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Nucleated Red Blood Cells

Nucleated Red Blood Cells

Nucleated red blood cells, if observed, are considered as a red flag for possible underlying diseases. The following HealthHearty article will discuss the significance of red blood cells observed in a peripheral blood film.
Batul Nafisa Baxamusa
Last Updated: Mar 12, 2018
Red blood cells are referred to as erythrocytes in medical terms. These blood cells make up the major chunk of blood that helps carry oxygen and nutrients to each and every cell, tissue, organ, and part of the body through the circulatory system. Under normal circumstances, RBCs appear as flexible, biconcave disks. On further microscopic examination, one observes that these cells lack a cell nucleus and most of the cellular organelles. Thus, when the presence of nucleated red blood cells in their peripheral blood film is detected, one gets alarmed. This is a sign that the person may be suffering from an underlying health problem.
Why is an RBC Count Ordered?

RBC count is always a part of the complete blood count (CBC) test. This test may be ordered as a part of routine physical checkup, or pre-surgical and clinical reasons. Patients with chronic anemia, bleeding problems, and/or hematologic disorders are regularly asked to undergo complete blood count tests. A blood smear test helps the doctor learn more about the blood cell irregularities in their size, shape, and color as well as observe nucleated RBCs.
The Significance

Nucleated RBCs are called normoblasts. These are red blood cells that retain the cell nucleus. These cells are actually precursors for production of normal erythrocytes. These immature RBCs are commonly observed in neonates. Thus, nucleated red blood cells in newborns is not usually a cause for concern. These nucleated RBCs (NRBCs) are present in the peripheral blood of newborns up to 5 days after their birth. However, the appearance of nucleated red blood cells in adults as well as children indicates there may be damage to the bone marrow, stress, or presence of a serious underlying disease. Some of the conditions where one reports presence of NRBCs are as follows:
Asplenia and Hyposplenism
Under normal conditions, it is possible for normoblasts to escape the bone marrow and enter the blood stream. However, they are immediately destroyed by the spleen. If at all one observes NRBCs in the blood, it may suggest hyposplenism. This is a condition where the splenic function has been reduced to some extent. In case splenic function is totally absent, it is called asplenia. This state is usually observed in patients with myeloproliferative disorders as well as sickle-cell disease. Conditions where the bone marrow releases too many NRBCs, it can lead to an overload on the spleen in order to remove their presence from the blood. These conditions that cause excessive release of NRBCs include hypoxia, hemolytic anemia, treatment-induced anemia, malignant neoplasms, collagen vascular diseases, and chemotherapy.
Severe Anemia
When a patient suffers from severe anemia, the oxygen carrying capacity of RBCs is greatly reduced. Thus, hypoxic erythropoietin-induced compensatory erythropoiesis induces production of normoblastemia. Tissue cells suffer from hypoxia which then stimulates the kidneys to produce erythropoietin. This causes intense production of blood cells in the bone marrow. If the process is effective, it will lead to production of reticulocytosis, polychromasia, and NRBCs at times. In case erythropoiesis is ineffective, it causes excessive production of NRBCs that are released prematurely in the peripheral blood.
Hypoxia
When the body or a particular body tissue does not receive adequate supply of oxygen, it leads to hypoxia. Apart from anemia, hypoxia can result due to underlying cardiopulmonary disorders. These cardiopulmonary disorders reduce the capacity of the blood to absorb oxygen. These NBRCs are also present in patients suffering from pulmonary embolism as well as coronary thrombosis.
Conditions Leading to Nucleated Red Blood Cells

There are many other health conditions that may lead to the presence of these NRBCs in the peripheral blood film.
Conditions that Lead to Presence of NRBCs Causative Factors
Bone marrow replacement or invasion
  • Preleukemia
  • Neuroblastoma
  • Osteopetrosis
  • Plasma cell myeloma
  • Severe pulmonary disease
  • Presence of tumor cells
Anemia due to compensatory erythropoiesis
  • Treatment causing anemia
  • Iron deficiency anemia
  • Severe anemia
  • Hemolytic anemia
  • Hemorrhage
  • Thalassemia major
Hyposplenism, asplenia
  • Essential thrombocytosis
  • Hemolytic anemia
  • Malaria
  • Newborn (physiological condition)
  • Sickle cell anemia
  • Splenectomy
Hypoxia
  • Collagen vascular disease
  • Fungal infection
  • Gaucher
  • Granuloma (tuberculosis)
  • Histiocytosis
  • Leukemia
  • Congestive cardiac failure
  • Cyanotic heart disease
  • Lymphoma
Extramedullary hematopoiesis
  • Chronic hemolytic anemia
  • Myeloid metaplasia
  • Osteopetrosis
  • Polycythemia vera
  • Myelophthisis
  • Leukemia
  • Myelofibrosis

As you can see, there are many conditions that lead to nucleated red blood cells in adults. It is important to correct NBRCs as they not only affect the WBC count, but also have serious health consequences in some patients. Thus, a lab report has to mention even the presence of 1 NRBC/100 WBCs. One should keep in mind, the appearance of NRBCs in blood itself does not help in diagnosis of a particular disease. It is just a tool that indicates a situation wherein a serious underlying disease may be present. Thus, helping the patient to get medical intervention as early as possible.
Disclaimer: The information provided in this article is solely for educating the reader. It is not intended to be a substitute for the advice of a medical expert.