Pati S, Helmbrecht G D
Department of Obstetrics and Gynecology, Georgetown University Medical Center, Washington, DC 20007.
Reprod Toxicol. 1994 Mar-Apr;8(2):115-20. doi: 10.1016/0890-6238(94)90018-3.
The warfarin embryopathy is a well-defined complex of fetal anomalies generally accepted to result from first trimester exposure. Optic atrophy and dilation of the cerebral cerebral ventricles associated with blindness, microcephaly, and mental retardation have been reported following second and third trimester exposure. In contrast to the consistent clinical features observed in the warfarin embryopathy, the CNS effects seen in fetuses exposed in the later trimesters share little in terms of specific lesion or long-term clinical outcome. A case of schizencephaly in a coumadin-exposed fetus is presented. This report offers supportive evidence that the CNS sequellae of this agent are the result of vascular accident and hemorrhage, not a direct effect on CNS morphogenesis. The molecular basis for the adverse effects of warfarin derivatives on the fetus are reviewed. Warfarin derivatives exert both their embryopathic and their fetopathic effects via pharmacologic action: inhibition of gamma carboxylation of osteocalcin and a similar carboxylation of the vitamin K dependent clotting factors. Therefore, we believe that warfarin exposure in the second or third trimesters of pregnancy is equally dangerous to the fetus as that in the first. Heparin may be a superior alternative to warfarin for the prevention of thromboembolic disease in pregnant women with cardiac valve prostheses.
华法林胚胎病是一种明确的胎儿异常综合征，普遍认为是由于孕早期接触华法林所致。有报道称，在孕中期和孕晚期接触华法林后，会出现视神经萎缩、脑室扩张，并伴有失明、小头畸形和智力发育迟缓。与华法林胚胎病中观察到的一致临床特征不同，孕晚期接触华法林的胎儿出现的中枢神经系统影响在特定病变或长期临床结局方面几乎没有共同之处。本文报告了一例暴露于香豆素的胎儿患脑裂畸形的病例。该报告提供了支持性证据，表明该药物的中枢神经系统后遗症是血管意外和出血的结果，而非对中枢神经系统形态发生的直接影响。本文回顾了华法林衍生物对胎儿产生不良影响的分子基础。华法林衍生物通过药理作用发挥其胚胎病和胎儿病作用：抑制骨钙素的γ羧化以及维生素K依赖凝血因子的类似羧化。因此，我们认为孕期第二或第三阶段接触华法林对胎儿同样危险。对于有心脏瓣膜假体的孕妇，肝素可能是预防血栓栓塞性疾病优于华法林的替代药物。
