What is the most likely reason for the elevated Hemoglobin F (Hb F) level in a patient with sickle cell disease (SCD)?

Elevated Hemoglobin F in Sickle Cell Disease: Hydroxycarbamide (Hydroxyurea) Therapy

The elevated Hemoglobin F (HbF) level of 11.4% in this 13-year-old female with sickle cell disease is most likely due to hydroxycarbamide (hydroxyurea) therapy, which is the standard treatment for reducing complications and mortality in sickle cell disease. 1

Clinical Presentation Analysis

The patient presents with:

• 13-year-old female with known hemoglobinopathy
• Acute pain in joints and abdomen (suggestive of vaso-occlusive crisis)
• Severe anemia (Hb 7.2 g/dL)
• Elevated HbF (11.4%)
• Hemoglobin S (85%)

These findings are consistent with sickle cell anemia (HbSS) being treated with hydroxycarbamide.

Mechanism of Hydroxycarbamide (Hydroxyurea) in SCD

Hydroxycarbamide works through several mechanisms:

1. Increases HbF production: Hydroxycarbamide raises HbF levels, typically to >8%, which reduces HbS polymerization 1
2. Reduces sickling: HbF interferes with the polymerization of HbS molecules, offering protection against sickling 1
3. Improves clinical phenotype: Patients with higher HbF levels (>8%) tend to have milder disease with fewer symptoms 1

Evidence Supporting Hydroxycarbamide as the Cause

The patient's HbF level of 11.4% is significantly elevated above the typical range for untreated sickle cell anemia (5-15%) 1. This elevation is characteristic of hydroxycarbamide therapy, which is now recommended as standard therapy for many patients with sickle cell disease 1.

Key supporting evidence:

• Hydroxycarbamide raises HbF levels and is now recommended as standard therapy for many patients 1
• Patients with high HbF levels (>8%) tend to have milder disease phenotype 1
• The combination of 85% HbS and 11.4% HbF is consistent with HbSS on hydroxycarbamide therapy 1

Laboratory Findings Interpretation

The patient's CBC shows:

• Severe anemia (Hb 7.2 g/dL)
• Elevated RDW (22.4%)
• Thrombocytosis (682 × 10³ cells/µL)
• Normal MCV (89.8 fL)

These findings are consistent with sickle cell anemia with compensatory bone marrow response. The normal MCV (rather than microcytosis) further supports hydroxycarbamide therapy, as this medication typically increases MCV 2.

Alternative Explanations (Less Likely)

1. Combination therapy with erythropoietin: Some patients receive combination therapy with hydroxycarbamide and erythropoietin, which can further increase HbF levels 1, 3. However, this is less common and typically reserved for patients with renal insufficiency.

2. Hereditary persistence of fetal hemoglobin: This is unlikely given the high percentage of HbS (85%) and clinical presentation consistent with sickle cell disease.

Clinical Implications

The elevated HbF level of 11.4% indicates:

1. The patient is likely responding well to hydroxycarbamide therapy
2. This elevated HbF provides some protection against sickling complications
3. Despite this protection, the patient still experienced a vaso-occlusive crisis requiring emergency care

Final Diagnosis

The patient has sickle cell anemia (HbSS) being treated with hydroxycarbamide (hydroxyurea), which has successfully increased her HbF levels to 11.4%. The elevated HbF is a therapeutic effect of hydroxycarbamide, which is recommended as standard therapy for reducing mortality and complications in sickle cell disease 1.

Management Considerations

• Continue hydroxycarbamide therapy as it appears to be effective in raising HbF
• Monitor for potential side effects of hydroxycarbamide, particularly neutropenia 1
• Consider increasing the dose if clinically indicated, as higher doses may further increase HbF levels 2
• Ensure adequate hydration and pain management during acute crises