Objectives: The factor V Leiden mutation is the most common genetic predisposition to thrombosis. However, little is known concerning the reproductive outcome of mutation carriers or prenatal expressivity of this thrombogenic mutation. Our purpose was to examine whether this mutation presents phenotypically as miscarriage or idiopathic placental thrombosis.
Study design: We performed two studies. First, a case-control comparison to determine whether fetal or maternal carriers of the factor V Leiden mutation are at risk for spontaneous miscarriage was performed, and, second, a cohort study evaluating placental infarction in fetuses carrying this mutation was performed.
Results: We found a twofold increase in the factor V Leiden carrier frequency in 12 of 139 (8.6%) abortuses compared with 17 of 403 (4.2%) unselected pregnant women seen in the labor and delivery suite and, even more remarkable, a tenfold increase in the fetal carrier frequency in 10 of 24 (42%) placentas with > 10% placental infarction compared with 7 of 372 (1.9%) placentas with < 10% placental infarction.
Conclusions: These findings suggest a prenatal phenotype and effects of this mutation at the fetoplacental interface. If large prospective studies confirm these findings, then testing for this thrombogenic mutation should be considered in women and placental tissue from spontaneous abortuses and placentas with evidence of placental infarction. In addition to identifying individuals and families at risk for thrombosis, this information may help to improve our understanding of hemostasis and circulatory disturbances at the fetoplacental interface.