Bruising, Dark Urine and an INR of 6.2 on Day 4 of Ciprofloxacin
Mr Hany, 68 years old and 74 kg, was admitted three days ago with fever, dysuria and flank pain. His history includes atrial fibrillation and heart failure with an ejection fraction of 38%. He has taken warfarin 5 mg every evening for six years, and his INR has stayed between 2.2 and 2.6 throughout that time. The medical resident prescribed oral ciprofloxacin 500 mg twice daily and continued the warfarin unchanged. At 17:40 on day 4, while helping him shave, the nurse notices bruising over both forearms, blood on his toothbrush and dark, tea-coloured urine. Observations: BP 126/78 mmHg, pulse 92 and irregular, respirations 18, temperature 37.1 °C. Blood results today: INR 6.2 (yesterday 3.1), haemoglobin 10.6 g/dL (baseline 12.9), platelets 195 × 10⁹/L, creatinine 1.4 mg/dL (baseline 1.1). The resident is scrubbed in theatre and cannot be reached for 40 minutes. Warfarin 5 mg is due at 18:00. Mr Hany asks for a razor and says he feels 'perfectly fine'.
1. Which drug interaction best explains the INR of 6.2, and what will you do in the next 30 minutes before the resident is reachable?
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The interaction. Ciprofloxacin is a well-recognised potentiator of warfarin. It inhibits cytochrome P450 enzymes that clear warfarin (notably CYP1A2 and CYP3A4, which handle the less potent R-enantiomer) and suppresses the gut flora that synthesise vitamin K. In a patient whose creatinine has already risen from 1.1 to 1.4 mg/dL, less drug and less metabolite are excreted, so the effect compounds. The result is the jump from 3.1 to 6.2 with clinical bleeding: bruising, gum bleeding and haematuria.
Next 30 minutes, before the resident answers:
- Hold the 18:00 warfarin dose. Do not administer it; another dose deepens the coagulopathy.
- Look for hidden bleeding: urine, stool, gums, IV puncture sites, abdominal girth, and a quick neurological check for headache, confusion or focal deficit.
- Remove bleeding risks: no IM injections, no rectal temperatures, no aspirin or NSAIDs, electric razor instead of the blade he requested, fall precautions.
- Escalate in parallel: telephone the resident and the on-call medical team, and if there is no answer within about 10 minutes, go to the nurse in charge and the medical director. The patient is bleeding on a supratherapeutic INR; this is not a 'wait for rounds' problem.
- Prepare: know where vitamin K is kept, have the reversal protocol to hand, and anticipate repeat INR, CBC and a group and screen.
- Document the findings, the time you held the dose and the time you called.
2. The resident later orders vitamin K 5 mg by slow intravenous injection. Explain the rationale, the administration safeguards and the monitoring that must follow.
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Rationale. Vitamin K restores gamma-carboxylation of clotting factors II, VII, IX and X, which warfarin has blocked. The intravenous route is chosen because this patient is actively bleeding and absorption is unreliable. Its onset is nevertheless slow (roughly 6–12 hours), so it does not replace volume resuscitation or, in major haemorrhage, prothrombin complex concentrate. Warn the team not to expect an immediate INR correction.
Administration safeguards.
- Give slowly, no faster than about 1 mg per minute, diluted as per protocol. Rapid IV vitamin K can cause an anaphylactoid reaction: flushing, chest tightness, hypotension.
- Keep the resuscitation trolley nearby and monitor pulse, BP and SpO2 during and after the injection.
- Check the prescription dose against the protocol. Five milligrams is a high-end dose for a bleeding patient; smaller doses (1–2 mg IV) are used when the aim is simply to lower the INR without overcorrection, and this man has atrial fibrillation with a thrombotic risk.
Monitoring afterwards.
- Repeat INR at the interval the protocol states, usually 6–12 hours; report the result and any further bleeding.
- Continue neurovascular and urine checks.
- Warn the team that he may be warfarin-resistant for several days, so the next doses need re-titration.
- Record the injection, the rate, and the observations in the notes.
3. What discharge teaching will you give Mr Hany before he leaves, and why does each point matter for him specifically?
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Medicines.
- Every prescriber, including the dentist and the pharmacist, must be told he takes warfarin. Antibiotics, antifungals, some painkillers and herbal products change the INR.
- Do not take aspirin, ibuprofen or other NSAIDs unless a doctor specifically approves them, because of the combined bleeding risk with warfarin.
- Never double a missed dose; record missed doses and tell the anticoagulation clinic.
Bleeding precautions.
- Use an electric razor and a soft toothbrush; use gloves for gardening.
- Report at once: black or bloody stool, red or dark urine, nosebleeds that will not stop, vomiting blood, unusual headache, or any fall to the head. A headache matters here because a supratherapeutic INR makes intracranial bleeding more likely.
- Carry an anticoagulant card or bracelet.
Monitoring and diet.
- Keep vitamin K-rich foods (spinach, broccoli, liver, green tea) consistent rather than avoiding them; sudden swings change the INR.
- Keep the INR appointments; after this episode the clinic will want him reviewed within a week.
Why it matters for him. He has already bled once on a drug interaction and has heart failure with reduced ejection fraction and atrial fibrillation, so both bleeding and clot are real dangers. He needs to understand that feeling well does not mean the INR is safe. Give the teaching in short chunks, ask him to repeat it back, and write it down in Arabic for him and his family.