INR 8.5 after interacting antibiotics in an older adult who falls
Mrs E is an 81-year-old woman with permanent atrial fibrillation, hypertension and mild cognitive impairment. She lives alone and has had two falls in the last six months, neither causing injury. Her warfarin dose has been stable at 4 mg daily for two years, with INR 2.4–2.8. Four days ago an out-of-hours GP prescribed clarithromycin 500 mg twice daily for a chest infection and fluconazole 150 mg for oral thrush. She presents to the practice with gum bleeding and extensive bruising. INR is 8.5, haemoglobin 105 g/L, platelets 180 × 10⁹/L, creatinine 130 µmol/L (eGFR 32), and she is haemodynamically stable with no melaena or haematuria. She is unsure why she was given the tablets and has continued her usual warfarin. Her daughter asks whether she should stop warfarin permanently because of the falls.
1. Outline your immediate management of the INR and bleeding, including what not to give.
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Immediate management. She has a high INR with minor bleeding, not major haemorrhage. Stop warfarin. Give vitamin K 1–2 mg IV (or 2–5 mg oral) according to local protocol; use the IV route if there is any concern about absorption. Do not give fresh frozen plasma or prothrombin complex concentrate unless there is major bleeding or she becomes unstable - they are unnecessary and thrombotic here. Check FBC, renal and liver function, and repeat INR in 24 hours. Monitor for melaena, haematuria and neurological symptoms. Treat anaemia only if symptomatic; her Hb is stable at 105 g/L.
Key reasoning. The INR is high because of a drug interaction, not because she needs a permanent dose change. Reversal should be proportionate. Over-treatment with PCC can cause thrombosis; under-treatment risks bleeding. Document the indication and the plan.
2. Review the prescribing and interaction; what would you change and how would you communicate it?
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Interaction. Clarithromycin and fluconazole both inhibit warfarin metabolism, and fluconazole is a potent CYP2C9 inhibitor; the combination is a predictable cause of a raised INR. The out-of-hours prescriber may not have seen the warfarin. Stop both if possible. For the chest infection, choose an antibiotic with less interaction (e.g. amoxicillin or doxycycline, depending on microbiology); for oral thrush, consider topical nystatin or a single low-dose fluconazole with INR monitoring. Tell the pharmacy and update the record with an interaction alert. Give her a written anticoagulant alert card and teach-back advice: ask about new medicines, avoid NSAIDs and aspirin, and report bleeding.
Future. Once the INR is safe, restart warfarin at her usual dose and recheck in 2–3 days. Consider whether a DOAC would be safer, but note her eGFR 32 and the need for dose adjustment.
3. How would you address the daughter's question about falls and anticoagulation?
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Falls and anticoagulation. Falls alone are not a reason to stop anticoagulation. Her stroke risk is high (CHA2DS2-VASc at least 4: age 81, hypertension, female sex, and possibly more), and the absolute stroke risk outweighs the risk of a fall-related bleed. Stopping warfarin would leave her at risk of a disabling stroke.
What to do instead. Address the falls: review sedatives and antihypertensives, check vision, gait and balance, home hazards, and consider a falls clinic. Reassess her bleeding risk and use the lowest effective anticoagulant. Discuss a DOAC (apixaban is often preferred in frailty) but check renal function and dose criteria. Explain the numbers to her daughter, acknowledge her concern, and agree a plan. Document the discussion and offer a follow-up. If she lacks capacity for this decision, hold a best-interests meeting.