Does asymptomatic carriage of FV Leiden and FII prothrombin mutations in heterozygous configuration pose an increased risk of thrombembolic complications in the course of pregnancy, labor and puerperium?

Blanka Vavrinkova,Peter Salaj,Ivana Hadacova,Martin Hruda,Ingrid Hrachovinova,Tomas Binder

doi:10.5507/bp.2012.070

Abstract

To evaluate the course of pregnancy and puerperium in asymptomatic carriers of FV Leiden and FII prothrombin mutation in heterozygous configuration in terms of risk of thrombembolic disease (TED) and late pregnancy complications. To evaluate whether global prophylactic LMWH administration during pregnancy benefits these women. We monitored the incidence of thrombembolic events and severe late pregnancy complications in 473 asymptomatic carriers of FV Leiden and FII prothrombin mutation in heterozygous configuration. In 253 women, preventive LMWH application was introduced already during pregnancy. In 220 women, the application of LMWH was commenced as late as on the delivery day. In both groups application of LMWH continued during the puerperium. The incidence of TED in the whole group of carriers of thrombophylic mutations accounted for 0.19%. The incidence of severe late pregnancy complications was low - 2.5% compared with general population of pregnant women (6.4%). No direct causal relationship was established between asymptomatic carriage of Leiden and prothrombin mutation in heterozygous configuration and the occurrence of severe late pregnancy complications. There was no benefit from general LMWH prophylaxis started as early as pregnancy in these women and thus we consider it unnecessary.

Highlights

Pregnancy of carriers of thrombophylic mutations (TM) is considered by many authors to be associated with a high risk in terms of development of both thrombembolic disease and severe late pregnancy complications
Factor V Leiden mutation is rare in Asian and African populations and is higher in European population, with the highest frequency reported in the Eastern Mediterranean region. 20210 position of the protrombin gene enhances the function of prothrombin and results in an increased risk of thrombosis
We recorded 2 cases of severe IUGR (0.79%), l case of placenta abruption (0.39%), 2 cases of developed HELLP syndrome (0.79%), 2 cases of a more severe form of preeclampsia (0.79%) and one case of stillbirth (0.39%)

Summary

Introduction

Pregnancy of carriers of thrombophylic mutations (TM) is considered by many authors to be associated with a high risk in terms of development of both thrombembolic disease and severe late pregnancy complications. The factor V Leiden mutation results from a substitution of adenine for the normal guanine at the 1691 position of the factor V gene. Factor V Leiden mutation is rare in Asian and African populations and is higher in European population, with the highest frequency reported in the Eastern Mediterranean region. 20210 position of the protrombin gene enhances the function of prothrombin (factor II) and results in an increased risk of thrombosis. The prothrombin heterozygote mutation occurs in approximately 2% of the general population but appears to be less common in African Americans. The genes for factor V Leiden and prothrombin follow an autosomal dominant pattern of inheritance because the heterozygote is considered an increased risk for thrombosis

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