of 113 patients who used LMWH+LDA during pregnancy 88 (77.6%) had livebirth; however, of 19 patients who used LMWH 6 (31.6%) and of 11 women who used LDA 8 (72.7%) had livebirth. Livebirth rate was significantly higher in patients who used LMWH+LDA together (p=0.001). Livebirth rates were higher in SecRSAs than PrimRSAs irrespective to the anticoagulant treatment (p=0.002). Conclusion: LMWH and LDA treatment together may increase livebirth rates in patients with recurrent pregnancy loss and inherited thrombophilia. Having at least one livebirth of the patients is a good prognostic factor. J Clin Exp Invest 2016; 7 (1): 29-34

Keywords

• Recurrent pregnancy loss,anticoagulant treatment,inherited thrombophilia

Kaynakça

1. 1. Beak KH, Lee EJ, Kim YS. Recurrent pregnancy loss: the key potential mechanisms. Trends Mol Med 2007;13:310- 317.
2. 2. Carson A, Branch W. Management of recurrent early pregnancy loss, Compendium selected publications. American College of Obstetricians and Gynecologists, Washington, DC, 2000:372-383.
3. 3. Sarig G, Klil-Drori A.J, Chap-Marshak D, et al. Activation of coagulation in amniotic fluid during normal human pregnancy. Thromb Res 2011;128:490-495.
4. 4. Szecsi, P.B, Jorgensen M, Klajnbard A, et al. Haemostatic reference intervals in pregnancy. Thromb Haemost 2010;103:718-727.
5. 5. Yokuş O, Balçık Ö.Ş, Albayrak M, et al. Thrombophilic risk factors in women with recurrent abortion. J Clin Exp Invest 2010;1:168-172.
6. 6. Wu O, Robertson L, Twaddle S, et al. Screening for thrombophilia in high-risk situations: a meta-analysis and costeffectiveness analysis. Br J Haematol 2005;131:80-90.
7. 7. Nadar S, Blann AD, Kamath S, et al. Platelet indexes in relation to target organ damage in high-risk hypertensive patients: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). J Am Coll Cardiol 2004;44:415- 422.
8. 8. John H Antiphospholipid syndrome: an overview. Can Med Assoc J 2003;168:1675-1682.

9. 9. Sarig, G., Younis, J. S., Hoffman R., et al. Thrombophilia is common in women with idiopathic pregnancy loss and is associated with late pregnancy wastage. Fertil Steril 2002;77:342-347.
10. 10. Kwak JY, Beer AE, Kim SH, Mantouvalos HP. Immunopathology of the implantation site utilizing monoclonal antibodies to natural killer cells in women with recurrent pregnancy losses. Am J Reprod Immunol 1999;41:91-98.
11. 11. Kwak-Kim J, Yang KM, Gilman-Sachs A. Recurrent pregnancy loss: a disease of inflammation and coagulation. J Obstet Gynaecol Res 2009;35:609-622.
12. 12. Cauchi MN, Coulam CB, Cowchock S, et al.Predictive factors in recurrent spontaneous aborters--a multicenter study. Am J Reprod Immunol 1995;33:165-170.
13. 13. Shakhar K, Ben-Eliyahu S, Loewenthal R, et al. Differences in number and activity of peripheral natural killer cells in primary versus secondary recurrentmiscarriage. Fertil Steril 2003;80: 368-75.
14. 14. Brenner B, Mandel H, Lanir N, et al. Activated protein C resistance can be associated with recurrent fetal loss. Br J Haematol 1997;97:551-554.
15. 15. Rai R, Shlebak A, Cohen H, et al. Factor V Leiden and acquired activated protein C resistance among 1000 women with recurrent miscarriage. Hum Reprod 2001;16:961-95.
16. 16. Raziel A, Kornberg Y, Friedler S, et al. Hypercoagulable thrombophilic defects and hyperhomocysteinemia in patients with recurrent pregnancy loss. Am J Reprod Immunol 2001;45:65-71.
17. 17. Holmes ZR, Regan L, Chilcott I, Cohen H. The C677T MTHFR gene mutation is not predictive of risk for recurrent fetal loss. Br J Haematol 1999;105:98-101
18. 18. Carp HJA, Salomon O, Seidman D, et al. Prevalence of genetic markers for thrombophilia in recurrent pregnancy loss. Human Reprod 2002;17:1633-1637.
19. 19. Vıllanı M, Tıscıa GL, Margaglıone M, et al. Risk of obstetric and thromboembolic complications in family members of women with previous adverse obstetric outcomes carrying common inherited thombophilias. J Thromb Haemostasis 2012;10: 223-228.
20. 20. Lenz B, Samardzija M, Drenjancevic D, et al. The investigation of hereditary and acquired thrombophilia risk factors in the development of complications in pregnancy in Croatian women. J Matern Fetal Neonatal Med 2016;29:264-269.
21. 21. De Carolis S, Ferrazzani S, De Stefano V, et al. Inherited thrombophilia: treatment during pregnancy. Fetal Diagn Ther 2006;21:281-286.
22. 22. Brenner B. Inherited thrombophilia and fetal loss. Curr Opin Hematol 2000;7:290-295.
23. 23. Giancotti A, La Torre R, Spagnuolo A, et al. Efficacy of three different antithrombotic regimens on pregnancy outcome in pregnant women affected by recurrent pregnancy loss. J Matern Fetal Neonatal Med 2012; 25:1191-1194.
24. 24. H. Carp, M. Dolitzkyand, A. Inbal. Thromboprophylaxis improves the live birth rate in women with consecutive recurrent miscarriages and hereditary thrombophilia. J Thromb Haemostasis 2003;1:433-438
25. 25. Elmahashi MO, Elbareg AM, Essadi FM, et al. Low dose aspirin and low-molecular-weight heparin in the treatment of pregnant Libyan women with recurrent miscarriage. BMC Research Notes 2014;7:23.
26. 26. Mutlu I, Mutlu M, Biri A, et al. Effects of anticoagulant therapy on pregnancy outcomes in patients with thrombophilia and previous poor obstetric history. Blood Coagulation & Fibrinolysis 2016; 26:267-273.