THE RELATIONSHIP BETWEEN BAD OBSTETRIC HISTORY AND THROMBOPHILI

Abstract

The aim was to evaluate the relationship of recurring miscarriages and in utero mort fetus cases over 20 weeks of pregnancy (except for those caused by a systemic disease or a known pathology) with thrombophilic conditions. Our study was conducted on the patients who were admitted to our clinic with for follow ups or investigation of recurring pregnancy losses. The included patients had had at least 2 fetal losses over 8 weeks into their pregnancy or at least one loss over the 20th gestational week and gave histories of hypertensive pathologies of pregnancy such as preeclampsia or eclampsia. The control group comprised 81 patients who had at least one pregnancy without any complication or fetal loss histories. In our study, the ratios of Factor V Leiden mutation in the study group (106 cases) and the control group (81 cases) were %12 and %1.3 (p=0.01) respectively. In the patient group, the MTHFR homozygous mutation was seen 3.3 times as much and Factor V Leiden heterozygous gene mutation was determined to be seen 8.3 as much as the control group. There was a significant difference between the study and control groups in terms of Protein C and S activity (p<0.0001 ve p<0.001). In the study group, the detection rate of  Protein C levels <%65 was 5.2 times more(OR 5.2 2.7-12.49), and the Protein S activity was 12.17 times higher than the control group. Thrombophilic cases may play many roles in the pathologies which arise during pregnancies.

Keywords

• thrombophilia,recurring miscarriages

References

1. [12] Mello G, Parretti E, Marozio L, et al. Thrombophilia is significantly associated with severe preeclampsia: results of a large-scale, case-controlled study. Hypertension 2005;46(6):1270-4. https://doi.org/10.1161/01.HYP.0000188979.74172.4d
2. [17] Reznikoff-Etievan MF, Cayol V, Carbonne B, Robert A, Coulet F, Milliez J: Factor V Leiden and G20210A prothrombin mutations are risk factors for very early recurrent miscarriage. BJOG 2001, 108(12):1251-1254
3. [13] 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. doi: 10.1371/journal.pmed.1000292.
4. [19] Pauer HU, Voigt-Tschirschwitz T, Hinney B, et al: Analyzes of three common thrombophilic gene mutations in German women with recurrent abortions. Acta Obstet Gynecol Scand 2003, 82(10):942-7.
5. [15] Deveer R, Engin-Ustun Y, Akbaba E, et al. Association between Pre-eclampsia and inherited thrombophilias. Fetal Pediatr Pathol 2013;32(3):213- 7. doi: 10.3109/15513815.2012.721475.
6. [16] Kjellberg U, van Rooijen M, Bremme K, Hellgren M. Factor V Leiden mutation and pregnancy-related complications. Am J Obstet Gynecol 2010;203(5):469.e1-8. doi: 10.1016/j.ajog.2010.08.011.
7. [22] Osmanagaoglu MA, Topcuoglu K, Ozeren M, Bozkaya H. Coagulation inhibitors in preeclamptic pregnant women. Arch Gynecol Obstet 2005, 271(3):227-30. DOI:10.1007/s00404-003-0596-4
8. [18] Foka ZJ, Lambropouloos AF, Saravelos H, et al: Factor V leiden and prothrombin G20210A mutations, but not methylenetetrahydrofolate reductase C677T, are associated with recurrent miscarriages. Hum Reprod,2000, 15(2):458-62.

9. [1] Preston F, Rosendaal F, Walker ID et al. İncreased fetal loss in women with heritable thrombophilia. The Lancet 1996 ;348(5): 913-916.
10. [20] Sayin M, Varol FG, Sayin NC. Evaluation of natural coagulation inhibitor levels in various hypertensive states of pregnancy. Eur J Obstet Gynecol Reprod Biol. 2005 May. DOI: 10.1016/j.ejogrb.2005.03.020
11. [3] Kupferminc M, Eldor A, Steinman N et al. Increase frequency of genetic thrombophilia in women with complications of pregnancy. N Engl J Med 1999; 340:9-13. DOI: 10.1056/NEJM199901073400102
12. [21] Kupferminc MJ, Fait G, Many A, Gordon D, Eldor A, Lessing JB. Severe preeclampsia and high frequency of genetic thrombophilic mutations. Obstet Gynecol 2000, 96:45-9
13. [5] Mousa HA, Alfirevic Z. Do placental lesions reflect thrombophilia state in women with adversepregnancy outcome? Hum Reprod 2000;15(8):1830-3.
14. [23] Ramalakshmi, B A. Raju, L A. Raman, L. Antithrombin levels in pregnancy induced hypertension. National Med Jour of İndia 1995, 8(2):61-2.
15. [2] Dizon- Townson D, 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; 177:402-5.
16. [8] Kabukcu S, Keskin N, Keskin A, Atalay E. The frequency of factor V Leiden and concomitance of factor V Leiden with prothrombin G20210A mutation and methylene tetrahydrofolate reductase C677T gene mutation in healthy population of Denizli, Aegean region of Turkey. Clin Appl Thromb Hemost 2007;13(2):166-71. DOI:10.1177/1076029606298990
17. [4] Franco C, Walker M, Robertson J, et al. Placental infarction and thrombophilia. Obstet Gynecol 2011;117(4):929-38. doi: 10.1097/AOG.0b013e31820ca040.
18. [10] Dizon-Townson DS, Nelson LM, Easton K, Ward K. The factor V Leiden mutation may predispose women to severe preeclampsia. Am J Obstet Gynecol. 1996 Oct;175(4Pt-1):902-5.
19. [6] Aznar J, Villa P, Espana F, Estelles A, Grancha S, Falco C. Activated protein C resistance phenotype in patients with antiphospholipid antibodies. J Lab Clin Med 1997;130(2):202-8.
20. [7] Lykke JA, Bare LA, Olsen J et al. Thrombophilias and adverse pregnancy outcomes: results from the Danish National Birth Cohort. J Thromb Haemost 2012;10(7):1320-5. doi: 10.1111/j.1538-7836.2012.04773.x.
21. [14] Said JM, Higgins JR, Moses EK, Walker SP, Monagle PT, Brennecke SP. Inherited thrombophilias and adverse pregnancy outcomes: a case-control study in an Australian population. Acta Obstet Gynecol Scand 2012;91(2):250-5. DOI:10.1111/j.1600-0412.2011.01293.x
22. [9] Spina V, Aleandri V, Morini F. The impact of the factor V Leiden mutation on pregnancy. Hum Reprod Update 2000;6(3):301-6.
23. [11] Lin J, August P. Genetic thrombophilias and preeclampsia: a meta-analysis. ObstetGynecol. 2005 Jan;105(1):182-92. DOI:10.1097/01.AOG.0000146250.85561.e9