基于病例报告文献对草药和膳食补充剂增强华法林抗凝作用的分析与评价

Analysis and evaluation on enhancement of anticoagulant effect of warfarin by herbal and dietary supplements based on case report literature

目的对病例报告文献报道的草药和膳食补充剂(HDS)增强华法林的抗凝作用进行分析和评价。方法检索国内外相关数据库(截至2021年10月10日),选择HDS与华法林相互作用致抗凝作用增强的病例报告文献。根据病例报告中患者国际标准化比值升高程度和出血事件发生情况评价HDS增强华法林抗凝作用的程度。根据HDS与华法林抗凝作用增强的因果关系评价结果、病例报告数量和其他证据(国家相关机构发布警告、临床研究、药代动力学/药效动力学研究、动物实验研究等),建立HDS与华法林相互作用可靠性评分标准,评价HDS增强华法林抗凝作用的可靠性。总得分≥9分为高度可靠,6~8分为较可靠,3~5分为可能可靠,≤2分为可疑可靠。结果共收集到41篇文献,涉及56例患者、26种HDS。轻度增加华法林抗凝作用的HDS有5种,包括当归、草木犀流浸液片、南瓜籽、鱼油和水飞蓟;中度者6种,包括生姜、芒果、蜂花粉、斯卡珀农葡萄、核桃和灰树花;重度者15种,包括蔓越莓、丹参、甘草、红花、蒲公英、枸杞、葡萄柚、洋甘菊、石榴汁、虾青素胶囊、苦艾、蜂王浆、越橘、红枣和贯叶连翘。增强华法林抗凝作用可靠性评价为高度可靠的HDS有1种,为蔓越莓(评分为11分);较可靠者8种,包括丹参、甘草、红花、蒲公英、枸杞、葡萄柚、洋甘菊和石榴汁(评分分别为8、7、7、7、7、6、6、6分);可能可靠者12种,包括当归、生姜、草木犀流浸液片、芒果、虾青素胶囊、蜂花粉、苦艾、蜂王浆、斯卡珀农葡萄、核桃、越橘和灰树花(评分分别为5、5、5、5、4、4、4、3、3、3、3、3分);可疑可靠者5种,包括南瓜籽、红枣、鱼油、水飞蓟和贯叶连翘(评分分别为2、2、2、0、-1分)。结论蔓越莓、丹参、甘草、红花、蒲公英、枸杞、葡萄柚、洋甘菊和石榴汁等HDS增强华法林抗凝作用的程度和可靠性均较高,应避免在华法林治疗期间使用。

Objective To analyze and evaluate the enhancement of anticoagulant effect of warfarin by herbal and dietary supplements(HDS)based on case report literature.Methods The case reports on enhancement of anticoagulant effect of warfarin by HDS were selected by searching the relevant databases at home and abroad(up to October 10,2021).The degree of enhancement of anticoagulant effect of warfarin by HDS was evaluated according to the increase of International Standardized Ratio and the occurrence of bleeding events in patients in the case reports.The reliability scoring standard of HDS-warfarin interaction was established according to the causatity evaluation results between HDS and enhancement of anticoagulant effect of warfarin,the number of case reports,and the other evidences(warnings issued by relevant national institutions,clinical studies,pharmacokinetic/pharmacodynamic studies,experimental animal studies,etc.)and the reliability of enhancement of anticoagulation effects of warfarin by HDS was evaluated.The reliability was evaluated as highly,relatively,possible,and suspicious reliable if the total score was≥9,6-8,3-5,and≤2 points,respectively.Results A total of 41 case reports were enrolled in the analysis,involving 56 patients and 26 kinds of HDS.Five kinds of HDS increased the anticoagulant effect of warfarin slightly,including Chinese angelica(Radix Angelicae Sinensis),melilotus extract tablets,pumpkin seed,fish oil,and milk thistle;6 kinds of HDS increased the anticoagulant effect of warfarin moderately,including ginger(Rhizoma Zingiberis Recens),mango,bee pollen,scarponon grape,Persian walnut,and grifola frondosa;and 15 kinds of HDS increased the anticoagulant effect of warfarin severely,including cranberry,danshen(Salvia miltiorrhiza),glycyrrhiza(Radix Glycyrrhizae),safflower(Flos Carthami),dandelion(Herba Taraxaci),Lyciumbar barum L.,grapefruit,matricaria chamomilla,pomegranate juice,astaxanthin,Artemisia absinthiu,royal jelly,bilberry(Vaccinium vitis-idaea),red dates,and St.John′s wort(Hypericum perforatum L.).The reliability of enhancement of anticoagulant effect of warfarin was evaluated as highly reliable in 1 kind of HDS,namely cranberry(11 points),relatively reliable in 8 kinds of HDS,including danshen,glycyrrhiza,saf-flower,dandelion,Lycium barbarum L.,grapefruit,matricaria chamomilla,and pomegranate juice(8,7,7,7,6,6,and 6 points,respectively),possibly reliable in 12 kinds of HDS,including Chinese angelica,ginger,melilotus extract tablets,mango,astaxanthin capsules,bee pollen,Artemisia absinthium,royal jelly,scarponon grape,Persian walnut,bilberry,and grifola frondosa(5,5,5,5,4,4,4,3,3,3,3,and 3 points,respectively),and suspicious reliable in 5 kinds of HDS,including pumpkin seed,red dates,fish oil,milk thistle,and St.John′s wort(2,2,2,0,and-1 points,respectively).Conclusions The degree and reliability of enhancement of anticoagulant effect of warfarin by cranberry,danshen,glycyrrhiza,safflower,dandelion,Lycium barbarum L,grapefruit,matricaria chamomilla,and pomegranate juice are higher,which should be avoided during warfarin therapy.