A 45-year-old woman with hepatic cirrhosis (Child–Pugh Class B) is started on warfarin 5 mg daily for atrial fibrillation. Her baseline INR is 1.2. After 3 days, her INR is 4.8 and she is asymptomatic. What is the most appropriate immediate action?

Explanation

## Warfarin Pharmacokinetics in Hepatic Impairment **Key Point:** Warfarin is metabolized by hepatic cytochrome P450 enzymes (primarily CYP2C9). In cirrhosis, reduced hepatic synthetic function and enzyme activity prolong warfarin half-life, increase bioavailability, and elevate INR disproportionately even at standard doses. ### Warfarin Metabolism & Cirrhosis | Hepatic Status | Warfarin Clearance | INR Response | Management | |---|---|---|---| | Normal | Normal (40–50 h half-life) | Predictable | Standard dosing | | Mild impairment (Child A) | Mildly reduced | Increased sensitivity | Reduce dose 20–30% | | Moderate impairment (Child B) | Significantly reduced | Marked sensitivity | Reduce dose 30–50%; close monitoring | | Severe impairment (Child C) | Severely reduced | Unpredictable, high risk | Avoid if possible; use alternative | **High-Yield:** This patient has Child–Pugh Class B cirrhosis and achieved supratherapeutic INR (4.8) after just 3 days on standard dosing. This indicates severe warfarin sensitivity due to impaired hepatic metabolism. ### Management Algorithm for Supratherapeutic INR (No Bleeding) ```mermaid flowchart TD A[INR > therapeutic, asymptomatic]:::outcome --> B{INR level?}:::decision B -->|4.5-10| C[Hold warfarin]:::action C --> D[Recheck INR in 24 h]:::action D --> E[Resume at lower dose when INR in range]:::action B -->|> 10| F[Hold warfarin + Vitamin K 2.5-5 mg PO]:::action F --> G[Recheck INR in 24 h]:::action ``` **Clinical Pearl:** In asymptomatic patients with INR 4.5–10, holding warfarin and rechecking in 24 hours is safer and more physiologic than giving vitamin K (which causes resistance for 7–10 days) or FFP (which is reserved for bleeding or INR >10). **Warning:** Do NOT give vitamin K 10 mg IV in this scenario — it is excessive, causes warfarin resistance, and makes future anticoagulation difficult. Reserve high-dose vitamin K for INR >10 or active bleeding. **Tip:** Cirrhotic patients on warfarin require baseline dose reduction (30–50% of normal) and more frequent INR monitoring (every 2–3 days initially, then weekly) to avoid over-anticoagulation.