Case studies · Pharmacology · 30 October 2026

Warfarin toxicity case study

The case

Patient: Mr. R, 68‑year‑old male, retired accountant

Presenting complaint: Bruising over the trunk and spontaneous gross hematuria for 3 days

History of presenting illness:

• The bruises started as small, painless purpura on the abdomen and have progressively enlarged, now involving the chest and upper thighs.
• He noticed pink‑red urine on the second day, which has become darker (tea‑coloured) and is associated with mild dysuria.
• No history of trauma, falls, or recent invasive procedures.
• He reports a mild headache but denies focal neurological deficits, vomiting, or visual changes.

Past medical history:

• Non‑valvular atrial fibrillation (diagnosed 4 years ago) – on warfarin 5 mg daily (dose unchanged).
• Hypertension – on amlodipine 5 mg daily.
• Type 2 diabetes mellitus – on metformin 500 mg BID.

Drug history (last 2 weeks):

• Completed a 7‑day course of metronidazole 500 mg TID for diverticulitis, finished 4 days ago.
• Over‑the‑counter ibuprofen 400 mg TID for knee pain for the past 5 days.

Family/social history:

• Father died of myocardial infarction at 72 y.
• No known bleeding disorders in the family.
• Non‑smoker, occasional wine (1–2 glasses/week).

Examination:

Initial investigations (all performed on admission):

Questions

1. What is the most likely diagnosis?
2. Which clinical and laboratory findings point toward this diagnosis, and why?
3. List the investigations required to assess the severity and possible source of bleeding in a patient on warfarin.
4. Outline the immediate management plan according to the latest (2023) American College of Cardiology/American Heart Association (ACC/AHA) and 2022 NICE guidelines for warfarin‑associated major bleeding.
5. What are the potential complications of warfarin toxicity, and how should they be monitored during treatment?

Answers

1. What is the most likely diagnosis?

Warfarin‑associated major bleeding (over‑anticoagulation) – supratherapeutic INR with clinically evident hemorrhage.

The INR of 6.5 is far above the therapeutic range for atrial fibrillation (2.0–3.0). The presence of spontaneous ecchymoses and gross hematuria fulfills the definition of a major bleed as per the International Society on Thrombosis and Haemostasis (ISTH):

• Fatal bleeding, or
• Symptomatic bleeding in a critical area/organ, or
• Bleeding causing a fall in Hb ≥ 2 g/dL, or
• Bleeding leading to transfusion of ≥ 2 units of packed red cells.

In this case, the Hb has dropped to 9.2 g/dL (baseline unknown but likely > 12 g/dL) and the patient has overt bleeding, meeting the criteria.

2. Which clinical and laboratory findings point toward this diagnosis, and why?

3. List the investigations required to assess the severity and possible source of bleeding in a patient on warfarin.

4. Outline the immediate management plan according to the latest (2023) ACC/AHA and 2022 NICE guidelines for warfarin‑associated major bleeding.

Step 1 – Stop warfarin

• Discontinue warfarin immediately. Document the time of last dose.

Step 2 – Assess need for rapid reversal

• Indications for urgent reversal (ACC/AHA 2023): intracranial hemorrhage, life‑threatening bleeding, or INR ≥ 4 with major bleed.
• In this patient: INR = 6.5 with major bleeding → urgent reversal required.

Step 3 – Administer vitamin K

• Route: Intravenous (IV) infusion (preferred for rapid effect).
• Dose: 10 mg IV over 30 minutes (per 2022 NICE “Warfarin reversal” guideline).
• Rationale: Restores hepatic synthesis of vitamin K‑dependent clotting factors (II, VII, IX, X). Effect begins in 6–12 h; full effect 24 h.

Step 4 – Provide clotting factor replacement

• Preferred: PCC because of rapid INR normalization, low volume, and lower risk of transfusion‑related lung injury.
• Adjunct: If PCC not immediately available, give FFP while arranging PCC.

Step 5 – Supportive care

• Transfusion of packed red blood cells (PRBCs) if Hb < 8 g/dL or symptomatic anemia (tachycardia, hypotension). Target Hb ≥ 8–9 g/dL.
• Fluid resuscitation with isotonic crystalloids to maintain MAP ≥ 65 mm Hg.
• Analgesia with acetaminophen (avoid NSAIDs).

Step 6 – Monitor

• INR at 30 min, 1 h, then every 6 h until < 1.5, then daily until stable.
• Hemoglobin every 6 h for the first 24 h, then daily.
• Vital signs continuously for the first 2 h, then q4h.
• Urine output ≥ 0.5 mL/kg/h (≈ 35 mL/h for a 70‑kg adult).

Step 7 – Re‑initiate anticoagulation (if indicated)

• According to ACC/AHA 2023, for atrial fibrillation with high thrombo‑embolic risk (CHA₂DS₂‑VASc ≥ 2), restart oral anticoagulation after bleeding is controlled and the cause addressed, typically ≥ 7 days after major bleed, using a direct oral anticoagulant (DOAC) if no contraindications.
• If warfarin must be resumed, start at a reduced dose (e.g., 2 mg) with daily INR monitoring until therapeutic range achieved.

Step 8 – Address precipitating factors

• Discontinue interacting drugs: Stop ibuprofen; counsel on avoiding over‑the‑counter NSAIDs.
• Review antibiotic use: Metronidazole can increase warfarin effect; consider alternative agents in future.

Step 9 – Patient education & follow‑up

• Provide written instructions on diet (consistent vitamin K intake), medication adherence, and signs of bleeding.
• Arrange INR clinic visit within 2–3 days of discharge, then weekly until stable.

5. What are the potential complications of warfarin toxicity, and how should they be monitored during treatment?

Monitoring schedule (first 48 h after reversal):

• INR: 0.5 h, 1 h, 6 h, 12 h, then every 12 h.
• Hb/Hct: Every 6 h.
• Neurological exam: Every 2 h.
• Urine output & colour: Hourly charting.
• Fluid balance: Input‑output chart; watch for signs of overload (JVD, crackles).

Key learning points

• Warfarin toxicity is defined by an INR > 5.0 and clinically evident bleeding; an INR ≥ 6.0 is a medical emergency.
• Drug–drug interactions (e.g., metronidazole, NSAIDs) and acute illnesses are the most common precipitants of

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