Developing erythroblasts are nucleated in the the bone marrow. In normal situations the nucleus is excluded before the immature red cell (reticulocyte) is released into circulation. It is common to find circulating nucleated red blood cells (NRBCs)in neonates but these are not found after a few days.
NRBCs are found in increased numbers in premature infants and those with fetal hypoxia or asphyxia. They are also found in haemolytic disease of the newborn, originating from extramedullary sites in the liver and spleen. In adults, circulating NRBCs can be found when the marrow is stressed such as in acute hypoxia, blood loss, severe infection or haemolytic anaemia. They can also be found when there is marrow infiltration such as in carcinoma or leukaemia/MDS.
In the laboratory, Sysmex analysers can differentiate NRBCs from white blood cells by firstly lysing the red blood cells and then staining the white and nucleated red cell nuclei with fluorescent dye. These two populations can then be separated using Laser Light Forward Scatter and Fluorescence measurements in Sysmex XE analysers and Forward Scattered Light and Side Fluorescent Light measurements in Sysmex XN analysers.
Alternatively, if NRBCs are present in the blood film, they can be either counted by CellaVision or using the microscope and then the white count corrected.
Corrected WBC = Uncorrected WBC x (100/[NRBCs per 100 white cells + 100])