Nucleated red blood cells (NRBC) are immature red blood cells. Their presence in the bloodstream may indicate serious problems with RBC production or the bone marrow. Read on to learn more details about the presence of NRBC in your blood and what you can do about it.

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 the mature ones, nucleated red blood cells are unable to “squeeze” through portholes in the bone marrow and enter the circulation [1, 2, 3].

In healthy adults and children, NRBCs are usually only found in the bone marrow where they develop and mature. Their presence in the 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 are common in the blood of fetuses and newborn babies, especially if they are experiencing growth retardation or a lack of oxygen [1, 2, 3].

Nucleated red blood cells (NRBCs) are immature RBCs. In adults, their presence in the blood indicates a problem with bone marrow or RBC production.

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. It may also be of use when a person has signs and symptoms of 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 [4, 5, 6].

Your doctor may order an NRBC test if CBC test results indicate blood cell issues. To avoid mistakes, NRBC count should be confirmed manually.

Normal NRBC Levels

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

A normal result is 0 NRBCs/100 WBCs.

Abnormal Nucleated RBC Levels

The presence of nucleated RBCs in the blood is known as normoblastemia—a complex condition with many possible causes [5].

Causes

1. Low Oxygen

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

  • Hemorrhage (blood loss)
  • Anemia (hemolytic anemia, iron deficiency anemia, megaloblastic anemia)
  • Thalassemia major
  • Severe lung disease
  • Congestive heart failure
The presence of NRBCs in the blood can occur due to the lack of oxygen supply caused by blood loss or different health conditions.

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 with the overproduction of platelets)
  • Hemolytic anemia
  • Malaria
  • Splenectomy (surgical removal of the spleen)
Conditions that affect the spleen can prevent the removal of NRBCs from the blood.

3. Bone Marrow Damage

Conditions that damage the bone marrow can break down the blood-bone marrow barrier and release NRBCs and into the circulation. These conditions include [5, 8]:

  • Blood cancers (e.g. preleukemia, leukemia, lymphoma, multiple myeloma, myelofibrosis, and myelodysplasia)
  • Neuroblastoma (cancer of immature nerve cells)
  • Gaucher disease (the buildup of fats in certain organs, especially the spleen and liver)
  • Tuberculosis
  • Collagen vascular disease (e.g. lupus)
  • Fungal infections
  • Sarcoidosis (inflammation in the lungs, skin, eyes, and lymph nodes)

4. RBC Production Outside of the Bone Marrow (Extramedullary Hematopoiesis)

Bone marrow damage or severe anemia can lead to the production of red blood cells in other organs such as the liver or spleen, which may release NRBCs into the circulation. Such conditions include [5, 9]:

  • Myelophthisis (severe anemia resulting from bone marrow failure)
  • Myeloid metaplasia (progressive bone marrow scarring)
  • Chronic hemolytic anemia
  • Polycythemia vera (excess RBC production)
  • Leukemia

5. Other

Other causes of NRBC in the blood (normoblastemia) include [5, 1, 10]:

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

Consequences

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

In two studies of over 600 intensive care patients, NRBCs in the blood were associated with increased mortality [3, 11].

Ways to Decrease Nucleated RBCs

The primary way to decrease nucleated RBCs is to address any underlying conditions.

If you have anemia:

1. Exercise: Moderate physical activity signals your body to increase red blood cell production in order to increase the oxygen supply to your muscles [12].

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].

2. 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).

3. Reduce or stop your alcohol consumption. It decreases red blood cell production [14].

4. Avoid NSAIDs such as ibuprofen — they can cause gut injuries and increase blood loss [15].

5. Be cautious with antacids and other drugs that suppress stomach acid. These decrease iron levels, leading to low RBCs [16].

6. Avoid products that contain lead, such as lead paints; it will help prevent red blood cell damage [17].

7. Boost testosterone levels by getting good quality sleep, losing weight if you are overweight, and exercising regularly [18, 19, 20, 21, 20].

To reduce NRBCs, address the underlying cause such as anemia by exercising, getting adequate nutrition, increasing testosterone, and avoiding NSAIDs.

These supplements can help with anemia:

Irregular Nucleated RBC Levels?

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Takeaway

Nucleated red blood cells (NRBCs) are immature red blood cells produced in the bone marrow. In adults, their presence in the blood indicates a problem with bone marrow integrity or RBC production.

Your doctor may order an NRBC test if other blood test results (such as CBC) indicate blood cell issues. A normal result is 0 NRBCs/100 WBCs or a complete absence of NRBCs in the blood.

Possible causes of NRBCs in the blood include anemia, low oxygen, spleen dysfunction, and bone marrow damage and disorders. You can reduce NRBCs by addressing the underlying cause.

If you have anemia, make sure to exercise regularly, get adequate nutrition and, increase testosterone. Avoid NSAIDs and drugs that suppress stomach acid and consider taking folate, iron, selenium, spirulina, and vitamins B12, D, E.

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