Nucleated red blood cells (NRBCs) are immature red blood cells that still possess a cell nucleus. While these cells are a normal part of development in fetuses and newborn infants, their presence in the peripheral blood of adults is an unusual finding. The appearance of NRBCs in an adult’s bloodstream often suggests an underlying medical condition, indicating the body is under significant stress or experiencing issues with red blood cell production.
The Journey of a Red Blood Cell
The formation of red blood cells, a process called erythropoiesis, primarily occurs in the bone marrow. This process begins with hematopoietic stem cells, which differentiate through several stages to become mature red blood cells. During maturation, these cells gradually synthesize hemoglobin and decrease in size.
Red blood cell maturation involves the extrusion of the nucleus. This process, known as enucleation, occurs just before the cell becomes a reticulocyte. Reticulocytes are immature red blood cells that have lost their nucleus; they are released from the bone marrow into the bloodstream and mature into erythrocytes within one to two days. The absence of a nucleus in mature red blood cells allows them to assume a biconcave shape, increasing their surface-to-volume ratio and flexibility, which aids oxygen transport and navigation.
When Nucleated Red Blood Cells Appear
The presence of nucleated red blood cells in the peripheral blood of adults indicates a disruption in the normal red blood cell production and maturation process. One common reason for their appearance is an increased demand for red blood cell production, often triggered by severe anemia, acute blood loss, or conditions causing rapid red blood cell destruction (hemolysis). This increased demand stimulates the bone marrow to accelerate red blood cell release, sometimes prematurely sending immature, nucleated cells into circulation.
Bone marrow stress or damage can also lead to NRBCs in the bloodstream. This includes conditions like myelofibrosis, where the bone marrow tissue is replaced by fibrous tissue, or infiltration by cancer cells, such as in leukemia or metastatic cancers. Severe infections, certain toxins, or drugs can also disrupt the bone marrow’s normal function, causing the release of these immature cells. Additionally, when red blood cell production occurs outside the bone marrow, known as extramedullary hematopoiesis (e.g., in the liver or spleen), NRBCs may be released because these sites lack the strict regulatory barriers of the bone marrow.
What Their Presence Indicates
Finding nucleated red blood cells in an adult’s blood smear is a marker of underlying physiological stress or disease, rather than a disease itself. Their presence correlates with the severity of conditions such as anemia, chronic low oxygen levels (hypoxemia), or severe infections like sepsis. Even low numbers of NRBCs can prompt further medical investigation to identify the root cause.
NRBCs serve as a prognostic indicator, particularly in critically ill patients. In conditions like sepsis, acute respiratory distress syndrome (ARDS), or severe cardiovascular disease, higher NRBC counts are associated with poorer outcomes and increased mortality. Monitoring changes in NRBC counts also assists healthcare providers in tracking disease progression or assessing a patient’s response to treatment. For instance, a decrease in NRBCs might suggest improvement, while a persistent or rising count could indicate ongoing stress or worsening disease.