Advertisement

Annals of Hematology

, Volume 86, Issue 10, pp 727–731 | Cite as

Factor V Leiden and G20210A prothrombin mutations in patients with recurrent pregnancy loss: data from the southeast of Turkey

  • Abdullah AltintasEmail author
  • Semir Pasa
  • Nurten Akdeniz
  • Timucin Cil
  • Murat Yurt
  • Orhan Ayyildiz
  • Sabri Batun
  • Hilmi Isi
Original Article

Abstract

Factor V Leiden (FV-Leiden) and prothrombin gene mutations (FII G20210A) are well-established independent risk factors for thrombosis. In the recent years, many studies have suggested that these mutations are associated with an increased risk of recurrent pregnancy loss (RPL). We aimed to investigate the prevalence of these molecular defects in subjects with a history of early RPL. One hundred and fourteen women with three or more consecutive unexplained first-trimester miscarriages were compared to 185 parous women with uncomplicated pregnancies from the same ethnic origin. The presence of FV-Leiden and FII G20210A mutations was assessed by polymerase chain reaction analysis. Overall, 11 out of the 114 women with early RPL (9.6%) had either FV-Leiden or FII G20210A mutation, as compared with 16 out of the 185 women with normal pregnancies (8.6%; p = 0.756). The prevalence of FV-Leiden mutation was 7.9% (9/114) in patient group, compared with 7% (13/185) in control group (p = 0.780). One hundred and two patients were primary and 12 were secondary aborters. All FV-Leiden positive cases were primary aborters (8.8%; 9/102, p = 0.584). Concerning the FII G20210A, two out of 114 (1.7%) were first-trimester RPL (primary aborters) and three out of 185 (1.6%) controls were carriers of the FII G20210A mutation (1.7 vs 1.6%, p = 0.931). The results obtained from patients with first-trimester RPL and the control group have no statistical significant differences in the prevalence of FV-Leiden and FII G20210A mutations. These results suggest that mutations have no role in etiology of first-trimester recurrent abortions.

Keywords

Recurrent pregnancy loss Factor V Leiden FII G20210A 

References

  1. 1.
    Santis MD, Cavaliere AF, Straface G, Gianantonio ED, Caruso A (2006) Inherited and acquired thrombophilia: pregnancy outcome and treatment. Reprod Toxicol 22:227–233PubMedCrossRefGoogle Scholar
  2. 2.
    Regan L, Rai R (2002) Thrombophilia and pregnancy loss. J Reprod Immunol 55:163–180PubMedCrossRefGoogle Scholar
  3. 3.
    Dizon-Townson DS, Kinney S, Branch DW, Ward K (1997) The factor V Leiden mutation is not a common cause of recurrent miscarriage. J Reprod Immunol 34:217–223PubMedCrossRefGoogle Scholar
  4. 4.
    Brenner B, Sarig G, Weiner Z, Younis J, Blumenfeld Z, Lanir L (1999) Thrombophilic polymorphisms are common in women with fetal loss without apparent cause. Thromb Haemost 82:6–9PubMedGoogle Scholar
  5. 5.
    Sarig G, Younis JS, Hoffman R, Lanir R, Blumenfeld Z, Brenner B (2002) Thrombophilia is common in women with idiopathic pregnancy loss and is associated with late pregnancy wastage. Fertil Steril 77:342–347PubMedCrossRefGoogle Scholar
  6. 6.
    Wramsby ML, Sten-Linder M, Bremme K (2000) Primary habitual abortions are associated with high frequency of Factor V Leiden mutation. Fertil Steril 74:987–991PubMedCrossRefGoogle Scholar
  7. 7.
    Ridker PM, Miletich JP, Buring JE, Ariyo AA, Price DT, Manson JE, Hill JA (1998) Factor V Leiden mutation as a risk factor for recurrent pregnancy loss. Ann Intern Med 128:1000–1003PubMedGoogle Scholar
  8. 8.
    Souza SS, Ferriani RA, Pontes AG, Zago MA, Franco RF (1999) Factor V Leiden and factor II G20210A mutations in patients with recurrent abortion. Hum Reprod 14:2448–2450PubMedCrossRefGoogle Scholar
  9. 9.
    Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsman PH (1994) Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 369:64–67PubMedCrossRefGoogle Scholar
  10. 10.
    Poort SR, Rosendaal FR, Reitsma PH, Bertina RM (1996) 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 88:3698–3703PubMedGoogle Scholar
  11. 11.
    Rai R, Shlebak A, Cohen A, Backos M (2001) Factor V Leiden and acquired activated protein C resistance among women with recurrent miscarriage. Hum Reprod 16:961–965PubMedCrossRefGoogle Scholar
  12. 12.
    Pauer HU, Voigt-Tschirschwitz T, Hinney B, Burfeind P, Wolf C, Emons G (2003) Analyzes of three common thrombophilic gene mutations in German women with recurrent abortions. Acta Obstet Gynecol Scand 82:942–947PubMedCrossRefGoogle Scholar
  13. 13.
    Triplett DA, Harris EN (1989) Antiphospholipid antibodies and reproduction. Am J Reprod Immunol 21:123–131PubMedGoogle Scholar
  14. 14.
    Sanson BJ, Friederich PW, Simioni P (1996) The risk of abortion and stillbirth in antithrombin-, protein C-, and protein S-deficient women. Thromb Haemost 75:387–388PubMedGoogle Scholar
  15. 15.
    Dizon-Townson D, Meline L, Nelson L, Narner M, Ward K (1997) Fetal carriers of factor V Leiden mutation are prone to miscarriage and placental infarction. Am J Obstet Gynecol 177:402–405PubMedCrossRefGoogle Scholar
  16. 16.
    Rai R, Regan L, Chitolie A, Donald J, Cohen H (1996) Placental thrombosis and second trimester miscarriage in association with activated protein C resistance. Br J Obstet Gyneacol 103:842–844Google Scholar
  17. 17.
    Deitcher SR, Caiola E, Jaffer A (2000) Demystifying two common genetic predisposition to venous thrombosis. Clevel Clin J Med 67:825–836Google Scholar
  18. 18.
    Kalkanli S, Ayyildiz O, Tiftik N, Batun S, Isikdogan A, Ince H, Tekes S, Muftuoglu E (2006) Factor V Leiden mutation in venous thrombosis in southeast Turkey. Angiology 57(2):193–196PubMedCrossRefGoogle Scholar
  19. 19.
    Gurgey A, Mesci L (1997) The prevalence of factor V Leiden (1691G→A) mutation in Turkey. Turk J Pediatr 39:313–315PubMedGoogle Scholar
  20. 20.
    Rosendaal FR, Doggen CJ, Zivelin A, Arruda VR, Aiach M, Siscovick DS, Hillarp A, Watzke HH, Bernardi F, Cumming AM, Preston FE, Reitsma PH (1998) Geographic distribution of the 20210 G to A prothrombin variant. Thromb Haemost 79:706–708PubMedGoogle Scholar
  21. 21.
    Ayyildiz O, Kalkanli S,Batun S, Aybak M, Isikdogan A, Tiftik N, Bolaman Z, Soker M, Muftuoglu E (2004) Prothrombin G20210A gene mutation with LightCycler polymerase chain reaction in venous thrombosis and healthy population in the southeast of Turkey. Heart Vessels 19:164–166PubMedCrossRefGoogle Scholar
  22. 22.
    Akar N, Misirlioglu M, Akar E, Avci F, Yalcin A (1998) Prothrombin gene 20210 G-A mutations in Turkish population. Am J Hematol 58:249PubMedCrossRefGoogle Scholar
  23. 23.
    Finan RR, Tamim H, Ameen G, Sharida HE, Rashid M, Almawi WY (2002) Prevalence of Factor V G1691A (Factor V-Leiden) and prothrombin G20210A gene mutations in a recurrent miscarriage population. Am J Hematol 71:300–305PubMedCrossRefGoogle Scholar
  24. 24.
    Reznikoff-Etiévant MF, Cayol V, Carbonne B, Robert A, Coulet F, Milliez J (2001) Factor V Leiden and prothrombin mutations are risk factors for very early recurrent miscarriage. Br J Obstet Gyneacol 108:1251–1254CrossRefGoogle Scholar
  25. 25.
    Dudding TE, Attia J (2004) The association between adverse pregnancy outcomes and maternal factor V Leiden genotype: a meta-analysis. Thromb Haemost 91:700–711PubMedGoogle Scholar
  26. 26.
    Rey E, Kahn SR, David M, Shrier I (2003) Thrombophilic disorders and fetal loss: a meta analysis. Lancet 361:901–908PubMedCrossRefGoogle Scholar
  27. 27.
    Kovalevsky G, Gracia CR, Berlin JA, Sammel MD, Barnhart KT (2004) Evaluation of the association between hereditary thrombophilias and recurrent pregnancy loss: a meta-analysis. Arch Intern Med 164:558–563PubMedCrossRefGoogle Scholar
  28. 28.
    Hashimoto K, Shizusawa Y, Shimoya K, Ohashi K, Shimizu T, Azuma C, Murata Y (1999) The factor V Leiden mutation in Japanese couples with recurrent spontaneous abortion. Hum Reprod 14:1872–1874PubMedCrossRefGoogle Scholar
  29. 29.
    Kutteh WH, Park VM, Deitcher SR (1999) Hypercoagulable state mutation analysis in white patients with early-first trimester recurrent pregnancy loss. Fertil Steril 71:1048–1053PubMedCrossRefGoogle Scholar
  30. 30.
    Porter TF, Scott JR (2005) Evidence-based care of recurrent miscarriage. Best Pract Res Clin Obstet Gynaecol 19:85–101PubMedGoogle Scholar
  31. 31.
    Aksoy M, Tek I, Karabulut H, Berker B, Soylemez F (2005) The role of thrombophilia related to Factor V Leiden and Factor II G20210A mutations in recurrent abortions. J Pak Med Assoc 55:104–108PubMedGoogle Scholar
  32. 32.
    Karateke A, Haliloglu B, Gurbuz A (2005) Third trimester nonrecurrent fetal loss is associated with factor V Leiden and prothrombin gene mutations. J Matern Fetal Neonatal Med 18:299–304PubMedCrossRefGoogle Scholar
  33. 33.
    Christiansen OB, Andersen AMN, Bosch E, Daya S, Delves PJ, Hviid TV, Kutteh WH, Laird SM, Lee TC, van der Ven K (2005) Evidence-based investigations and treatments of recurrent pregnancy loss. Fertil Steril 83:821–839PubMedCrossRefGoogle Scholar
  34. 34.
    Carp H, Salomon O, Seidman D, Dardik D, Rosenberg N, Inbal A (2002) Prevalence of genetic markers for thrombophilia in recurrent pregnancy loss. Human Reprod 16:1633–1637CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Abdullah Altintas
    • 1
    Email author
  • Semir Pasa
    • 1
  • Nurten Akdeniz
    • 2
  • Timucin Cil
    • 1
  • Murat Yurt
    • 3
  • Orhan Ayyildiz
    • 1
  • Sabri Batun
    • 3
  • Hilmi Isi
    • 4
  1. 1.Internal Medicine, Department of Hematology–OncologyDicle UniversityDiyarbakirTurkey
  2. 2.Department of Obstetrics and GynecologyDicle UniversityDiyarbakirTurkey
  3. 3.Molecular Genetics and Hematology LaboratoryDicle UniversityDiyarbakirTurkey
  4. 4.Department of Molecular GeneticsDicle UniversityDiyarbakirTurkey

Personalised recommendations