April 17, 2002 Access past issues

Reviewed by: Viola Vaccarino, MD, PhD Emory University

The Health Outcome

Pregnancy and puerperium are known risk factors for venous thromboembolism (VTE) (1, 2).  The incidence of VTE during pregnancy is 1 per 1,000 (1,2) and increases 10 times during the postpartum period (3). These incidence rates are considerably higher than those reported for women of similar age in the general population. A variety of clotting inhibitor deficiencies have been identified as risk factors for VTE in pregnancy, but most of these defects are rare. Factor V Leiden mutation is relatively common: it affects 5% of the southern European population.

The Finding

The purpose of the study by Tormene et al. (4), therefore, was to assess the relation between factor V Leiden mutation and incidence of pregnancy-related VTE using a case-control design. Study subjects were women who were family members of patients who had both factor V Leiden mutation and an objective diagnosis of VTE. All the female relatives who had been pregnant at least once and who were at least 15 years of age were screened for factor V Leiden and for other coagulation defects (antithrombin, proteins S and C, hyperh omocysteinemia, lupus anticoagulant, and prothrombin variant G20210A). Of these women, 105 screened positive for factor V Leiden and comprised the cases; 81 women screened negative and comprised the controls. 

Diagnosis of VTE was assessed retrospectively and had to be documented through clinical tests or through at least 3 months of anticoagulant treatment. VTE events were considered in the analysis only if they occurred during pregnancy or during the postpartum period.  

The frequency of VTE episodes per number of pregnancies were as follows: noncarriers: 1/215 (0.46%, 95% CI 0.01-2.6); heterozygous for factor V Leiden alone: 6/242 (2.48%, 95% CI 0.9-5.4); double heterozygous for factor V Leiden and other coagulation defects: 1/14 (7.1%, 95% CI 0.18-39.8); homozygous for factor V Leiden: 1/14 (7.1%, 95% CI: 0.18-39.8). The authors conclude that factor V Leiden is a risk factor for VTE during pregnancy or puerperium (4,5).

Public Health Implications

The authors suggest that screening for factor V Leiden mutation may be useful for women of fertile age who are relatives of probands with a history of VTE, because those women who screen positive may benefit from thromboprophylaxis during pregnancy and puerperium.  However, these potential public health implications will depend on whether these findings are replicated in unselected populations of pregnant women (i.e., not just women who are members of families who have a history of VTE and factor V Leiden mutation, as in this study). If confirmed to be an important risk factor for pregnancy-related VTE, and if clinical trials document the benefits and the cost-effectiveness of thromboprophylactic treatments during pregnancy in factor-V Leiden carriers, screening for factor V Leiden mutation might become warranted in pregnant women, or at least in those women who have a family history of VTE.

References

1. Anderson BS et al. The cumulative incidence of venous thromboembolism during pregnancy and puerperium: an 11-year Danish population-based study of 63,300 pregnancies. Acta Obstet Gynecol Scand 1998;77:170-3.
2. Lindqvist P et al. Thrombotic risk during pregnancy: a population study. Obstet Gynecol 1999;94:595-9.
3. Ray JC, et al. Deep vein thrombosis during pregnancy and the puerperium: a meta-analysis of the period of risk and the leg of presentation. Obstet Gynecol Surv 1999;54:265-71.
4. Tormene D et al. Factor V Leiden mutation and risk of venous thromboembolism in pregnant women. Haematologica 2001;86:1305-9.
5. E-Journal Club abstraction form on Tormene D et al.