N Engl J Med 1999, 340: 9-13
Kupferminc,M.J.; Eldor,A.; Steinman,N.; Many,A.; Bar-Am,A.; Jaffa,A.; Fait,G.; Lessing,J.B.
BACKGROUND: Obstetrical complications such as severe preeclampsia, abruptio
placentae, fetal growth retardation, and stillbirth are associated with intervillous or spiral-artery
thrombosis and inadequate placental perfusion. Whether these complications are associated with an increased
frequency of thrombophilic mutations is not known.
METHODS: We studied 110 women who had one of the above-mentioned obstetrical
complications and 110 women who had one or more normal pregnancies. The women were tested several days after
delivery for the mutation of guanine to adenine at nucleotide 1691 [corrected]
in the factor V gene (factor V Leiden), the mutation of cytosine to thymine at nucleotide 677 in the gene
encoding methylenetetrahydrofolate reductase, and the mutation of guanine to adenine at nucleotide 20210 in
the prothrombin gene. Two to three months after delivery the women were tested for deficiency of protein C,
protein S, or antithrombin III and for the presence of anticardiolipin antibodies.
RESULTS: The mutation at nucleotide 1691 [corrected] in the factor V gene was
detected in 22 of the women with obstetrical complications and in 7 of the women with normal pregnancies
(20 percent and 6 percent, respectively; P=0.003). Twenty-four women with complications, as compared with
nine women without complications, were homozygous for the C677T mutation in the gene encoding
methylenetetrahydrofolate reductase (22 percent and 8 percent,
respectively; P=0.005). The G20210A mutation in the prothrombin gene was found in 11 women with
complications as compared with 3 women without complications (10 percent and 3 percent, respectively; P=0.03).
Overall, 57 women with obstetrical complications had a thrombophilic mutation, as compared with 19 women
with normal pregnancies (52 percent and 17 percent, respectively; P<0.001). Deficiency of protein S,
protein C, or antithrombin III or anticardiolipin antibodies were detected in an additional 14 women with
complications, as compared with 1 woman with a normal pregnancy (13 percent and 1 percent, respectively; P<0.001).
CONCLUSIONS: Women with serious obstetrical complications have an increased incidence of mutations
predisposing them to thrombosis and other inherited and acquired forms of thrombophilia.