Howe A M, Oakes D J, Woodman P D, Webster W S
Department of Anatomy, University of Sydney, NSW, Australia.
Epilepsia. 1999 Jul;40(7):980-4. doi: 10.1111/j.1528-1157.1999.tb00806.x.
To determine whether anticonvulsant exposure during human pregnancy caused an increase of the abnormal form of prothrombin, known as PIVKA-II (prothrombin induced by vitamin K absence for factor II), and a decrease in total prothrombin, in the blood of the newborn.
Cord blood was collected from the placenta at the time of parturition from 12 women who had received anticonvulsant therapy during pregnancy and from 11 control women.
PIVKA-II was present in cord blood from control mothers at low or nondetectable levels. In the same samples, total prothrombin concentrations were approximately 50% of adult levels, but there was wide variation between individuals. Exposure to carbamazepine (CBZ) alone during pregnancy was associated with markedly increased PIVKA-II levels in four of six samples and decreased total prothrombin levels for the whole group. High PIVKA-II levels also were recorded in one cord blood sample from a mother who received phenytoin (PHT) and vigabatrin (VGB). Two cases of PHT alone and one of valproic acid (VPA) alone were not associated with increased PIVKA-II levels.
These results are consistent with the hypothesis that some anticonvulsants (particularly CBZ) interfere with vitamin K metabolism during pregnancy and may result in hematologic signs of vitamin K deficiency in the newborn.
确定人类孕期接触抗惊厥药物是否会导致新生儿血液中异常形式的凝血酶原(称为PIVKA-II,即维生素K缺乏诱导的凝血因子II)增加以及总凝血酶原减少。
从12名孕期接受抗惊厥治疗的女性和11名对照女性分娩时的胎盘采集脐带血。
对照母亲的脐带血中PIVKA-II含量低或检测不到。在相同样本中,总凝血酶原浓度约为成人水平的50%,但个体间差异很大。孕期单独接触卡马西平(CBZ)与六个样本中的四个样本中PIVKA-II水平显著升高以及整个组的总凝血酶原水平降低有关。在一名接受苯妥英(PHT)和氨己烯酸(VGB)治疗的母亲的一份脐带血样本中也记录到高PIVKA-II水平。单独使用PHT的两例和单独使用丙戊酸(VPA)的一例与PIVKA-II水平升高无关。
这些结果与以下假设一致,即某些抗惊厥药物(特别是CBZ)在孕期会干扰维生素K代谢,并可能导致新生儿出现维生素K缺乏的血液学体征。