Kupferminc M J, Eldor A, Steinman N, Many A, Bar-Am A, Jaffa A, Fait G, Lessing J B
Department of Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Israel.
N Engl J Med. 1999 Jan 7;340(1):9-13. doi: 10.1056/NEJM199901073400102.
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.
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.
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).
Women with serious obstetrical complications have an increased incidence of mutations predisposing them to thrombosis and other inherited and acquired forms of thrombophilia.
诸如重度子痫前期、胎盘早剥、胎儿生长受限和死产等产科并发症与绒毛间隙或螺旋动脉血栓形成及胎盘灌注不足有关。这些并发症是否与血栓形成倾向突变频率增加相关尚不清楚。
我们研究了110例患有上述产科并发症之一的女性和110例有一次或多次正常妊娠的女性。在分娩后数天对这些女性进行检测，以确定因子V基因第1691位核苷酸（校正后）鸟嘌呤突变为腺嘌呤（因子V莱顿突变）、编码亚甲基四氢叶酸还原酶基因第677位核苷酸胞嘧啶突变为胸腺嘧啶以及凝血酶原基因第20210位核苷酸鸟嘌呤突变为腺嘌呤。在分娩后两到三个月对这些女性进行检测，以确定蛋白C、蛋白S或抗凝血酶III缺乏以及是否存在抗心磷脂抗体。
在患有产科并发症的女性中有22例检测到因子V基因第（校正后）1691位核苷酸突变，而在有正常妊娠的女性中有7例检测到（分别为20%和6%；P = 0.003）。与9例无并发症女性相比，有24例有并发症的女性在编码亚甲基四氢叶酸还原酶基因的C677T突变中为纯合子（分别为22%和8%；P = 0.005）。在患有并发症的11例女性中发现凝血酶原基因的G20210A突变，而在无并发症的3例女性中发现（分别为10%和3%；P = 0.03）。总体而言，57例患有产科并发症的女性有血栓形成倾向突变，而有正常妊娠的女性中有19例（分别为52%和17%；P<0.0０1）。与1例有正常妊娠的女性相比，在另外14例有并发症的女性中检测到蛋白S、蛋白C或抗凝血酶III缺乏或抗心磷脂抗体（分别为13%和1%；P<0.0０1）。
患有严重产科并发症的女性发生使她们易患血栓形成及其他遗传性和获得性血栓形成倾向形式的突变的发生率增加。
