Bleeding After Starting Warfarin for Atrial Fibrillation
A 74-year-old woman with atrial fibrillation is started on warfarin. Her baseline INR is 1.0. She is also on amiodarone for rhythm control and has chronic kidney disease (eGFR 35 mL/min/1.73m²). Ten days later, she presents with gum bleeding and bruising. Her INR is 6.8. She has no signs of major bleeding, but her haemoglobin has dropped from 125 g/L to 105 g/L. She is haemodynamically stable. The haematology laboratory reports that the thromboplastin reagent used has an ISI of 1.1, and the local target INR for atrial fibrillation is 2.0–3.0.
1. Explain the factors that contributed to the supratherapeutic INR and outline your immediate management.
Read the worked answer
Several factors interact. Warfarin inhibits vitamin K epoxide reductase, reducing synthesis of functional factors II, VII, IX, and X. Amiodarone inhibits CYP2C9, the main enzyme metabolising S-warfarin, so it increases warfarin effect. Chronic kidney disease reduces clearance of warfarin metabolites and may impair vitamin K recycling, further elevating INR. The patient's age and low body weight may also increase sensitivity. The ISI of 1.1 means the thromboplastin reagent is close to the international reference, so the INR is reliable. Immediate management: because there is no major bleeding, withhold warfarin and give vitamin K1 (phytomenadione) 1–2 mg orally or intravenously. If there were major bleeding, prothrombin complex concentrate would be indicated. Recheck INR in 24 hours. The drop in haemoglobin suggests some blood loss, so monitor for concealed bleeding. Once INR is therapeutic, restart warfarin at a lower dose, review interacting drugs (consider switching amiodarone if possible), and educate the patient. The judgement is to recognise the drug interaction and renal impairment as drivers, and to avoid overcorrecting with large doses of vitamin K that could cause warfarin resistance.
2. How would you adjust her anticoagulation strategy in the longer term, and what monitoring would you recommend?
Read the worked answer
Long-term, the goal is stable anticoagulation with the lowest effective dose. Warfarin can be continued with careful dose titration, but the amiodarone interaction will persist. A direct oral anticoagulant (DOAC) such as apixaban or rivaroxaban might be considered, but her eGFR of 35 mL/min/1.73m² means dose adjustment is needed and some DOACs are contraindicated or require caution. Apixaban is often preferred in renal impairment. However, DOACs are not without bleeding risk, and the patient has already shown sensitivity. If warfarin is continued, target INR 2.0–3.0, with more frequent monitoring initially (twice weekly until stable, then every 4–6 weeks). Educate her about avoiding over-the-counter NSAIDs and alcohol binges, and about consistent vitamin K intake. The judgement is to balance stroke prevention against bleeding risk, using risk scores (CHA2DS2-VASc and HAS-BLED) and shared decision-making. The recent bleed and drop in haemoglobin should prompt a review of whether the benefit of anticoagulation still outweighs the risk, and whether a left atrial appendage occlusion device might be considered if anticoagulation is deemed too risky.