A 32-year-old woman with Graves' disease has been on propranolol 40 mg BD and PTU 300 mg TDS for 6 weeks. She presents with fever, sore throat, and a white blood cell count of 1200/μL with severe neutropenia. What is the most appropriate immediate next step in management?

Explanation

## Clinical Recognition of PTU-Induced Agranulocytosis **Key Point:** Agranulocytosis (WBC <1500/μL with severe neutropenia) is a life-threatening idiosyncratic reaction to PTU that requires immediate cessation of the drug. ### Pathophysiology PTU-induced agranulocytosis is an immune-mediated, dose-independent adverse effect that can occur at any time during therapy, even after months of stable use. It is not reversible by dose reduction and represents a medical emergency. ### Management Algorithm ```mermaid flowchart TD A[PTU therapy + fever/sore throat]:::outcome --> B{WBC <1500 with severe neutropenia?}:::decision B -->|Yes| C[STOP PTU immediately]:::urgent C --> D[Switch to methimazole or beta-blocker only]:::action D --> E[Urgent haematology referral]:::action E --> F[Supportive care + infection prophylaxis]:::action B -->|No| G[Continue monitoring]:::action ``` ### Why This Answer Is Correct **High-Yield:** PTU-induced agranulocytosis is an absolute contraindication to continued therapy. The drug must be stopped immediately — dose reduction does NOT prevent progression. 1. **Immediate cessation:** PTU is contraindicated and must be discontinued. 2. **Switch agent:** Methimazole is the alternative thionamide (though it carries a lower but non-zero risk of agranulocytosis). Propranolol alone can provide symptomatic control during the transition. 3. **Urgent haematology evaluation:** Required to assess bone marrow recovery and manage the neutropenia. **Clinical Pearl:** Patients on PTU should be counselled to report fever, sore throat, or mouth ulcers immediately. The incidence of agranulocytosis is ~0.1–0.5% with PTU, making it the most serious adverse effect. ### Monitoring During Recovery - Daily WBC counts until recovery - Infection prophylaxis (e.g., fluconazole for oral candidiasis) - Avoid live vaccines - Consider G-CSF only if WBC remains <500/μL after 48–72 hours of drug cessation [cite:KD Tripathi 8e Ch 41] ## Differential Management Approaches | Scenario | Action | Rationale | |----------|--------|----------| | **Mild leucopenia (WBC 3000–4000)** | Monitor WBC weekly; continue PTU if no symptoms | Reversible; may stabilize | | **Agranulocytosis (WBC <1500) + fever** | STOP PTU; switch to methimazole; haematology referral | Life-threatening; irreversible | | **Agranulocytosis (WBC <500) + sepsis** | Add G-CSF; broad-spectrum antibiotics; ICU support | Severe infection risk | **Warning:** Do NOT attempt to "rescue" PTU therapy by adding G-CSF alone — the drug must be discontinued because the mechanism is immune-mediated, not myelosuppression.