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Thrombophilia in complicated pregnancies

Year 2013, , 497 - 502, 01.12.2013
https://doi.org/10.5799/ahinjs.01.2013.04.0332

Abstract

Objective: To investigate the incidence and etiology of pregnancy complications associated with thrombophilic factors. Methods: Fifty-four patients with complicated pregnancy and 40 healthy pregnant subjects were included the study. Factor V Leiden (FVL) mutation, protein S, protein C, anti-thrombin deficiency levels were investigated. Results: Of the 54 patients with complicated pregnancy, 29 had preeclampsia, 18 had intra uterine growth retardation, and 7 had intrauterine fetal loss. The most common defect was FVL mutation. FVL mutations in patient group and the control group were 27.2% and 10%, respectively, which were statistically significant. The protein S, protein C, and anti-thrombin deficiencies were found higher in the patient group compared to control (p>0.05 for each). Conclusion: FVL mutation was found higher in patient group compared to the control group, Protein C deficiency and anti-thrombin deficiency were related to preeclampsia but not other pregnancy complications. Clinicians should take into account the thrombophilia in complicated pregnancy, especially preeclampsia. J Clin Exp Invest 2013; 4 (4): 497-502

References

  • De Sefano V, Finazzi G, Mannucci PM. Inherited throm- bophilia: Patogenesis, Clinical syndromes and man- agement. Blood 1996;87:3531-3444.
  • Girling J, de Swiet M. Inherited thrombofilia and pregnan- cy. Curr Opin Obstet Gynecol 1998;10:135-144.
  • Griffin J, Evatt B, Zimmerman T, et al. Deficiency of pro- tein C in congenital thrombotic disease. J Clin Invest 1981;68:1370-1373.
  • Dahlback B, Carlsson M, Svensson PJ. Familial throm- bophilia due to a previously unrecognised mechanism characterized by poor anticoagulant response to activat- ed Protein C: Prediction of a cofactor to activated Protein C. Proc Natl Acad Sci USA 1993; 90:1004-1008.
  • Price DT, Ridker PM. Factor V Leiden mutation and the risks for thromboembolic diseases: a clinical perspec- tive. Ann Intern Med 1997;127:895-903.
  • Griffin JH, Evatt B, Wideman C, et al. Anticoagulant pro- tein C pathway defective in majority thrombophilic pa- tients. Blood 1993;82:1989-1993.
  • Higgins JR, Walshe JJ, Darling MR, Norris L, Bonnar J. Hemostasis in the uteroplacental and peripheral circu- lations in normotensive and pre-eclamptic pregnancies. Am J Obstet Gynecol 1998;179:520-526.
  • McLintock C, Horth RA, Dekker G. Inherited trrombo- philias: Implications for pregnancy associated venous thromboembolism nd obstetric complications. Curr Probl Obstet Gynecol Fertil 2001;24:109-152.
  • Mousa HA, Alfirec Z. Do placental lesions reflect thrombo- philia state in women with adverse pregnancy outcome? Hum Reprod 2000;15:1830-1833.
  • De Stefano V, Chiusolo P, Paciaroni K, et al. Epidemi- ology of factor V Leiden: clinical implications. Semin Thromb Hemost 1998;24:367-379.
  • Deren Ö, Baykal C, Al A, et al. Nedeni açıklanamayan gebelik komplikasyonlarında trombofilik hastalıkların rolü. Jinekoloji ve Obstetrik Bülteni 2000;9:18-22.
  • Özbek U, Tangün Y. Frequency of factor V Leiden (Arg- 506Gln) in Turkey. Br J Haematol 1997;97:504-505.
  • Yokuş O, Balçık ÖŞ, Albayrak M, et al. Thrombophilic risk factors in women with recurrent abortion. J Clin Exp Invest 2010;1:168-172.
  • Dizon-Townson DS, Nelson LM, Easton K, et al. The fac- tor V Leiden mutation may predispose women to severe preeclampsia. Am J Obstet Gynecol 1996 ;175:902-905.
  • Nagy B, Toth T, Rigo J Jr, et al. Detection of factor V leiden mutation in severe pre-eclamptic Hungarian Women. Clin Genet 1998;53:478-481.
  • Lin J, August P. Genetic thrombophilias and preeclamp- sia: a meta-analysis. Obstet Gynecol 2005;105:182-192.
  • Dudding TE, Attia J. The association between adverse pregnancy outcomes and maternal factor V Leiden gen- otype: a meta-analysis. Thromb Haemost 2004;91:700- 711.
  • Livingston JC, Barton JR, Park V, et al. Maternal and fetal inherited thrombophilias are not related to the de- velopment of severe preeclampsia. Am J obstet Gynecol 2001;185:153-157.
  • Paternoster DM, Stella A, Simioni P, et al. Activated pro- tein C resistance in normal and pre-eclamptic pregnan- cies. Gynecol Obstet Invest 2002;54:145-149.
  • Osmanagaoglu MA, Topcuoglu K, Ozeren M, et al. Co- agulation inhibitors in preeclamptic pregnant women. Arch Gynecol Obstet 2005;271:227-230.
  • 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;123:183-187
  • Faught W, Garner PJ, Jones G, et al. Changes in protein C protein S levels in normal pregnancy. Am J Obstet Gy- necol 1995;172:147-150.
  • Dekker GA, de Vries JI, Doelitzsch PM, et al. Underlying disorders associated with severe early-onset preeclam- sia. Am J Obstet Gynecol 1995;173:1042-1048.
  • Kupferminc MJ, Fait G, Many A, et al. Severe pre- eclampsia and high frequency of genetic thrombophilic mutations. Obstet Gynecol 2000;96:45-49.
  • Finazzi G, Caccia R, Barbui T. Different prevalence of thromboembolism in the subtypes of congenital anti- thrombin 3 deficiency: Review of 404 cases. Thromb Haemost 1987;58:1094-1099.
  • Gebhard GS, Hall DR. Inherited and acquired throm- bophilias and poor pregnancy outcome: should we be treating with heparin? Curr Opin Obstet Gynecol 2003;15:501-506.
  • Mc Cowan LM, Craigie S, Taylor RS, et al. Inherited Thrombophilias are not increased in ‘idiopathic’ small for gestational age pregnancies. Am J Obstet Gynechol 2003;188:81-985.
  • Howley HE, Walker M, Rodger MA. A systematic review of the association between factor V Leiden or prothrom- bin gene variant and intrauterine growth restriction. Am J Obstet Gynecol. 2005;192:694-708.
  • Kupferminc M, Eldor A, Steinman N, et al. Increase fre- quency of genetic thrombophilia in women with compli- cations of pregnancy. N Engl J Med 1999;340:9-13.
  • de Vries JIP, Dekker GA, Huijgens PC, et al. Hyperho- mocysteinaemia and protein S deficiency in complicated pregnancies. Br J Obstet Gynaecol 1997;104:1248- 1254.
  • Alonso A, Soto I, Urgelles MF, et al. Acquired and in- herited thrombophilia in women with unexplained fetal losses. Am J Obstet Gynecol 2002;187:1337-1342.
  • Sarig G, Younis JS, 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.
  • Preston FE, Rosendaal FR, Walker ID, et al. Increased fetal loss in women with heritable thrombophilia. Lancet 1996;348: 913-916.
  • Alfirevic Z, Roberts D, Martlew V. How strong is the as- sociation between maternal thrombophilia and adverse pregnancy outcome? A systematic review. Eur J Obstet Gynecol Reprod Biol 2002;101:6-14.
  • Many A, Elad R, Yaron Y, et al. Third trimester unex- plained intrauterine fetal death is associated with inher- ited thrombophilia. Obstet Gynecol 2002;99:684-687.
  • Rey E, Kahn SR, David M, et al. Thrombophilic disorders and fetal loss: a metaanalysis. Lancet 2003;361:901- 908.
  • Gonen R, Lavi N, Attias D, et al. Absence of associa- tion of inherited thrombophilia with unexplained third trimester intrauterine fetal death. Am J Obstet Gynecol 2005;192: 742-746.

Komplikasyonlu gebeliklerde trombofili

Year 2013, , 497 - 502, 01.12.2013
https://doi.org/10.5799/ahinjs.01.2013.04.0332

Abstract

Amaç: Gebelik komplikasyonlarında trombofilik faktörlerin görülme sıklığını ve etiyolojideki yerinin araştırılması. Yöntemler: Komplikasyonlu gebeliği olan 54 hasta ve sağlıklı 40 gebe olgu çalışma kapsamına dahil edildi. Faktör V Leiden (FVL) mutasyonu, protein S, protein C, anti-trombin eksiklikleri araştırıldı. Bulgular: Komplike gebeliği olan 54 hastanın 29\'unda preeklampsi, 18\'inde intrauterin büyüme geriliği ve 7 olguda ise intrauterin fetal kayıp saptandı. En sık gözlenen bozukluk FVL mutasyonu idi. FVL mutasyonu hasta ve kontrol gruplarında sırasıyla %27,2 ve %10 olup istatistiksel olarak anlamlı idi. Protein S, protein C, anti-trombin eksiklikleri hasta grubunda kontrol grubuna göre daha yüksek oranda gözlense de anlamlılık saptanmadı (p>0,05). Sonuç: FVL mutasyonu hasta grubunda kontrol grubuna göre yüksek bulundu. Protein C ve anti-trombin eksiklikleri diğer gebelik komplikasyonlarından ziyade preeklampsi ile ilişkili bulunmuştur. Klinisyenler başta preeklampsi olmak üzere komplike gebeliklerde trombofiliyi göz önünde bulundurmalıdırlar.

References

  • De Sefano V, Finazzi G, Mannucci PM. Inherited throm- bophilia: Patogenesis, Clinical syndromes and man- agement. Blood 1996;87:3531-3444.
  • Girling J, de Swiet M. Inherited thrombofilia and pregnan- cy. Curr Opin Obstet Gynecol 1998;10:135-144.
  • Griffin J, Evatt B, Zimmerman T, et al. Deficiency of pro- tein C in congenital thrombotic disease. J Clin Invest 1981;68:1370-1373.
  • Dahlback B, Carlsson M, Svensson PJ. Familial throm- bophilia due to a previously unrecognised mechanism characterized by poor anticoagulant response to activat- ed Protein C: Prediction of a cofactor to activated Protein C. Proc Natl Acad Sci USA 1993; 90:1004-1008.
  • Price DT, Ridker PM. Factor V Leiden mutation and the risks for thromboembolic diseases: a clinical perspec- tive. Ann Intern Med 1997;127:895-903.
  • Griffin JH, Evatt B, Wideman C, et al. Anticoagulant pro- tein C pathway defective in majority thrombophilic pa- tients. Blood 1993;82:1989-1993.
  • Higgins JR, Walshe JJ, Darling MR, Norris L, Bonnar J. Hemostasis in the uteroplacental and peripheral circu- lations in normotensive and pre-eclamptic pregnancies. Am J Obstet Gynecol 1998;179:520-526.
  • McLintock C, Horth RA, Dekker G. Inherited trrombo- philias: Implications for pregnancy associated venous thromboembolism nd obstetric complications. Curr Probl Obstet Gynecol Fertil 2001;24:109-152.
  • Mousa HA, Alfirec Z. Do placental lesions reflect thrombo- philia state in women with adverse pregnancy outcome? Hum Reprod 2000;15:1830-1833.
  • De Stefano V, Chiusolo P, Paciaroni K, et al. Epidemi- ology of factor V Leiden: clinical implications. Semin Thromb Hemost 1998;24:367-379.
  • Deren Ö, Baykal C, Al A, et al. Nedeni açıklanamayan gebelik komplikasyonlarında trombofilik hastalıkların rolü. Jinekoloji ve Obstetrik Bülteni 2000;9:18-22.
  • Özbek U, Tangün Y. Frequency of factor V Leiden (Arg- 506Gln) in Turkey. Br J Haematol 1997;97:504-505.
  • Yokuş O, Balçık ÖŞ, Albayrak M, et al. Thrombophilic risk factors in women with recurrent abortion. J Clin Exp Invest 2010;1:168-172.
  • Dizon-Townson DS, Nelson LM, Easton K, et al. The fac- tor V Leiden mutation may predispose women to severe preeclampsia. Am J Obstet Gynecol 1996 ;175:902-905.
  • Nagy B, Toth T, Rigo J Jr, et al. Detection of factor V leiden mutation in severe pre-eclamptic Hungarian Women. Clin Genet 1998;53:478-481.
  • Lin J, August P. Genetic thrombophilias and preeclamp- sia: a meta-analysis. Obstet Gynecol 2005;105:182-192.
  • Dudding TE, Attia J. The association between adverse pregnancy outcomes and maternal factor V Leiden gen- otype: a meta-analysis. Thromb Haemost 2004;91:700- 711.
  • Livingston JC, Barton JR, Park V, et al. Maternal and fetal inherited thrombophilias are not related to the de- velopment of severe preeclampsia. Am J obstet Gynecol 2001;185:153-157.
  • Paternoster DM, Stella A, Simioni P, et al. Activated pro- tein C resistance in normal and pre-eclamptic pregnan- cies. Gynecol Obstet Invest 2002;54:145-149.
  • Osmanagaoglu MA, Topcuoglu K, Ozeren M, et al. Co- agulation inhibitors in preeclamptic pregnant women. Arch Gynecol Obstet 2005;271:227-230.
  • 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;123:183-187
  • Faught W, Garner PJ, Jones G, et al. Changes in protein C protein S levels in normal pregnancy. Am J Obstet Gy- necol 1995;172:147-150.
  • Dekker GA, de Vries JI, Doelitzsch PM, et al. Underlying disorders associated with severe early-onset preeclam- sia. Am J Obstet Gynecol 1995;173:1042-1048.
  • Kupferminc MJ, Fait G, Many A, et al. Severe pre- eclampsia and high frequency of genetic thrombophilic mutations. Obstet Gynecol 2000;96:45-49.
  • Finazzi G, Caccia R, Barbui T. Different prevalence of thromboembolism in the subtypes of congenital anti- thrombin 3 deficiency: Review of 404 cases. Thromb Haemost 1987;58:1094-1099.
  • Gebhard GS, Hall DR. Inherited and acquired throm- bophilias and poor pregnancy outcome: should we be treating with heparin? Curr Opin Obstet Gynecol 2003;15:501-506.
  • Mc Cowan LM, Craigie S, Taylor RS, et al. Inherited Thrombophilias are not increased in ‘idiopathic’ small for gestational age pregnancies. Am J Obstet Gynechol 2003;188:81-985.
  • Howley HE, Walker M, Rodger MA. A systematic review of the association between factor V Leiden or prothrom- bin gene variant and intrauterine growth restriction. Am J Obstet Gynecol. 2005;192:694-708.
  • Kupferminc M, Eldor A, Steinman N, et al. Increase fre- quency of genetic thrombophilia in women with compli- cations of pregnancy. N Engl J Med 1999;340:9-13.
  • de Vries JIP, Dekker GA, Huijgens PC, et al. Hyperho- mocysteinaemia and protein S deficiency in complicated pregnancies. Br J Obstet Gynaecol 1997;104:1248- 1254.
  • Alonso A, Soto I, Urgelles MF, et al. Acquired and in- herited thrombophilia in women with unexplained fetal losses. Am J Obstet Gynecol 2002;187:1337-1342.
  • Sarig G, Younis JS, 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.
  • Preston FE, Rosendaal FR, Walker ID, et al. Increased fetal loss in women with heritable thrombophilia. Lancet 1996;348: 913-916.
  • Alfirevic Z, Roberts D, Martlew V. How strong is the as- sociation between maternal thrombophilia and adverse pregnancy outcome? A systematic review. Eur J Obstet Gynecol Reprod Biol 2002;101:6-14.
  • Many A, Elad R, Yaron Y, et al. Third trimester unex- plained intrauterine fetal death is associated with inher- ited thrombophilia. Obstet Gynecol 2002;99:684-687.
  • Rey E, Kahn SR, David M, et al. Thrombophilic disorders and fetal loss: a metaanalysis. Lancet 2003;361:901- 908.
  • Gonen R, Lavi N, Attias D, et al. Absence of associa- tion of inherited thrombophilia with unexplained third trimester intrauterine fetal death. Am J Obstet Gynecol 2005;192: 742-746.
There are 37 citations in total.

Details

Primary Language Turkish
Journal Section Research Article
Authors

Ayşe Şahin This is me

Mahmut Nedim Çiçek This is me

Publication Date December 1, 2013
Published in Issue Year 2013

Cite

APA Şahin, A., & Çiçek, M. N. (2013). Komplikasyonlu gebeliklerde trombofili. Journal of Clinical and Experimental Investigations, 4(4), 497-502. https://doi.org/10.5799/ahinjs.01.2013.04.0332
AMA Şahin A, Çiçek MN. Komplikasyonlu gebeliklerde trombofili. J Clin Exp Invest. December 2013;4(4):497-502. doi:10.5799/ahinjs.01.2013.04.0332
Chicago Şahin, Ayşe, and Mahmut Nedim Çiçek. “Komplikasyonlu Gebeliklerde Trombofili”. Journal of Clinical and Experimental Investigations 4, no. 4 (December 2013): 497-502. https://doi.org/10.5799/ahinjs.01.2013.04.0332.
EndNote Şahin A, Çiçek MN (December 1, 2013) Komplikasyonlu gebeliklerde trombofili. Journal of Clinical and Experimental Investigations 4 4 497–502.
IEEE A. Şahin and M. N. Çiçek, “Komplikasyonlu gebeliklerde trombofili”, J Clin Exp Invest, vol. 4, no. 4, pp. 497–502, 2013, doi: 10.5799/ahinjs.01.2013.04.0332.
ISNAD Şahin, Ayşe - Çiçek, Mahmut Nedim. “Komplikasyonlu Gebeliklerde Trombofili”. Journal of Clinical and Experimental Investigations 4/4 (December 2013), 497-502. https://doi.org/10.5799/ahinjs.01.2013.04.0332.
JAMA Şahin A, Çiçek MN. Komplikasyonlu gebeliklerde trombofili. J Clin Exp Invest. 2013;4:497–502.
MLA Şahin, Ayşe and Mahmut Nedim Çiçek. “Komplikasyonlu Gebeliklerde Trombofili”. Journal of Clinical and Experimental Investigations, vol. 4, no. 4, 2013, pp. 497-02, doi:10.5799/ahinjs.01.2013.04.0332.
Vancouver Şahin A, Çiçek MN. Komplikasyonlu gebeliklerde trombofili. J Clin Exp Invest. 2013;4(4):497-502.