Nucleated red blood cells (NRBC) are immature red blood cells. Normally, you can’t find these cells in the bloodstream of adults, so their presence may indicate serious problems with red blood cell production or the bone marrow. Read on to learn more about what the presence of nucleated red blood cells in the circulation can mean for your health.

What are Nucleated RBCs?

As red blood cells mature, they lose their nucleus – a part of the cell where DNA is stored. This enables them to carry more hemoglobin (and therefore more oxygen) and become highly flexible in shape.

Nucleated RBCs (NRBCs, normoblasts) are immature red blood cells (RBCs) that still contain a nucleus. Unlike mature red blood cells, nucleated red blood cells are not deformable, so they are unable to “squeeze” through portholes in the bone marrow and enter the circulation [1, 2, 3].

In healthy adults and older children, NRBCs are usually only found in the bone marrow where they develop and mature. Their presence in the adult blood signifies the disruption of the blood-bone marrow barrier or increased red blood cell production outside the bone marrow [1, 2, 3].

However, NRBCs can commonly be found in the blood of fetuses and newborn babies, especially if they are experiencing growth retardation or a lack of oxygen (hypoxia) [1, 2, 3].

NRBC Blood Test

NRBC test is often requested as a follow-up to abnormal results on a complete blood count (CBC) test in order to check for blood cell abnormalities. In addition, this test may also be of use when a person has signs and symptoms that point to a condition affecting blood cell production or lifespan.

When automatic counters are used for CBC analysis, sometimes NRBCs can be misclassified as white blood cells. This can have negative consequences for patient treatment and outcome. In those cases, NRBCs in the blood film should be counted manually to correct the total white blood cell count [4, 5, 6].

NRBC Normal Range

Nucleated RBCs are quantified by counting the number of NRBCs per 100 white blood cells. WBC counts with even 1 NRBC/100 WBC ’s are to be reported, as only a few NRBCs can have dangerous implications [5].

A normal result should be 0 NRBCs/100 WBCs.

Abnormal Nucleated RBC

The presence of nucleated RBCs in the blood is known as normoblastemia. Mechanisms that can cause normoblastemia are many and are often interrelated [5+].

Causes of Nucleated RBCs in the Blood

1. Low Oxygen

Conditions that reduce the amount of oxygen transported to tissues (hypoxia) cause an increase in red blood cell production, which, in turn, leads to the presence of nucleated RBCs in the blood. These conditions include [5, 1, 7]:

  • Hemorrhage (blood loss)
  • Anemia (hemolytic anemia, iron deficiency anemia, megaloblastic anemia)
  • Thalassemia major, an inherited blood disorder characterized by lower hemoglobin levels and fewer red blood cells in your body than normal.
  • Severe lung disease
  • Congestive heart failure

2. Spleen Dysfunction

Normally, spleen clears nucleated RBCs that escape from the bone marrow. Conditions that affect spleen function can result in the presence of nucleated RBCs in the blood. These include [5, 1]:

  • Sickle cell anemia
  • Essential thrombocytosis, a rare disorder in which your body produces too many blood platelets
  • Hemolytic anemia
  • Malaria
  • Post-splenectomy (surgical removal of the spleen)

3. Bone Marrow Damage

Conditions that damage the bone marrow can change its structure and break down the blood-bone marrow barrier. This leads to the release of nucleated RBCs and immature blood cells into the circulation. These conditions include [5, 8]:

  • Blood cancers (e.g. preleukemia, leukemia, lymphoma, multiple myeloma, myelofibrosis, and myelodysplasia)
  • Neuroblastoma, a form of cancer that develops from immature nerve cells
  • Gaucher disease, a condition characterized by a buildup of certain fatty substances in certain organs, especially your spleen and liver
  • Granuloma (e.g. tuberculosis)
  • Collagen vascular disease (e.g. lupus)
  • Fungal infections
  • Histiocytosis, a group of syndromes characterized by an abnormal increase in the number of certain immune cells called histiocytes (i.e. monocytes, macrophages, and dendritic cells)
  • Sarcoidosis, a disease that causes inflammation in the lungs, skin, eyes, and lymph nodes
  • Osteopetrosis, a rare bone disease that makes bones abnormally dense and prone to break

4. Red Blood Cell Production Outside of the Bone Marrow (Extramedullary hematopoiesis)

Sometimes, bone marrow damage or severe anemia can lead to the production of red blood cells in organs outside of the bone marrow, such as the liver or spleen. Since these organs do not retain immature blood cells as efficiently as the bone marrow, they may release nucleated RBCs into the circulation. Conditions that can cause this include [5, 9]:

  • Myelophthisis, a severe anemia resulting from bone marrow failure
  • Osteopetrosis
  • Myeloid metaplasia, a progressive, chronic disease in which the bone marrow is replaced by fibrous tissue
  • Chronic hemolytic anemia
  • Polycythemia vera, a condition in which the bone marrow makes excess red blood cells
  • Leukemia

5. Other

Finally, other causes of NRBC in the blood include [5, 1, 10]:

  • Uremia, a condition in which urea is found in the blood
  • Sepsis (severe reaction to infection)
  • Liver disease
  • Diabetic ketoacidosis
  • Inflammatory bowel disease
  • Kidney transplant
  • Burns
  • Chemotherapy
  • Lead poisoning
  • Pregnancy

It is unclear why normoblastemia occurs in some of these, but the breakdown of the blood-bone marrow barrier in some of these conditions may play a role [5].

Consequences of Nucleated RBCs

Presence of nucleated RBCs in the blood is associated with poor disease prognosis.

In a study of 383 medical intensive care patients, NRBCs in the blood were associated with increased in-hospital mortality [3].

Similarly, in another study of 284 surgical intensive care patients, patients that were NRBC-positive had an increased risk of death [11].

Ways to Decrease Nucleated RBCs

The primary way to decrease nucleated RBCs is to address any underlying conditions that are causing the presence of nucleated RBCs in the bloodstream.

If you have anemia:

  • Exercise. Moderate physical activity signals your body to increase red blood cell production in order to increase the oxygen supply to your muscles [12]. However, avoid more intense and strenuous forms of exercise, as these can damage and destroy red blood cells. This is one of the reasons that endurance athletes often have anemia [13].
  • Make sure you are not nutrient deficient. Your body should have all the nutrients it needs to produce red blood cells (iron, vitamin B12, folate, copper, and vitamin B6).
  • Reduce or stop your alcohol consumption. It decreases red blood cell production [14].
  • Avoid nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen – they can cause gut injuries and increase blood loss [15].
  • Use antacids or any other drugs that lower stomach acid production sparingly. These decrease iron levels, leading to low red blood cell count [16].
  • Avoid products that contain lead. Although lead is not prevalent in modern homes and buildings, it is possible to still encounter lead paint or manufactured goods. Avoiding lead products will help prevent red blood cell damage [17].
  • Low testosterone levels increase the risk of anemia. To make sure that your testosterone levels are optimal, you should get good quality sleep, lose weight if you are overweight, and exercise regularly [18, 19, 20, 21, 20].
  • Avoid over-using enemas that contain phosphate salts. Your body can absorb these salts, leading to excess phosphate levels in the blood and an increased risk for anemia [22, 23].

These supplements can help with anemia:

Irregular Nucleated RBC Levels?

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