Journal of Hematology & Thromboembolic Diseases
Open Access

Pregnancy Complications and Management of Factor V Leiden Thrombophilia

Davood Shafie^{* *}Correspondence: Davood Shafie, Department of Oncology, Keele University Medical School, Cheltenham, United Kingdom, Email:

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Description

A poor anticoagulant response to activated Protein C and an elevated risk for venous thromboembolism are two features of the genetic disease factor V Leiden. The most frequent symptoms are deep vein thrombosis and pulmonary embolism; however thrombosis can also occur in unexpected places [1]. According to the available data, the mutation may only have a minor impact on the likelihood of recurrent venous thromboembolism following initial treatment. Despite the high likelihood of a healthy pregnancy, factor V Leiden is also linked to a 2to3 fold greater relative risk for miscarriage and perhaps other obstetric problems. The number of Factor V Leiden alleles, co-occurring hereditary and acquired thrombophilic diseases, and external risk factors all affect how Factor V Leiden manifests clinically [2]. A DNA examination of the F5 gene, which codes for the Factor V protein, or the activated Protein C resistance assay (a coagulation screening test) are both necessary for diagnosis. Standard treatment recommendations are followed for the first acute thrombosis. Individual assessments of the risks for recurrent venous thromboembolism and anticoagulantrelated bleeding are used to determine the best duration of anticoagulation [3,4]. Long-term anticoagulation is not typically advised for asymptomatic Factor V Leiden heterozygotes in the absence of a history of thrombosis, while prophylactic anticoagulation may be taken into account in high-risk clinical situations. The choice to test at-risk family members should be taken individually if there is no proof that early detection lowers morbidity or mortality [5].

Pregnancy complications

The relative risk of miscarriage and other issues such preeclampsia, intrauterine growth restriction, and placental abruption is two to three times higher in those with Factor V Leiden. A Factor V Leiden mutation, however, is only one of many predisposing factors that contribute to these negative consequences. Factor V Leiden is likely only one of many genetic and environmental factors that contribute to pregnancy problems. Overall, even in homozygous women, the likelihood of a healthy pregnancy outcome is high [5-8].

Women with unexplained recurrent pregnancy loss had a significant prevalence of Factor V Leiden heterozygosity (up to 30%), which suggests a 2 to 5 fold increase in risk. In a prospective research, women who were Factor V Leiden heterozygotes and had a history of recurrent early miscarriage had a lower live birth rate (38%) than those who had a similar history of failed pregnancies but did not have the mutation (69%) [9]. A second pregnancy following a first foetal loss would not be affected by the gene, according to other research that revealed no relationship between pregnancy loss and the mutation. Strong associations with foetal loss were discovered by several meta-analyses. According to some data, women with Factor V Leiden are more likely to experience pregnancy losses in the second or third trimester than in the first [10]. According to a meta-analysis, a heterozygous mutation raised the chance of late unexplained foetal loss by twofold and the risk of loss in the second trimester by fourfold when compared to the first trimester. A 4-fold increased risk of unexplained stillbirth and an 11-fold greater risk of stillbirth connected to placental infarction were both linked to factor V Leiden heterozygosity [11-13]. According to a recent study, heterozygous women had a 5-fold higher risk of a late foetal loss (after 12 weeks of gestation) than homozygous women did, and those lacking the mutation had an 11-fold higher risk [14]. The frequency of early (first trimester) pregnancy losses, however, varied little among the three groups, showing that the mutation is more strongly associated with late pregnancy loss. One theory is that, in contrast to first-trimester losses, which are more frequently attributed to other causes, late pregnancy losses are due to thrombosis of the placental veins [14,15]. Some data, however, point to a possible link between Factor V Leiden and an elevated risk of first-trimester loss.

Conclusion

An approximate 7-fold greater chance of getting a DVT during pregnancy is associated with factor V Leiden. If a woman with factor V Leiden intends to become pregnant, she should talk to her obstetrician and/or hematologist about her options. Most factor V Leiden patients have healthy pregnancies and just need attentive monitoring during pregnancy. Treatment with an anticoagulant during a future pregnancy can stop recurrence issues for people with a history of DVT or PE.

References

1. Folsom AR, Cushman M, Tsai MY, Aleksic N, Heckbert SR, Boland LL, et al. A prospective study of venous thromboembolism in relation to factor V Leiden and related factors. Blood. 2002;99(8):2720-2725.

   [Crossref] [Google Scholar] [PubMed]

2. Goldhaber SZ, Bounameaux H. Pulmonary embolism and deep vein thrombosis. Lancet. 2012;379(9828):1835-1846.

   [Crossref] [Google Scholar]

3. Rosendaal FR, Vessey M, Rumley A, Daly E, Woodward M, Helmerhorst FM, et al. Hormonal replacement therapy, prothrombotic mutations and the risk of venous thrombosis. Br J Haematol. 2002;116(4):851-854.

   [Crossref] [Google Scholar] [PubMed]

4. Tsai AW, Cushman M, Rosamond WD, Heckbert SR, Polak JF, Folsom AR. Cardiovascular risk factors and venous thromboembolism incidence: The longitudinal investigation of thromboembolism etiology. Arch Intern Med. 2002;162(10):1182-1189.

   [Crossref] [Google Scholar] [PubMed]

5. Nichols WC, Amano K, Cacheris PM, Figueiredo MS, Michaelides K, Schwaab R, et al. Moderation of hemophilia A phenotype by the factor V R506Q mutation. Blood. 1996; 88 (4): 1183-1187.

   [Crossref] [Google Scholar] [PubMed]

6. Lee DH, Walker IR, Teitel J, Poon MC, Ritchie B, Akabutu J, et al. Effect of the factor V Leiden mutation on the clinical expression of severe hemophilia A. Thromb Haemost. 2000;83(03):387-391.

   [Crossref] [Google Scholar] [PubMed]

7. Kapiotis S, Quehenberger P, Jilma B, Handler S, Pabinger-Fasching I, Mannhalter C, et al. Improved characteristics of aPC-resistance assay: Coatest aPC resistance by predilution of samples with factor V deficient plasma. Am J Clin Pathol. 1996;106(5):588-593.

   [Crossref] [Google Scholar] [PubMed]

8. Takamiya O, Ishida F, Kodaira H, Kitano K. APC-resistance and Mnl I genotype (Gin 506) of coagulation factor V are rare in Japanese population. Thromb Haemost. 1995;74(09):996.

   [Crossref] [Google Scholar] [PubMed]

9. Irani‐Hakime N, Tamim H, Kreidy R, Almawi WY. The prevalence of factor V R506Q mutation‐Leiden among apparently healthy Lebanese. Blood. 2000;65(1):45-49.

   [Crossref] [Google Scholar] [PubMed]

10. Awidi A, Shannak M, Bseiso A, Kailani MA, Kailani MA, Omar N, et al. High prevalence of factor V Leiden in healthy Jordanian Arabs. Thromb Haemost. 1999 Apr;81(04):582-584.

    [Crossref] [Google Scholar] [PubMed]

11. Castoldi E, Rosing J. APC resistance: Biological basis and acquired influences. J Thromb Haemost. 2010;8(3):445-453.

    [Crossref] [Google Scholar] [PubMed]

12. Koster T, Vandenbroucke JP, Rosendaal FR, De Ronde H, Briët E, Bertina RM. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. Lancet. 1993;342(8886-8887):1503-1506.

    [Crossref] [Google Scholar] [PubMed]

13. Heijmans BT, Westendorp RG, Knook DL, Kluft C, Slagboom EP. The risk of mortality and the factor V Leiden mutation in a population-based cohort. Thromb Haemost. 1998;80(10):607-609.

    [Crossref] [Google Scholar] [PubMed]

14. Ridker PM, Miletich JP, Stampfer MJ, Goldhaber SZ, Lindpaintner K, Hennekens CH. Factor V Leiden and risks of recurrent idiopathic venous thromboembolism. Circulation. 1995;92(10):2800-28002.

    [Crossref] [Google Scholar] [PubMed]

15. Milio G, Siragusa S, Minà C, Amato C, Corrado E, Grimaudo S, et al. Superficial venous thrombosis: Prevalence of common genetic risk factors and their role on spreading to deep veins. Thromb Res. 2008;123(2):194-199.

    [Crossref] [Google Scholar] [PubMed]