Failing to ask clients about any herbs their pet has received before surgery could lead to bleeding disasters during surgery. Specifically, botanicals that interfere with clotting could transform an otherwise routine surgery into a frustrating and lengthy exercise.1 False Sense of Security While the true clinical impact remains clouded by lack of controlled research in both veterinary and human patients,2 this paucity of safety information may be creating a self-perpetuating cycle of false-negative information.3 The unregulated and untested nature of veterinary plant-based products amplifies uncertainties over product strength, potential misidentification, adulteration and species-specific or idiosyncratic variations in drug metabolism or effects.4 In particular, products with a multiplicity of ingredients, such as Chinese herbal formulations, especially when administered chronically, exhibit a disproportionately greater percentage and severity of side effects, compared to single-herb supplements.5,6,7 Harmful drug-herb interactions involving mixtures of herbs heighten the hurdles of identifying the source of the interaction. Mechanisms by which herbs may influence bleeding include direct pharmacologic actions and indirect interactions.8 Indirect (namely, herb-drug) interactions involve either pharmacodynamic or pharmacokinetic influences. Antiplatelet Effects From top to botton, garic, ginger, ginko and ginseng. Veterinary patients ingesting herbs for longstanding conditions such as arthritis and cancer build higher blood levels. Arthritis remedies typically interfere with arachidonic acid metabolism and therefore may likewise inhibit platelet aggregation, either by inhibiting platelet activating factor (PAF) binding or by limiting production of other mediators, such as thromboxanes, adenosine or prostaglandins.9 Bleeding tendencies increase with non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen.10 Implicated herbs include ginkgo (Ginkgo biloba), garlic (Allium sativum), ginger (Zingiber officinale)11 and ginseng (Panax ginseng), known as the “4 Gs.” Others include meadowsweet (Filipendula ulmaria), willow bark (Salix alba), dong guai (Angelica sinensis), turmeric (Curcuma longa), bilberry (Vaccinium myrtillus) and feverfew (Tanacetum parthenium). Warfarin-herb Interactions Concerns multiply when patients receive warfarin. Originally derived from the sweet clover plant, warfarin interferes with the ability of vitamin K to form the vitamin K-dependent coagulation factors II, VII, IX and X, as well as the anticoagulant proteins C and S.12,13 Achieving optimal therapeutic concentrations requires close monitoring and multiple challenges make it difficult to maintain stable prothrombin international normalized ratios (PT-INR). Many factors alter INRs, including pharmacogenomic expression of enzyme activities affecting drug metabolism, dietary vitamin K intake, other medications, patient age, the presence of comorbid diseases and herbs.14,15 Coumarins appear ubiquitously in green plants, though some herbs antagonize vitamin K more strongly than others.16 Lists of herbs have drawn concern; popular plants in veterinary products include angelica, arnica, bromelain, chamomile, corydalis yanhuso, danshen, devil’s claw, fenugreek, feverfew, garlic, ginger, ginseng, green tea, licorice, meadowsweet, papain, passionflower, red clover, reishi mushroom, skullcap, turmeric and willow bark.17 Although ginseng appears here, the term “ginseng” actually refers to several species, each with different amounts anticoagulant compounds18. Paradoxical effects are also possible; one study showed that American ginseng actually reduced warfarin’s anticoagulant effect.19 Avoiding Surprises It may take a week to restore normal hemostasis after stopping garlic, 1.5 days after ginkgo, and 24 hours after ginseng.20 It seems prudent, therefore, for veterinary patients to refrain from anticoagulant herbs at least several days before elective surgery. <HOME> Dr. Robinson, DO, DVM, MS, FAAMA, oversees complementary medicine education at Colorado State University. Footnotes: 1. Trepanier LA. Potential interactions between non-steroidal anti-inflammatory drugs and other drugs. Journal of Veterinary Emergency and Critical Care. 2005;15(4):248-253. 2. Beckert BW, Concannon MJ, Henry SL, et al. The effect of herbal medicines on platelet function: an in vivo experiment and review of the literature. Plast Reconstr Surg. 2007;120:2044-2050. 3. Palmer ME. Effect of dietary supplements on hemostasis: a case of bleeding in context of research and surveillance. Thrombosis Research. 2005;117:33-38. 4. Fugh-Berman A. Herb-drug interactions. The Lancet. 2000;355:134-138. 5. Palmer ME. Effect of dietary supplements on hemostasis: a case of bleeding in context of research and surveillance. Thrombosis Research. 2005;117:33-38. 6. Gou YL, Ho ALS, Rowlands DK, et al. Effects of Bak Foong Pill on blood coagulation and platelet aggregation. Biol Pharm Bull. 2003;26(2):241-246. 7. Makino T, Wakushima H, Okamoto T, et al. Effects of Kangen-karyu on coagulation system and platelet aggregation in mice. Biol Pharm Bull. 2002;25(4):523-525. 8. Basila D and Yuan C-S. Effects of dietary supplements on coagulation and platelet function. Thrombosis Research. 2005;117:49-53. 9. Abebe W. Herbal medication: potential for adverse interactions with analgesic drugs. Journal of Clinical Pharmacy and Therapeutics. 2002;27:391-401. 10. Abebe W. Herbal medication: potential for adverse interactions with analgesic drugs. Journal of Clinical Pharmacy and Therapeutics. 2002;27:391-401. 11. Kruth P, Brosi E, Fux R, et al. Ginger-associated overanticoagulation by phenprocoumon. The Annals of Pharmacotherapy. 2004;38:257-260. 12. Samuels N. Herbal remedies and anticoagulant therapy. Thromb Haemost. 2005;93:3-7. 13. Monnet E and Morgan MR. Effect of three loading doses of warfarin on the international normalized ratio for dogs. Am J Vet Res. 2000;61:48-50. 14. Wittkowsky AK. A systematic review and inventory of supplement effects on warfarin and other anticoagulants. Thrombosis Research. 2005;117:81-86. 15. Yuan C-S, Wei G, Dey L, et al. Brief communication: American Ginseng reduces warfarin’s effect in healthy patients – a randomized, controlled trial. Ann Intern Med. 2004;141:23-27. 16. Samuels N. Herbal remedies and anticoagulant therapy. Thromb Haemost. 2005;93:3-7. 17. Samuels N. Herbal remedies and anticoagulant therapy. Thromb Haemost. 2005;93:3-7. 18. Cheng TO. Ginseng and other herbal medicines that interact with warfarin. International Journal of Cardiology. 2005;104:227. 19. Yuan C-S, Wei G, Dey L, et al. Brief communication: American Ginseng reduces warfarin’s effect in healthy patients – a randomized, controlled trial. Ann Intern Med. 2004;141:23-27. 20. Kuczkowski KM. Can alternative medicine alter the way we do anesthesia? Ann Fr Anesth Reanim. 2007 May;26(5):468-9. ---------------------------------------------------------------- Click here to read more from Complementary Medicine.
