What is the management approach for a 15-year-old female with nucleated red blood cells (NRBCs) present in her peripheral blood?

Management of a 15-Year-Old Female with NRBC Count of 1

The presence of a single nucleated red blood cell (NRBC) in a 15-year-old female is likely clinically insignificant and requires no specific intervention, but warrants a basic workup to rule out underlying pathology.

Understanding NRBCs

Nucleated red blood cells (NRBCs) are immature erythrocyte precursors that normally reside in the bone marrow and are rarely present in the peripheral blood of healthy individuals beyond the neonatal period 1. Their presence in peripheral blood may indicate:

• Bone marrow stress
• Hypoxemia
• Hematologic disorders
• Severe systemic illness

Clinical Significance of NRBC Count of 1

A single NRBC in the peripheral blood of a 15-year-old female should be interpreted in context:

• Recent research indicates that the upper limit of normal for NRBCs can be as high as 0.10 × 10^6/μL 2
• An isolated finding of a single NRBC without other abnormalities may not be clinically significant
• The traditional view that any NRBC presence is pathological has been challenged by modern automated hematology analyzers that can detect very low levels 2

Recommended Evaluation

Initial Assessment:

• Complete blood count (CBC) with differential to evaluate for anemia, thrombocytopenia, or leukocytosis/leukopenia
• Peripheral blood smear review to confirm NRBC finding and assess for other morphologic abnormalities
• Basic metabolic panel to assess renal function

If CBC is Otherwise Normal:

• Repeat CBC in 4-8 weeks to determine if NRBCs persist
• No further workup needed if the repeat CBC shows no NRBCs and other parameters remain normal

If CBC Shows Abnormalities or NRBCs Persist:

1. Evaluate for potential causes:

   • Iron studies (serum ferritin, transferrin saturation) to assess for iron deficiency 3
   • Hemolysis workup (reticulocyte count, LDH, haptoglobin)
   • Consider hemoglobinopathy evaluation if MCV is low 3

2. If significant cytopenias are present:

   • Consider bone marrow examination, especially if there are concerns for myelodysplastic syndrome (MDS) or other bone marrow disorders 4
   • Flow cytometry and cytogenetic testing may be indicated 4

When to Consider More Serious Pathology

More extensive evaluation is warranted if:

• Multiple NRBCs are present (>5-10/100 WBCs)
• NRBCs persist on repeat testing
• Patient has symptoms such as fatigue, pallor, bleeding, or bruising
• Other CBC abnormalities are present
• Patient has a history of malignancy or known hematologic disorder

Follow-up Recommendations

• If initial workup is normal: Reassurance and repeat CBC in 3-6 months
• If mild abnormalities: More frequent monitoring (every 1-3 months) based on clinical context
• If significant abnormalities: Referral to hematology for further evaluation

Important Considerations

• The presence of NRBCs in critically ill patients has been associated with increased mortality, but this applies primarily to hospitalized adults with severe illness, not to otherwise healthy adolescents 5
• Modern automated analyzers can detect very low levels of NRBCs that may have been missed by traditional manual methods 6
• Avoid unnecessary extensive workups for isolated, low-level NRBC findings in the absence of other abnormalities

By following this approach, clinicians can appropriately evaluate the significance of a single NRBC in a 15-year-old female while avoiding unnecessary testing or concern.