322例丙戊酸致纤维蛋白原降低文献分析

Literature Analysis on 322 Cases of Fibrinogen Reduction Induced by Valproate

目的:探讨丙戊酸致纤维蛋白原降低的临床特点、发生机制及防治措施,为临床合理用药提供依据。方法:收集1990～2018年国内外发表的关于丙戊酸致纤维蛋白原降低的文献,按照患者性别、年龄、用药情况、不良反应发生的时间、临床表现及处理方法等进行统计分析。结果:共有11篇文献纳入统计,涉及322例患者,其中儿童构成比(52. 17%)高于成人,男性构成比(72. 58%)高于女性。丙戊酸给药途径及其血药浓度对不良反应发生的影响尚未见明确相关性。纤维蛋白原降低通常发生在用药4 d后,减量、停药或给予补充纤维蛋白原可使体内纤维蛋白原水平恢复正常,最快3 d恢复。两例患者出现出血症状。结论:正常剂量丙戊酸可致纤维蛋白原降低,但影响其发生的因素有待进一步确定,建议在应用丙戊酸治疗期间密切监测患者纤维蛋白原含量变化,避免严重临床事件发生。

Objective:To find out the clinical features machanism and preventive measure of fibrinogen reduction induced by valproate to provide reference for its clinically safe application.Methods:Domestic and foreign case reports about fibrinogen decrease induced by valproate during 1990 and 2018 were collected,and all the literatures were analyzed in aspects of gender,age,drug usage and dosage,the time of ADR occurred,clinical manifestation and treatment.Results:A total of 11 articles involving 322 patients were included in the statistics,among them,the proportion of children was higher than adults,and men was higher than women.male were the main population.No clear correlation between the effect of valproic acid administration route and its blood concentration on the occurrence of adverse reactions was found.Fibrinogen reduction usually occurred after 4-days treatment,reducing dosage,withdrawal or supplementation of fibrinogen could restore the level to the normal range,and the fastest recovery was within 3 days.Two patients showed bleeding symptoms.Conclusion:Normal dosage of valproate can reduce fibrinogen,and the factors affecting the occurrence need to be further determined.It is recommended that patients treated with valproate should be closely monitored the changes of fibrinogen content during the medication to avoid serious clinical events.