Nucleated Red Blood Cells

Nucleated RBC counts are frequently used for newborns and young infants. Premature infants can have NRBC counts as high as100 NRBC per 100 WBC. The presence of circulating NRBCs, outside of the neonatal period, generally indicates either increased red blood cell production or bone marrow infiltration. Severe hypoxia, acute hemolytic anemia, thalassemia increase erythropoietic activity and red cell production. NRBCs can also be released into the circulation when the bone marrow is infiltrated by malignant cells, fibrosis, and granulomas.

The most common circulating NRBC is at the orthochromic stage of differentiation, although the term NRBC is used for all normoblasts regardless of the stage of maturation. NRBC have a size and nucleus similar to lymphocytes. As a result many hematology analyzers misclassify NRBC and produce an inaccurate total white blood cell count and lymphocyte count. Patients may undergo additional testing and possibly unnecessary treatment if NRBC are misclassified as lymphocytes. 

Modern hematology instruments automatically correct the WBC count when NRBCs are detected. However, even the most sophisticated instruments will, at times, misidentify these cells necessitating a manual correction of the WBC count. Therefore, review of the peripheral blood smear for confirmation of the number of circulating NRBCs is important when NRBCs are flagged as being detected. 

The formula for correcting WBC counts when NRBCs are present is as follows:

Corrected WBC (cells/uL) = Uncorrected WBC x 100/(NRBC+100)

If the instrument has already attempted to correct the WBC, it is necessary to retrieve the uncorrected WBC count from the instrument for the calculation.

References

Pikora K, et al, Diagnostic Value and Prognostic Significance of Nucleated Red Blood Cells (NRBCs) in Selected Medical Conditions. Cells. 2023 Jul 9;12(14):1817.

Doig K, Thompson LA, A Methodical Approach to Interpreting the White Blood Cell Parameters of the Complete Blood Count, Amer Soc Clin Lab Sci,2017;30(3):186-193.