A 5-year-old boy with β-thalassemia intermedia presents with extramedullary hematopoiesis causing splenomegaly and hepatomegaly. His hemoglobin is 7.5 g/dL and he is transfusion-dependent. Which agent is the drug of choice to reduce transfusion requirements by increasing fetal hemoglobin (HbF) production?

Explanation

## HbF Induction in Thalassemia Intermedia **Key Point:** Hydroxyurea is the first-line pharmacological agent for increasing fetal hemoglobin (HbF) production in thalassemia intermedia and major, thereby reducing transfusion dependence. ### Mechanism of Hydroxyurea **High-Yield:** Hydroxyurea induces HbF production by: 1. Reactivating γ-globin gene expression (silenced after birth) 2. Increasing erythroid progenitor proliferation 3. Reducing sickling and hemolysis (in sickle cell disease) 4. Improving hemoglobin levels by 1–3 g/dL in responders ### Efficacy in Thalassemia | Outcome | Hydroxyurea | Splenectomy | Folic Acid | EPO | |---------|-------------|-------------|-----------|-----| | **HbF induction** | Yes (30–50% increase) | No | No | No | | **Transfusion reduction** | Yes (50–80% of patients) | Modest | No | Minimal | | **Mechanism** | γ-globin reactivation | Reduces splenic sequestration | Supports RBC production | Stimulates RBC production | | **Onset** | 4–12 weeks | Immediate (post-op) | Weeks | Days–weeks | | **First-line status** | Yes | Adjunctive | Supportive | Adjunctive | **Clinical Pearl:** Hydroxyurea is particularly effective in β-thalassemia intermedia, where HbF induction can reduce or eliminate transfusion requirements. Responders show HbF levels rising from <5% to 15–30%, significantly improving oxygen-carrying capacity. **Mnemonic:** **HYDROXYUREA = Helps Yield Reactivated Oxygen-carrying Hemoglobin (fetal), eXcels in Young patients, Useful for Reducing transfusion Exigency in Anemia** ### Monitoring During Hydroxyurea Therapy - CBC (baseline, 2 weeks, then monthly) - Renal function and LFTs (monthly) - HbF level (at 4–12 weeks to assess response) - Bone marrow reserve (assess for myelosuppression) **Warning:** Hydroxyurea is teratogenic (Pregnancy Category D) and contraindicated in pregnant women. Counsel on contraception in reproductive-age patients. Myelosuppression is dose-limiting; monitor CBC closely.