Genetic susceptibility to pregnancy-related venous thromboembolism: Roles of factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations,☆☆,,★★

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Abstract

Objective: This study’s objective was to evaluate the association between venous thromboembolism during pregnancy and the postpartum period and the factor V Arg 506 Gln (factor V Leiden), the prothrombin G20210A, and methylenetetrahydrofolate reductase C677T polymorphisms. Study Design: In this case-control study 42 case patients and 213 control subjects (parous age-matched women without history of thrombosis) were genotyped for all the polymorphisms. Moreover, antiphospholipid antibodies and protein C, protein S, and antithrombin III deficiencies were investigated in each case. Results: Ten case patients (23.8%) and 4 control subjects (1.9%; odds ratio 16.3, 95% confidence interval 4.8-54.9) carried the factor V Leiden mutation; 13 case patients (31.0%) and 9 control subjects (4.2%; odds ratio 10.2, 95% confidence interval 4.0-25.9) were carriers of the prothrombin G20210A allele. Finally, 12 case patients (28.6%) and 34 control subjects (16.0%; odds ratio 2.1, 95% confidence interval 1.0-4.5) were homozygotes for methylenetetrahydrofolate reductase C677T. Overall, mutations were found in 25 case patients (59.5%) and 47 control patients (22.2%; odds ratio 5.2, 95% confidence interval 4.9-19.6). One patient carried the antithrombin III deficiency and 1 the protein S deficiency, whereas 2 women had a primary antiphospholipid syndrome. Conclusions: The significant risk estimates of having a pregnancy-related venous thromboembolism in the presence of the prothrombotic genetic risk factors analyzed suggest to screen for these mutations women with a personal history of thromboembolic events during pregnancy or the postpartum period. (Am J Obstet Gynecol 1998;179:1324-8.)

Section snippets

Subjects

We performed a case-control study in 2 thrombosis centers at Hospital “Casa Sollievo della Sofferenza,” S. Giovanni Rotondo, and at A. Cardarelli Hospital, Naples. Between January 1995 and March 1998 we observed 42 women with a previous deep venous thrombosis during pregnancy or in the postpartum period. A group of 213 parous women without venous or arterial thromboses served as a control group. Both case patients and control subjects were white women living in Southern Italy. The 2 groups were

Results

As shown in Table I, all deep venous thromboses and pulmonary embolisms were observed in the postpartum period, except for 9 that occurred during pregnancy. Among these postpartum events, 9 (27.3%) occurred after a cesarean delivery. One patient carried antithrombin III deficiency and 1 carried protein S deficiency; in 2 other cases a primary antiphospholipid syndrome was present (Table I). No case patient had arterial or venous thrombosis outside the pregnancy or the postpartum period. Mean

Comment

It has previously been reported that pregnancy and the postpartum period are associated with greatly increased risk for venous thromboembolism among women with an inherited deficiency of a naturally occurring anticoagulant.4 The prevalences of pregnancy-related deep venous thrombosis and pulmonary embolism in a low-risk obstetric population were 0.71 and 0.15 per 1000 deliveries, respectively.21 Several studies have been published on the occurrence of thrombosis during pregnancy and in the

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    From Unità di Aterosclerosi e Trombosi, Casa Sollievo della Sofferenza, S. Giovanni Rotondo, Divisione di Ematologia, Unità di Coagulazione, Ospedale A. Cardarelli, and Istituto di Medicina Interna e Geriatria, Università di Palermo.

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    Supported by Telethon-Italy (grant E C 561).

    Reprint requests: Elvira Grandone, MD, Unità di Aterosclerosi e Trombosi, IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini, S. Giovanni Rotondo (FG), 71013 Italy.

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