Family history of VTE is not grounds for screening for factor V Leiden mutation in pregnancy

Pregnant women with family history as their sole risk factor for venous thromboembolism (VTE) should not be screened for the factor V Leiden mutation, given its low sensitivity and positive predictive values, advised the authors of a recently published study.

Screening for factor V Leiden in pregnant women with either a personal or family history of VTE had been proposed by some in an effort to identify those women at risk for pregnancy-related VTE, which is a common cause of VTE death. Thrombophilia is 1 risk factor for VTE in pregnancy, and the Leiden mutation is the most common inherited thrombophilia.

To assess the correlation between family history of VTE and factor V Leiden mutation carriage in pregnant women without a personal history of VTE, the investigators examined the DNA from 5,168 women with a singleton pregnancy, of which 412 women reported either a first- or second-degree relative, or both, with a thromboembolic event (positive family history).

The positive predictive value of screening for factor V Leiden carrier status in women with a positive family history of VTE was about 5%, and this value did not change regardless of whether the analysis was conducted in women who reported a first-degree relative with VTE or either a first- or second-degree relative with VTE. The sensitivity of the test was not higher than 16.4% in either situation.

The authors concluded that "a positive family history does not appear to be a reliable screening method for factor V Leiden." They further advised that, given the high specificity (92.3% in this study), women with a negative family history for VTE can be reassured that it is unlikely that they are carriers of the factor V Leiden mutation.

Those at increased risk of VTE during pregnancy include women with a personal history of blood clots, those who are obese, and those who are immobile (on bed rest), according to lead investigator Amanda L Horton, MD, from NorthShore University Health System in Evanston, Illinois. Women with a known underlying thrombophilia are at especially high risk of VTE during pregnancy.

In an interview with Contemporary OB/GYN, Horton indicated that screening candidates for the factor V Leiden mutation would include women with a family member with a known factor V Leiden mutation when the woman had not been tested previously for the mutation. "I would also screen if the patient had a personal history of a blood clot and had not undergone thrombophilia testing," she wrote. "Additionally, if a women had multiple first-degree relatives with blood clots, I would also consider screening for factor V Leiden."

In women without other risk factors for VTE, carrying the factor V Leiden mutation does not appear to significantly increase the risk of VTE, according to Horton. She also called for studies to determine the best method to define a positive family history (of VTE) in order to obtain a better estimate of risk.

Horton AL, Momirova V, Dizon-Townson D, et al. Family history of venous thromboembolism and identifying factor V Leiden carriers during pregnancy. Obstet Gynecol. 2010;115(3):521-525.