What does an NRBC (Nucleated Red Blood Cells) level indicate?

Understanding NRBC Level of 1 in Laboratory Testing

The presence of nucleated red blood cells (NRBCs) at a level of 1 per 100 white blood cells is abnormal in adults and indicates underlying pathology that requires further investigation, as NRBCs should not normally be present in peripheral blood of healthy adults.

What are NRBCs?

Nucleated red blood cells (NRBCs) are immature erythrocyte precursors that:

• Normally reside in the bone marrow as part of erythropoiesis
• Should not be present in the peripheral blood of healthy adults
• May be found in the blood of fetuses and neonates 1

Clinical Significance of NRBCs in Adults

The presence of NRBCs in peripheral blood of adults is associated with:

1. Hematological disorders:

   • Ineffective erythropoiesis
   • Stress erythropoiesis
   • Primary alterations of hematopoiesis 2

2. Critical illness:

   • High mortality in intensive care patients
   • Sepsis, trauma, ARDS, acute pancreatitis
   • Severe cardiovascular disease 1, 3

3. Prognostic significance:

   • Detection of NRBCs is highly predictive of mortality in critically ill patients
   • Odds ratio for mortality increases by 1.01 for each increase in NRBC concentration of 1×10^6/L 3
   • NRBCs are detected approximately 13 days (median 8 days) before death in critical patients 3

Diagnostic Approach for Patients with NRBCs

When NRBCs are detected at a level of 1 per 100 WBCs, the following diagnostic approach is recommended:

1. Complete Blood Count Analysis

• Evaluate hemoglobin and hematocrit levels to assess for anemia
• Check MCV to classify anemia as microcytic, normocytic, or macrocytic 4
• Examine RDW (red cell distribution width) to help differentiate causes of anemia 4
• Review reticulocyte count to assess bone marrow response 4

2. Peripheral Blood Smear

• Confirm the presence of NRBCs
• Assess for other morphological abnormalities
• Look for signs of hemolysis or other RBC abnormalities 4

3. Iron Studies

• Serum ferritin (most specific test for iron deficiency)
• Transferrin saturation
• Serum iron and total iron binding capacity 5

4. Additional Testing Based on Clinical Suspicion

• Vitamin B12 and folate levels if macrocytic anemia is present
• Hemolysis workup (haptoglobin, LDH, indirect bilirubin)
• Bone marrow examination if myelodysplastic syndrome or other bone marrow disorders are suspected 4

Clinical Implications and Management

The management approach depends on the underlying cause:

1. For hematological disorders:

   • Treat underlying condition (iron deficiency, B12/folate deficiency)
   • Consider referral to hematology if myelodysplastic syndrome or other serious bone marrow disorders are suspected 4

2. For critically ill patients:

   • More intensive monitoring may be warranted
   • Consider the presence of NRBCs as a poor prognostic indicator 3
   • Address underlying critical illness

3. For oncology patients:

   • NRBCs may be present during chemotherapy and absent at remission
   • Monitor during treatment 2

Important Considerations and Pitfalls

• Laboratory correction: NRBCs can falsely elevate white blood cell counts on automated analyzers, requiring manual correction 6
• Persistence: Persistent NRBCs beyond day 3-4 are particularly concerning and associated with higher mortality 7
• Quantification: The magnitude of NRBC elevation correlates with severity of illness and mortality risk 3
• Monitoring: Serial measurements may provide more valuable information than a single measurement 7

Conclusion

An NRBC level of 1 per 100 WBCs is abnormal in adults and warrants further investigation. While this finding alone is not diagnostic of a specific condition, it serves as an important marker of underlying pathology and may have significant prognostic implications, particularly in critically ill patients.