What are the implications of nucleated red blood cells (RBCs) in the peripheral blood?

From the Guidelines

The presence of nucleated red blood cells (NRBCs) in adult peripheral blood is a significant indicator of underlying physiological stress or pathological conditions, and their presence requires prompt clinical correlation and further investigation to determine the cause. When considering the implications of NRBCs, it's essential to understand that their presence in peripheral blood circulation is not normal in healthy adults, as they are typically produced in the bone marrow and extrude their nucleus before entering circulation 1. The presence of NRBCs can indicate accelerated erythropoiesis or disruption of the blood-bone marrow barrier, which can be caused by various conditions such as severe anemia, hemolytic conditions, leukemia, metastatic cancer involving bone marrow, severe infections, and major hemorrhage. Some key points to consider when evaluating NRBCs include:

• NRBCs are normally found in newborns during the first few days of life, but their presence in adult peripheral blood is abnormal.
• Quantification of NRBCs is typically done through peripheral blood smear examination, with results reported as the number of NRBCs per 100 white blood cells.
• The presence of NRBCs requires clinical correlation and further investigation to determine the underlying cause, as they serve as an important diagnostic indicator of serious hematological or systemic disorders requiring prompt medical attention 1. In the context of myelodysplastic syndromes (MDS), the presence of NRBCs may be associated with more aggressive disease, severe anemia, and toxicity related to transfusions themselves, as noted in a study published in the journal Blood 1. Overall, the presence of NRBCs in adult peripheral blood is a significant finding that requires prompt evaluation and investigation to determine the underlying cause and provide appropriate management.

From the Research

Nucleated Red Blood Cells (NRBCs) Overview

• NRBCs are not normally found in the peripheral blood of healthy individuals 2, 3
• The presence of NRBCs in adults indicates a high demand for red blood cell production and can be a sign of underlying pathology 2, 4
• NRBCs can be found in various medical conditions, including anemia, myelofibrosis, thalassemia, and malignancies 2, 5

Clinical Significance of NRBCs

• The presence of NRBCs in critically ill patients is associated with a high mortality rate and poor prognosis 2, 4
• NRBCs can be used as a biomarker to predict mortality and clinical outcome in patients with severe illnesses, such as sepsis, trauma, and acute pancreatitis 4
• A cutoff value of 2.50 NRBCs can indicate a high risk of mortality with a sensitivity of 91% 2

Diagnostic Value of NRBCs

• NRBC count is a cost-effective laboratory test that can be used to diagnose and monitor various medical conditions 4
• Automated hematology analyzers can accurately measure NRBCs, providing a reliable and efficient diagnostic tool 3, 5
• The reference interval for NRBCs has been updated to 0.00-0.10 × 10^6/μL, reducing the number of false positives and unnecessary follow-up care 3

Prognostic Significance of NRBCs

• The presence and concentration of NRBCs can predict poor outcome and increased mortality in patients with hematological diseases and other severe illnesses 2, 4, 6
• NRBCs can appear 1-3 weeks before death, making them a potential early warning sign for patients at high risk 6
• Screening for NRBCs may aid in the early identification of patients at high risk and inform decisions regarding intensive care treatment 6