Red blood cells (RBCs) transport oxygen from your lungs to tissues throughout your body and carry carbon dioxide back. Unlike most other cells, mature mammalian RBCs lack a nucleus, the cell’s control center containing genetic material. Nucleated red blood cells (NRBCs) are immature forms of red blood cells that retain their nucleus. While normally absent in healthy adult peripheral blood, their presence can significantly indicate underlying physiological changes or conditions.
Red Blood Cell Development
The journey of a red blood cell begins in the bone marrow, the spongy tissue found inside certain bones. This process, called erythropoiesis, starts with hematopoietic stem cells, versatile cells that develop into various blood cell types. These stem cells progress through several stages, including proerythroblasts and normoblasts, all of which contain a nucleus.
During the final stages of maturation, before entering the bloodstream, these immature red blood cells undergo enucleation, expelling their nucleus. This allows the mature red blood cell to become a biconcave disc, maximizing its surface area for efficient oxygen exchange and allowing flexibility to navigate narrow blood vessels. After enucleation, the cell briefly exists as a reticulocyte before fully maturing into an erythrocyte.
While mature red blood cells in adults are anucleated, NRBCs are a normal finding in specific contexts. They are commonly present in the circulating blood of fetuses for oxygen transport during development. After birth, these immature cells gradually disappear from the bloodstream of healthy newborns within the first few weeks of life.
When Nucleated Red Blood Cells Appear
The presence of nucleated red blood cells in the peripheral blood of adults or older children is an abnormal finding, signaling bone marrow stress or an increased demand for red blood cell production. They often appear due to an increased need for red blood cells, as seen in severe anemia. For example, in significant blood loss or hemolytic anemia, where red blood cells are rapidly destroyed, the bone marrow may release immature NRBCs prematurely to compensate.
Disorders affecting the bone marrow itself can also lead to the release of NRBCs. Conditions such as myelofibrosis, certain types of leukemia, or other cancers that infiltrate the bone marrow can disrupt its function and structure. This disruption can impair the proper maturation and enucleation of red blood cells, causing immature forms to escape into the bloodstream.
Certain systemic diseases and physiological stressors can trigger the presence of NRBCs. Severe hypoxia, or a lack of oxygen in the body’s tissues, can stimulate the bone marrow to produce red blood cells at an accelerated rate, leading to the release of NRBCs. Severe infections, like sepsis, can also induce hematopoietic stress and result in their circulation.
Clinical Significance
The detection of nucleated red blood cells in an adult’s peripheral blood is clinically significant, indicating an underlying issue that warrants further investigation. While NRBCs are not a specific diagnostic marker for a single disease, their presence often signals hematopoietic stress or bone marrow dysfunction. Healthcare providers use this finding to prompt additional tests, to identify the root cause, which could range from severe anemia to various bone marrow disorders or other serious conditions.
Beyond diagnosis, the count of NRBCs can offer insights into a patient’s prognosis. In critically ill patients, higher circulating NRBCs link to increased illness severity and mortality risk. This makes NRBC counts a valuable biomarker in assessing patient outcomes in conditions such as sepsis, trauma, or acute respiratory distress syndrome.
The monitoring of NRBC counts can also serve as a tool to track disease progression or evaluate a patient’s response to treatment. A decrease in NRBC numbers following intervention might suggest a positive response to therapy and improved bone marrow function. NRBCs are distinct from immature white blood cell precursors, providing unique information about the red blood cell production system.