A rising INR after a 'natural' joint remedy
A 58-year-old woman on warfarin for atrial fibrillation, stable at an INR of 2.5 for 8 months, attends the anticoagulation clinic with bleeding gums after brushing her teeth. Her INR today is 4.9. She has no melaena, no haematuria and no bruising beyond a small bruise on her forearm, and is haemodynamically stable. On questioning she reveals that 3 weeks ago she began a herbal mixture bought from a market stall for knee pain, which lists ginkgo and a high-dose fish oil, and she also started St John's wort capsules 2 weeks ago for low mood. She has not changed her warfarin dose, diet or alcohol intake, and has taken no new prescribed medicines.
1. Assess the likely contributors to this INR and explain the pharmacological reasoning behind each.
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Ginkgo: contains ginkgolides that inhibit platelet-activating factor and has been associated with bleeding, including with warfarin. It does not raise the INR itself, so it adds bleeding risk without the test showing it.
High-dose fish oil: omega-3 fatty acids reduce platelet aggregation and can prolong bleeding time at gram doses. Again, an additive bleeding effect rather than an INR effect.
St John's wort (Hypericum): a potent inducer of CYP3A4 and of P-glycoprotein. On its own it would be expected to increase warfarin metabolism and lower the INR. The INR rose anyway, which tells me the antiplatelet effects and any reduction in vitamin K intake from eating less because of knee pain are outweighing the induction, or that the product's actual content does not match the label. It also means the INR may fall sharply if she stops the St John's wort abruptly, so she needs closer monitoring either way.
Other explanations to exclude before blaming the herbs: missed or extra warfarin doses, a new medicine or antibiotic from another source, alcohol, acute illness, liver change, or a change in vitamin K-rich foods. The gum bleeding with an INR of 4.9 is minor but real, and the combination of a raised INR plus two antiplatelet-acting herbs is more than additive.
Causality judgement: temporal relationship, plausible mechanism for each product, no alternative cause found - probable for the combination, though the exact product cannot be verified because market-stall preparations are unregulated and often adulterated.
2. What is your management plan today, and why is stopping warfarin outright the wrong move?
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Today:
- She is stable with only minor bleeding: withhold one or two warfarin doses and recheck the INR in 2 to 3 days. Oral vitamin K is not needed for an INR of 4.9 without significant bleeding, and giving it would make her subtherapeutic and expose her to stroke risk; it is reserved for major bleeding or a much higher INR with bleeding risk factors.
- Examine for hidden bleeding and check haemoglobin, platelets and renal and liver function.
- Stop the ginkgo and fish oil product and stop the St John's wort - advise a tapered stop if she has been on it for weeks, and warn her that her INR may shift in either direction over the next 2 weeks.
- Offer effective alternatives for the knee: topical NSAID (with counselling about the interaction with warfarin and monitoring), paracetamol, physiotherapy.
- Bring her back for INRs at about 3 to 4 days, then weekly for 2 to 3 weeks.
Why not stop warfarin: her stroke risk from atrial fibrillation is unchanged and warfarin has a long half-life; abruptly stopping leaves her unprotected for days while the INR falls, trading a minor bleeding event for a potentially disabling stroke. The correct move is to control the interaction, not to remove the anticoagulant.
Also: review other medicines she buys - St John's wort reduces the effect of many drugs, including direct oral anticoagulants, ciclosporin and combined oral contraceptives - and document all herbal use in her record.
3. The same market stall also sells a 'honey and black seed' preparation marketed for diabetes. What quality and safety questions would you raise, and how would you counsel a patient who asks whether to take it?
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Quality questions:
- Unregistered product: no marketing authorisation, so there is no verified identity, purity, strength or manufacturing standard, and no recall mechanism if something goes wrong.
- Adulteration: herbal products for diabetes have repeatedly been found to contain undeclared conventional drugs such as sulfonylureas or metformin, which can cause hypoglycaemia and are dangerous if the patient's own medication doses are unknown.
- Contaminants: heavy metals (lead, arsenic, mercury) and microbial contamination are documented problems in unregulated herbal preparations.
- Label claims: 'natural' is not a synonym for safe or effective, and the label may not list everything in the jar.
Counselling:
- I would not recommend it, and I would explain why in plain language rather than dismissing it.
- If she insists on taking it, document it, warn her to watch for hypoglycaemia and to check her blood glucose, and warn about possible interaction with her prescribed therapy; do not let it replace proven treatment.
- Ask her to bring the container so the ingredients can be checked, and report a suspiciously effective or adulterated product to the regulatory authority.
Reasoning: in natural products the pharmacist's job is not to police belief but to protect the patient from an unquantified dose of an unknown substance - the risk is highest precisely where the product seems to work.