If a patient on hydroxyurea 15 mg/kg/day with normal baseline counts develops anemia (hemoglobin <10 g/dL) during dose escalation, should I hold the medication?

Yes, Hold Hydroxyurea Immediately When Hemoglobin Falls Below 10 g/dL

You must discontinue hydroxyurea immediately when hemoglobin drops below 10 g/dL during dose escalation, as this meets mandatory discontinuation criteria established by NCCN and European LeukemiaNet guidelines for hydroxyurea intolerance. 1

Why This Threshold Matters

• Hemoglobin <10 g/dL is an absolute discontinuation criterion for hydroxyurea therapy at any dose, regardless of whether you're treating myeloproliferative neoplasms or sickle cell disease 1, 2
• The FDA label explicitly states that bone marrow suppression manifests first as leukopenia, but when anemia occurs, it signals significant myelosuppression requiring immediate intervention 2
• This threshold represents a safety boundary where the risks of continued therapy outweigh potential benefits 1

Immediate Management Steps

When Hgb drops below 10 g/dL:

• Stop hydroxyurea completely until hemoglobin recovers 1, 2
• Monitor complete blood counts weekly during the recovery period 1
• Check for other causes of anemia: review peripheral smear, assess iron/folate/B12 status, evaluate for occult blood loss, and consider hemolysis markers (LDH, haptoglobin, reticulocyte count, bilirubin, Coombs testing) 3, 2
• Rule out hydroxyurea-induced hemolytic anemia if patient develops acute jaundice or hematuria with worsening anemia 2

Additional Cytopenias Requiring Discontinuation

Also hold hydroxyurea if:

• Absolute neutrophil count <1.0 × 10⁹/L 1, 4
• Platelet count <100 × 10⁹/L (for polycythemia vera) 1, 4
• Development of leg ulcers or mucocutaneous toxicity 1

Context for Dose Escalation in Sickle Cell Disease

• The standard dose escalation protocol for sickle cell disease starts at 15 mg/kg/day with increases to maximum tolerated dose (typically 20-35 mg/kg/day) 5, 6
• However, even at the initial 15 mg/kg/day dose, if hemoglobin falls below 10 g/dL, you must stop 1
• Studies show that 15 mg/kg/day produces significant clinical benefit with minimal side effects, and some patients may not require escalation to higher doses 5
• Recovery from myelosuppression is usually rapid once hydroxyurea is interrupted 2

When to Consider Restarting

• Once hemoglobin recovers above 10 g/dL and other counts normalize, you may cautiously restart at a reduced dose (typically 25-50% lower than the dose that caused suppression) 3
• If anemia recurs at lower doses, this patient demonstrates hydroxyurea intolerance and requires alternative therapy 1

Common Pitfall to Avoid

Do not continue hydroxyurea hoping the anemia will self-correct or that increasing fetal hemoglobin will eventually improve total hemoglobin. While hydroxyurea does increase hemoglobin in most sickle cell patients over time 7, 5, a drop below 10 g/dL during dose escalation indicates excessive marrow suppression that requires immediate cessation 1, 2.