Red blood cells, also known as erythrocytes, are fundamental components of blood, primarily responsible for transporting oxygen from the lungs to the body’s tissues and carrying carbon dioxide back to the lungs for exhalation. These disc-shaped cells are produced within the bone marrow and typically circulate for about 120 days before being removed.
Nucleated Red Blood Cells (NRBCs) are immature forms of red blood cells that still contain a nucleus, unlike mature red blood cells which lose their nucleus during development. While NRBCs are a normal part of red blood cell development within the bone marrow, their presence in the peripheral bloodstream of adults is generally unexpected. When detected, these immature cells can signal important underlying physiological changes, prompting further medical investigation.
The Role of Nucleated Red Blood Cells
Red blood cell development, called erythropoiesis, begins in the bone marrow. Here, precursor cells known as erythroblasts mature through several stages. During this maturation process, these cells gradually accumulate hemoglobin and eventually expel their nucleus before entering the bloodstream as mature red blood cells.
In healthy adults, the bone marrow functions with high efficiency, ensuring that only fully matured, anucleated red blood cells are released into circulation. NRBCs are typically confined to the bone marrow. However, in newborns, especially premature infants, the presence of NRBCs in the peripheral blood is normal and expected. Their red blood cell production system is still developing, and they may also produce fetal hemoglobin, which differs from adult hemoglobin.
Identifying Concerning Levels
Unlike other blood cell counts where a specific numerical threshold indicates concern, even a small number of NRBCs in adult circulation can be significant. The optimal NRBC count in adults is zero.
Laboratory results often report NRBCs as a count per 100 white blood cells (WBCs) or as an absolute value. While some studies suggest that very low counts, such as 0.3/100 WBCs or less, might not always indicate a serious condition, their detection almost always prompts further medical evaluation.
Underlying Reasons for Elevated NRBCs
When NRBCs appear in an adult’s bloodstream, it indicates that the bone marrow is under stress or that its normal regulatory processes are disrupted. One common reason is severe anemia, where the body lacks mature red blood cells. In conditions like hemolytic anemia or severe blood loss, the bone marrow ramps up red blood cell production to compensate, sometimes releasing immature forms prematurely.
Damage or stress to the bone marrow itself can also lead to NRBC release. This can occur in conditions such as myelofibrosis, a disorder where fibrous tissue replaces bone marrow, or in certain types of leukemia where abnormal blood cells proliferate. Severe infections or other systemic illnesses can also stress the bone marrow, causing NRBCs to be released.
Conditions that lead to reduced oxygen delivery to tissues, known as hypoxia, can also stimulate the bone marrow to release NRBCs. Chronic lung diseases, heart failure, or other conditions that impair the body’s ability to oxygenate blood can trigger this response as the body tries to increase oxygen-carrying capacity.
Certain cancers can infiltrate the bone marrow, displacing healthy blood-forming cells and leading to the appearance of NRBCs in the peripheral blood. Other causes include severe sepsis or certain drug effects that interfere with bone marrow function.
Next Steps After a Concerning Result
The detection of nucleated red blood cells in an adult’s blood test is not a diagnosis, but an important indicator. It signals that further investigation is necessary to pinpoint the underlying cause. A doctor will consider this result with a patient’s symptoms, medical history, and other laboratory findings.
Common follow-up actions often include additional blood tests. These may involve a complete blood count (CBC) with differential to assess other blood cell types, a reticulocyte count to measure the rate of new red blood cell production, or iron studies to check for deficiencies. In some cases, a bone marrow biopsy may be necessary to examine the marrow directly. Imaging studies, such as X-rays or CT scans, might also be ordered to look for conditions like tumors or widespread inflammation. Consulting with a healthcare professional is essential for accurate diagnosis and appropriate management.