MethodsThe 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.
ResultsA 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, safflower, 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).
ConclusionsThe 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.
