nRBCs

Nucleated red blood cells (nRBCs) are red blood cell precursors that retain their nucleus. In humans, mature erythrocytes normally lose their nucleus during development in the bone marrow; thus circulating RBCs are enucleated. The presence of nucleated RBCs in peripheral blood is therefore unusual in healthy adults and typically reflects active erythropoiesis or marrow stress.

Development and appearance

Erythropoiesis progresses through several stages, from rubriblasts and prorubricytes to basophilic, polychromatic, and orthochromatic normoblasts, before expelling the nucleus to become reticulocytes and mature red cells. Peripheral nucleated erythroid cells can be seen when marrow output increases rapidly, or when immature cells enter the circulation due to marrow pathology or systemic stress.

Clinical significance

In neonates and newborns, circulating nRBCs can be normal during the early transition of hematopoiesis. In older children and adults, their appearance usually indicates an active marrow response to stress such as severe anemia, hypoxia, hemorrhage, or hemolysis. They can also be produced in conditions that disrupt normal marrow architecture or cause marrow infiltration or extramedullary hematopoiesis, including certain malignancies (e.g., leukemias, myelodysplastic syndromes, myelofibrosis) or following chemotherapy or radiation. Environmental or physiologic factors such as strenuous hypoxia, high altitude adaptation, or severe systemic illness may also contribute.

Detection and interpretation

nRBCs are identified on peripheral blood smears and can be detected by automated hematology analyzers, which may flag them for manual review. The finding should be interpreted alongside reticulocyte count, RBC indices, and clinical context to distinguish benign transitional states from underlying pathology.

Management

Treatment focuses on addressing the underlying cause of marrow stress or infiltration. No specific therapy targets the nRBCs themselves; resolution typically follows stabilization of the hematopoietic environment.