妊娠早期暴露低剂量华法林钠片后致胎儿畸形2例分析

doi:10.19803/j.1672-8629.20230074

中国药物警戒 ›› 2023, Vol. 20 ›› Issue (11): 1286-1289.
DOI: 10.19803/j.1672-8629.20230074

妊娠早期暴露低剂量华法林钠片后致胎儿畸形2例分析

杨彩华¹, 杨龙娜², 李小波^3,*

¹南方医科大学南方医院临床药学中心,广东广州 510515;
²广东省中医院珠海医院护理部,广东珠海 519020;
³珠海中西医结合医院药学部,广东珠海 519020

收稿日期:2023-02-13 出版日期:2023-11-15 发布日期:2023-11-13
通讯作者: ^*李小波,男,本科,副主任药师,临床药学。E-mail：330173675@163.com
作者简介:杨彩华,女,硕士,主管药师,妊娠期/哺乳期安全用药。
基金资助:
中国药学会科技开发中心项目[CMEI2022KPYJ (ZAMM)00601]

Two cases of fetal malformation after exposure to low dose warfarin sodium tablets in early pregnancy

YANG Caihua¹, YANG Longna², LI Xiaobo^3,*

¹Clinical Pharmacy Center, Nanfang Hospital,Southern Medical University, Guangzhou Guangdong 510515, China;
²Nursing Department of Zhuhai Hospital, Guangdong Provincial Hospital of Traditional Chinese Medicine, Zhuhai Guangdong 519020, China;
³Department of Pharmacy, Zhuhai Hospital of Integrated Traditional Chinese Medicine and Western Medicine, Zhuhai Guangdong 519020, China

Received:2023-02-13 Online:2023-11-15 Published:2023-11-13

摘要/Abstract

摘要： 目的探讨母体妊娠早期暴露于低剂量华法林钠片后导致胎儿畸形的影响因素及药物遗传学效应。方法报道2例心脏机械瓣膜置换术后妊娠女性服用低剂量（<5 mg·d^-1）华法林钠片抗凝治疗后出现胎儿唇腭裂和鼻骨发育短小的畸形病例,并综合文献分析胎儿畸形与低剂量华法林之间的药物相关性及其致畸分子机制。结果与结论 中国人群中,孕早期低剂量（<5 mg·d^-1）华法林暴露存在胎儿口面部畸形风险,其致畸性与母体华法林剂量、暴露时间窗和个体间差异具有相关性。文献资料显示个体间CYP2C9、VKORC1基因多态性和ayl sulfatase E基因突变等也可能起关键作用,应引起临床重视。

关键词: 华法林钠片, 妊娠, 低剂量, 唇腭裂, 鼻骨发育不全, 药品不良反应

Abstract: Objective To investigate the influencing factors and pharmacogenetic effects of fetal malformation caused by maternal exposure to low-dose warfarin sodium tablets during early pregnancy. Methods Two cases of fetal cleft lips and palates as well as short nasal bone development due to exposure to low-dose warfarin sodium tablets(<5 mg·d^-1) during early pregnancy for anticoagulation after mechanical valve replacement were reported. The possible drug correlations and teratogenic molecular mechanism between fetal malformation and low-dose warfarin were discussed based on related literature. Results and Conclusion In Chinese populations, low-dose warfarin exposure(<5 mg·d^-1) in early pregnancy can increase the risk of fetal oral-facial malformation, and its teratogenic mechanism may be correlated with the maternal warfarin dose, exposure time window and individual differences. Literature suggests that inter-individual CYP2C9, VKORC1 gene polymorphisms and AYL Sulfatase E gene mutations may also play a key role, which deserves clinical attention.

Key words: warfarin sodium tablets, pregnancy, low-dose, cleft lip and palate, nasal bone hypoplasia, adverse drug reaction

中图分类号:

R972
R994.11

杨彩华, 杨龙娜, 李小波. 妊娠早期暴露低剂量华法林钠片后致胎儿畸形2例分析[J]. 中国药物警戒, 2023, 20(11): 1286-1289.

YANG Caihua, YANG Longna, LI Xiaobo. Two cases of fetal malformation after exposure to low dose warfarin sodium tablets in early pregnancy[J]. Chinese Journal of Pharmacovigilance, 2023, 20(11): 1286-1289.

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妊娠早期暴露低剂量华法林钠片后致胎儿畸形2例分析

Two cases of fetal malformation after exposure to low dose warfarin sodium tablets in early pregnancy

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