Apixaban dose error and a bleeding duodenal ulcer in an elderly patient with atrial fibrillation
A 74-year-old woman with non-valvular atrial fibrillation (CHA2DS2-VASc 5, HAS-BLED 3) attends the emergency department with 2 days of melena and dizziness. She weighs 57 kg; serum creatinine is 1.6 mg/dL (eGFR 28 mL/min/1.73 m2) and has been stable for a year. Her medications are apixaban 5 mg twice daily, aspirin 81 mg daily (begun after a PCI 3 years ago), atorvastatin 40 mg, bisoprolol 5 mg and amlodipine 5 mg. Blood pressure is 105/65 mmHg, heart rate 96/min, haemoglobin 7.8 g/dL, platelets 210 x 10^9/L, INR 1.1. Upper endoscopy shows a 1.5 cm duodenal ulcer with a visible vessel, treated with adrenaline injection and clips; there is no active bleeding at the end of the procedure. The cardiology team asks when anticoagulation can be restarted and whether the apixaban dose was correct. There has been no recent coronary event, and the patient has taken no NSAIDs.
1. Using the apixaban dose-reduction criteria, judge whether 5 mg twice daily was appropriate for this patient and quantify the bleeding risk factors that were present before this admission.
Read the worked answer
Apixaban dose reduction requires two of three criteria: age 80 years or older, weight 60 kg or less, serum creatinine 1.5 mg/dL or more.
This patient meets two: weight 57 kg and creatinine 1.6 mg/dL. Age 74 is not a criterion. Therefore the correct dose is 2.5 mg twice daily, and 5 mg twice daily was a twofold overdose sustained over a long period. This is a prescribing error, not a drug failure, and it should be reported through the pharmacovigilance system.
Modifiable risks that were present before the bleed:
- Aspirin 81 mg continued 3 years after PCI with no recent coronary event - antiplatelet therapy adds gastrointestinal bleeding without a current indication once the high-risk period after stenting has passed.
- HAS-BLED 3 (age over 65, bleeding history, hypertension/renal impairment) indicates a high baseline risk that should have prompted review of the aspirin and confirmation of the apixaban dose.
- CKD with eGFR 28 reduces apixaban clearance modestly, reinforcing the lower dose.
Withholding anticoagulation entirely is not the solution: CHA2DS2-VASc 5 predicts a high annual stroke risk, and correct-dose apixaban still gives net clinical benefit. The error was the dose, not the decision to anticoagulate.
2. Recommend a plan for restarting oral anticoagulation after endoscopic haemostasis, including timing, agent, dose and the competing risks. Include the non-anticoagulant measures you would add before discharge.
Read the worked answer
With a visible vessel (high-risk stigmata), restart oral anticoagulation after 7-14 days, not immediately and not beyond 2 weeks. Immediate restart increases rebleeding; prolonged withdrawal increases stroke risk, which is substantial at CHA2DS2-VASc 5.
Plan:
- Restart apixaban 2.5 mg twice daily around day 7, after confirming a stable haemoglobin and no recurrent bleeding.
- Do not restart aspirin - it was for secondary prevention after a remote PCI and there is no current indication.
- Start a proton pump inhibitor, e.g. pantoprazole 40 mg twice daily for at least 8 weeks, then once daily.
- Test for H. pylori and treat if positive; this is a major cause of recurrent ulcer bleeding.
- Do not switch to warfarin: it has a higher intracranial haemorrhage risk, needs monitoring, and the patient is already correctly dose-reduced on a direct oral anticoagulant.
- Counsel on melena, haematemesis, dizziness and adherence; check full blood count at 2 and 4 weeks.
If bleeding recurs, hold the anticoagulant, resuscitate, and use prothrombin complex concentrate (or andexanet alfa if available). Vitamin K does not reverse apixaban. Document the dose-reduction rationale in the chart so that a future prescriber does not "correct" it back to 5 mg.