The extent of Factor V Leiden thrombophilia in maternal and fetal health. Risk of placenta-mediated pregnancy complications - a systematic review

Autori

  • Simina-Andreea BARBU Carol Davila University of Medicine and Pharmacy, Bucharest
  • Livia-Gabriela BĂLĂNOIU Carol Davila University of Medicine and Pharmacy, Bucharest
  • Radu-Marian FLOREA Carol Davila University of Medicine and Pharmacy, Bucharest
  • Cetin MAMBET Carol Davila University of Medicine and Pharmacy, Bucharest

DOI:

https://doi.org/10.5281/zenodo.8014943

Cuvinte cheie:

Factor V Leiden, hereditary thrombophilia, recurrent pregnancy loss, preeclampsia, intrauterine growth restriction, obstetrical complications, systematic review

Rezumat

Factor V Leiden represents a mutation in the gene coding the production of V factor, being the most common cause for hereditary thrombophilia, affecting up to 50% of the patients with familial thrombophilia. Pregnant women are generally considered a population at risk for developing different associated pathologies potentially leading to premature parturition, or other complications. Existing literature seems to point towards a significant connection between the Factor V Leiden thrombophilia and potential complications, including thromboembolic events, preeclampsia, recurrent pregnancy loss and intrauterine growth restrictions.

Articles published in the past 9 years were sourced on PubMed, using keywords such as "factor V Leiden", "FVL", "pregnancy". We included systematic reviews, meta-analyses, case-control and retrospective studies. Placenta-mediated pregnancy complications (PMPC), such as recurrent pregnancy loss (RPL), preeclampsia (PE), and intrauterine growth restriction (IUGR) represented the inclusion criteria. Associated pathologies, comparative studies, screening, women with history of IVF and embryo transfer, clinical trials, paternal and fetal mutations were excluded. Bias risk was not assessed, and an abstraction method was used for data synthesis.

 

21 randomized control trials were selected. Obstetrical outcomes such as RPL, PE, and IUGR were analyzed in connection with the presence of FVL. Bias risk was not assessed. FVL was associated with a higher risk of RPL in Padda J et. al (2021), Hamedi et al. (2020), Jusić A et al. (2018), and Pietropolli A et al. (2014), with a prevalence of 12.6% (OR=2.4), 12.6% (OR=2.37), 7.5% (p=0.021), and 10% (p=0.05). A connection between FVL and preeclampsia was found in Ahmed NA et al. (2019) - 9.6% (OR=18.60), fortified by Li Y et al. (2019) and Fong FM et. al. (2014). FVL had a prevalence of 40% in patients with IUGR in Padda J et al. (2021), while Coriu L et al. (2014) showed similar results, but without statistical significance (OR=1.58, p>0.05).

FVL is associated with higher risk of RPL, preeclampsia and IUGR. However, due to the multifactorial aspects of obstetrical complications, stronger research is recommended for a better understanding in the future.

Biografii autori

Simina-Andreea BARBU, Carol Davila University of Medicine and Pharmacy, Bucharest

Student 4th year, Carol Davila University of Medicine and Pharmacy - Bucharest, Romania

Livia-Gabriela BĂLĂNOIU, Carol Davila University of Medicine and Pharmacy, Bucharest

Student 4th year, Carol Davila University of Medicine and Pharmacy - Bucharest, Romania

Radu-Marian FLOREA, Carol Davila University of Medicine and Pharmacy, Bucharest

Student 5th year, Carol Davila University of Medicine and Pharmacy - Bucharest, Romania

Cetin MAMBET, Carol Davila University of Medicine and Pharmacy, Bucharest

Student 3rd year, Carol Davila University of Medicine and Pharmacy - Bucharest, Romania

Referințe

Van Cott EM, Khor B, Zehnder JL. Factor VLeiden: Factor V Leiden. Am J Hematol. 2016 Jan;91(1):46–9.

Koster T, Vandenbroucke J, Rosendaal F, de Ronde H, Briët E, Bertina R. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. The Lancet. 1993 Dec;342(8886–8887):1503–6.

Corral J, Roldan V, Vicente V. Deep venous thrombosis or pulmonary embolism and factor V Leiden: enigma or paradox. Haematologica. 2010 Jun 1;95(6):863–6.

Magley M, Hinson MR. Eclampsia. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 [cited 2023 Jan 29]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK554392/

Spina V. The impact of the Factor V Leiden mutation on pregnancy. Human Reproduction Update. 2000 May 1;6(3):301–6.

Carroll R, Rebarber A, Booker W, Fox N, Saltzman D, Lam-Rachlin J, et al. Double versus single thrombophilias during pregnancy. The Journal of Maternal-Fetal & Neonatal Medicine. 2018 Oct 2;31(19):2590–3.

Liu X, Chen Y, Ye C, Xing D, Wu R, Li F, et al. Hereditary thrombophilia and recurrent pregnancy loss: a systematic review and meta-analysis. Hum Reprod. 2021 Apr 20;36(5):1213–29.

Reddy RRN, Mutreja D, Moorchung N, Mukhopadhyay I. Recurrent pregnancy loss: can factor V Leiden mutations be a cause. Obstet Gynecol Sci. 2019;62(3):179.

Elzein HO, Saad AA, Yousif AA, Elamin E, Abdalhabib EK, Elzaki SEG. Evaluation of Factor V Leiden and prothrombin G20210A mutations in Sudanese women with severe preeclampsia. Current Research in Translational Medicine. 2020 Apr;68(2):77–80.

Kashif S, Kashif MA, Saeed A. The association of factor V leiden mutation with recurrent pregnancy loss. J Pak Med Assoc. 2015 Nov;65(11):1169–72.

Padda J, Khalid K, Mohan A, Pokhriyal S, Batra N, Hitawala G, et al. Factor V Leiden G1691A and Prothrombin Gene G20210A Mutations on Pregnancy Outcome. Cureus [Internet]. 2021 Aug 15 [cited 2023 Jan 29]; Available from: https://www.cureus.com/articles/67636-factor-v-leiden-g1691a-and-prothrombin-gene-g20210a-mutations-on-pregnancy-outcome

Ahmed NA, Adam I, Elzaki SEG, Awooda HA, Hamdan HZ. Factor-V Leiden G1691A and prothrombin G20210A polymorphisms in Sudanese women with preeclampsia, a case -control study. BMC Med Genet. 2019 Dec;20(1):2.

Hamedi B, Feulefack J, Khan A, Sergi C. Association between factor V Leiden mutation and recurrent pregnancy loss in the middle east countries: a Newcastle–Ottawa meta-analysis. Arch Gynecol Obstet. 2020 Aug;302(2):345–54.

Jusić A, Balić D, Avdić A, Pođanin M, Balić A. The association of factor V G1961A (factor V Leiden), prothrombin G20210A, MTHFR C677T and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss in Bosnian women. Medicinski Glasnik [Internet]. 2018 [cited 2023 Jan 29];(2). Available from: https://doi.org/10.17392/948-18

Pietropolli A, Giuliani E, Bruno V, Patrizi L, Piccione E, Ticconi C. Plasminogen activator inhibitor-1, factor V, factor II and methylenetetrahydrofolate reductase polymorphisms in women with recurrent miscarriage. Journal of Obstetrics and Gynaecology. 2014 Apr;34(3):229–34.

Coriu L, Copaciu E, Tulbure D, Talmaci R, Secara D, Coriu D, et al. Inherited thrombophilia in pregnant women with intrauterine growth restriction. Maedica (Bucur). 2014 Dec;9(4):351–5.

Gils C, Nybo M. Thrombophilia prevalence among women with placenta-mediated pregnancy complications. International Journal of Gynecology & Obstetrics. 2016 Aug;134(2):156–9.

Eslami MM, khalili M, Soufizomorrod M, Abroun S, Razi B. Factor V Leiden 1691G > A mutation and the risk of recurrent pregnancy loss (RPL): systematic review and meta-analysis. Thrombosis J. 2020 Dec;18(1):11.

Sergi C, Al Jishi T, Walker M. Factor V Leiden mutation in women with early recurrent pregnancy loss: a meta-analysis and systematic review of the causal association. Arch Gynecol Obstet. 2015 Mar;291(3):671–9.

Li Y, Ruan Y. Association of hypertensive disorders of pregnancy risk and factor V Leiden mutation: A meta‐analysis. J Obstet Gynaecol Res. 2019 Jul;45(7):1303–10.

Fong FM, Sahemey MK, Hamedi G, Eyitayo R, Yates D, Kuan V, et al. Maternal Genotype and Severe Preeclampsia: A HuGE Review. American Journal of Epidemiology. 2014 Aug 15;180(4):335–45.

Brenner B, Sarig G, Weiner Z, Younis J, Blumenfeld Z, Lanir N. Thrombophilic Polymorphisms Are Common in Women with Fetal Loss without Apparent Cause. Thromb Haemost. 1999;82(07):6–9.

Raziel A, Friedler S, Schachter M, Ron-El R, Kornberg Y, Sela BA. Hypercoagulable Thrombophilic Defects and Hyperhomocysteinemia in Patients with Recurrent Pregnancy Loss. Am J Reprod Immunol. 2001 Feb;45(2):65–71.

Lenz B, Samardzija M, Drenjancevic D, Zibar D, Samardzija M, Milostic-Srb A. The investigation of hereditary and acquired thrombophilia risk factors in the development of complications in pregnancy in Croatian women. The Journal of Maternal-Fetal & Neonatal Medicine. 2016 Jan 17;29(2):264–9.

Descărcări

Publicat

2023-05-03

Cum cităm

BARBU, S.-A., BĂLĂNOIU, L.-G., FLOREA, R.-M., & MAMBET, C. (2023). The extent of Factor V Leiden thrombophilia in maternal and fetal health. Risk of placenta-mediated pregnancy complications - a systematic review. Hemostasis Thrombosis and Anemic Syndromes, 1(1). https://doi.org/10.5281/zenodo.8014943

Număr

Secțiune

Systematic review

##category.category##