To help evaluate the bone marrow's ability to produce red blood cells (RBCs); to help distinguish between various causes of anemia; to help monitor bone marrow response and the return of normal marrow function following chemotherapy, bone marrow transplant, or post-treatment follow-up for iron deficiency anemia, vitamin B12 or folate deficiency anemia, or renal failure
A blood sample obtained by inserting a needle into a vein in your arm or sometimes from a fingerstick or heelstick (infant)
Reticulocytes are newly produced, relatively immature red blood cells (RBCs). A reticulocyte test determines the number and/or percentage of reticulocytes in the blood and is a reflection of recent bone marrow function or activity.
Red blood cells are produced in the bone marrow, where blood-forming (hematopoietic) stem cells differentiate and develop, eventually forming reticulocytes and finally becoming mature RBCs. Reticulocytes are approximately 24% higher in volume in comparison with mature RBCs. Unlike most other cells in the body, mature RBCs have no nucleus, but reticulocytes still have some remnant genetic material (RNA). As reticulocytes mature, they lose the last residual RNA and most are fully developed within one day of being released from the bone marrow into the blood. The reticulocyte count or percentage is a good indicator of the ability of a person's bone marrow to adequately produce red blood cells (erythropoiesis).
RBCs typically survive for about 120 days in circulation, and the bone marrow must continually produce new RBCs to replace those that age and degrade or are lost through bleeding. Normally, a stable number of RBCs is maintained in the blood through continual replacement of degraded or lost RBCs.
A variety of diseases and conditions can affect the production of new RBCs and/or their survival, in addition to those conditions that may result in significant bleeding. These conditions may lead to a rise or drop in the number of RBCs and may affect the reticulocyte count.
Higher than normal percentage of reticulocytes: Acute or chronic bleeding (hemorrhage) or increased RBC destruction (hemolysis) can lead to fewer RBCs in the blood, resulting in anemia. The body compensates for this loss or to treatment of deficiency anemias (such as iron deficiency anemia or pernicious anemia) by increasing the rate of RBC production and by releasing RBCs sooner into the blood, before they become more mature. When this happens, the number and percentage of reticulocytes in the blood increases until a sufficient number of RBCs replaces those that were lost or until the production capacity of the bone marrow is reached.
Lower than normal percentage of reticulocytes: Decreased RBC production may occur when the bone marrow is not functioning normally. This can result from a bone marrow disorder such as aplastic anemia. Diminished production can also be due to other factors, for example, cirrhosis of the liver, kidney disease, radiation or chemotherapy treatments for cancer, a low level of the hormone erythropoietin, or deficiencies in certain nutrients such as iron, vitamin B12, or folate. Decreased production leads to fewer RBCs in circulation, decreased hemoglobin and oxygen-carrying capacity, a lower hematocrit, and a reduced number of reticulocytes as old RBCs are removed from the blood but not fully replaced.
Occasionally, both the reticulocyte count and the RBC count will be increased because of excess RBC production by the bone marrow. This may be due to an increased production of erythropoietin, disorders that cause chronic overproduction of RBCs (polycythemia vera), and cigarette smoking.
Some drugs may increase or decrease reticulocyte counts.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm or sometimes from pricking a finger or the heel of an infant.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
How is it used?
A reticulocyte test is used to determine the number and/or percentage of reticulocytes in the blood to help evaluate conditions that affect red blood cells (RBCs), such as anemia or bone marrow disorders. Reticulocytes are newly produced, relatively immature red blood cells. They form and mature in the bone marrow before being released into the blood.
The reticulocyte test may be used:
- As a follow up to abnormal results on a complete blood count (CBC), RBC count, hemoglobin or hematocrit, to help determine the cause
- To determine if the bone marrow is functioning properly and responding adequately to the body's need for red blood cells
- To help detect and distinguish between different types of anemia
- To monitor response to treatment, such as that for iron-deficiency anemia
- To monitor bone marrow function following treatments such as chemotherapy
- To monitor function following a bone marrow transplant
Most often, a reticulocyte count is performed with an automated instrument (hematology analyzer) and can be done simultaneously with a CBC, which includes an RBC count, hemoglobin and hematocrit. Either an absolute number of reticulocytes and/or a percentage of reticulocytes can be reported. For a percentage, the number of reticulocytes is compared to the total number of RBCs:
Reticulocyte (%) = [Number of Reticulocytes / Number of total Red Blood Cells] X 100
Several other tests may be used in conjunction with a reticulocyte count to further evaluate someone for a condition affecting RBC production. Some examples include:
Sometimes a bone marrow aspiration and biopsy may be done in follow up to abnormal results on initial tests. This procedure is invasive and is not done on everyone. It can, however, provide additional information, if necessary.
When is it ordered?
A reticulocyte count may be ordered when:
- CBC results show a decreased RBC count and/or a decreased hemoglobin and hematocrit
- A healthcare practitioner wants to evaluate bone marrow function
- An individual has signs and symptoms of anemia or chronic bleeding, such as paleness, lack of energy, fatigue, weakness, shortness of breath, and/or blood in the stool
- A person has been diagnosed and is being treated for a condition known to affect RBC production, such as iron deficiency anemia, vitamin B12 or folate deficiency, or kidney disease (which can affect the production of erythropoietin, a hormone produced by the kidneys that stimulates RBC production by the bone marrow)
- An individual is undergoing radiation or chemotherapy
- A person has received a bone marrow transplant
- Occasionally when a person has an increased number of RBCs and elevated hemoglobin and hematocrit, to help determine the degree and rate of overproduction of RBCs
What does the test result mean?
Results must be interpreted carefully and in conjunction with results of other tests, such as a red blood cell (RBC) count, hemoglobin (Hb), hematocrit (Hct), or full CBC. In general, the reticulocyte count (absolute number or percentage) is a reflection of recent bone marrow activity. Results may indicate whether a disease or condition is present that is generating an increased demand for new RBCs and whether the bone marrow is able to respond to the extra requirement. Occasionally, results may indicate overproduction of RBCs.
When anemia is present (i.e., low RBCs, low hemoglobin, low hematocrit) and the bone marrow is responding appropriately to the demand for increased numbers of RBCs, then the bone marrow will produce more and allow for the early release of more immature RBCs, increasing the number of reticulocytes in the blood.
A high reticulocyte count with low RBCs, low hemoglobin, and low hematocrit (anemia) may indicate conditions such as:
- Bleeding: If an individual bleeds (hemorrhage), then the number of reticulocytes will rise a few days later in an attempt to compensate for the red cell loss. If someone has chronic blood loss, then the number of reticulocytes will stay at an increased level as the marrow tries to keep up with the demand for new RBCs (although it may not be high if the blood loss leads to iron deficiency).
- Hemolytic anemia: In this condition, anemia is caused by increased destruction of RBCs. The bone marrow increases RBC production to compensate, resulting in a high reticulocyte count.
- Hemolytic disease of the newborn: This condition causes increased RBC destruction, similar to hemolytic anemia described above.
A low reticulocyte count with low RBCs, low hemoglobin, and low hematocrit (anemia) may be seen, for example, with:
- Iron deficiency anemia
- Pernicious anemia or folic acid deficiency
- Aplastic anemia
- Radiation therapy
- Bone marrow failure caused by infection or cancer
- Severe kidney disease; this may cause a low level of erythropoietin.
- Endocrine disease
When an individual has anemia, the percent of reticulocytes present in the blood may appear high compared to the overall number of RBCs. In order to get a more accurate assessment of bone marrow function, a calculation called a corrected reticulocyte count or reticulocyte index (RI) may be reported. The RI is calculated by comparing the person's hematocrit with a normal hematocrit value. Other calculations that may also be reported include the reticulocyte production index (RPI) and an immature reticulocyte fraction (IRF). The IRF was previously referred to as the reticulocyte maturity index; however, IRF is now the most common term used to quantify the younger fraction of reticulocytes. (For more on these, see the Common Questions section.)
The reticulocyte test gives an indication of the presence of a disease or condition but is not directly diagnostic of any one particular disease. It is a sign that further investigation may be necessary and a tool that can be used to monitor the effectiveness of therapy.
If reticulocyte numbers rise following chemotherapy, a bone marrow transplant, or treatment of an iron or vitamin B12 or folate deficiency, then bone marrow RBC production is beginning to recover.
When an individual does not have anemia, or has a high RBC count (polycythemia), a high reticulocyte count may indicate an overproduction of RBCs. Some conditions that may cause this include:
- Polycythemia vera
- Tumor that produces excess erythropoietin
Is there anything else I should know?
People who move to higher altitudes may have high reticulocyte counts for a while as their body adapts to the lower oxygen content of their new location. Smokers also may demonstrate an increased number of RBCs and reticulocytes.
Reticulocyte counts may be high during pregnancy. Newborns have a higher percentage of reticulocytes, but the number drops to near adult levels within a few weeks of birth.
Traditionally, reticulocyte counts have been done manually by looking at a specially stained slide under the microscope and counting the number of reticulocytes in a number of fields of view. Although it is used occasionally, the manual method has been replaced by automated methods that allow for a greater number of cells to be counted, thus enhancing the accuracy of reticulocyte counts. The automated method is considered to be more accurate in identifying reticulocytes.
What is a corrected reticulocyte count (CRC), also called reticulocyte index (RI)?
When an individual has anemia (the number of red blood cells (RBCs), hemoglobin and hematocrit are low), the percentage of reticulocytes may appear high compared to the overall number of RBCs. This is in part due to the immature cells' early release from the bone marrow into circulation and the longer time they spend maturing in the blood (from the normal 1 day to 3 or 4 days). In order to get a more accurate assessment of bone marrow function, the reticulocyte percentage (%) is often corrected with a calculation called a corrected reticulocyte count (CRC) or a reticulocyte index (RI). This calculation compares the person's hematocrit with a normal hematocrit value:
Reticulocyte Index = Reticulocyte count (%) X [Measured hematocrit / Normal hematocrit]
What is a reticulocyte production index (RPI)?
In addition to the RI, a calculation called the reticulocyte production index (RPI) is sometimes calculated to correct for the degree of reticulocyte immaturity, reflecting how early the reticulocytes were released from the bone marrow and how long it will take them to mature in the bloodstream. The RPI and maturation time vary with the hematocrit.
Reticulocyte Production Index = (Reticulocyte Index) X (1/maturation time)
What is immature reticulocyte fraction (IRF)?
The immature reticulocyte fraction (IRF) is calculated as a ratio of immature reticulocytes to the total number of reticulocytes. It is reported by an automated blood analyzer when a reticulocyte count test is performed. In certain conditions, IRF is a better indicator of bone marrow response than a total reticulocyte count.
My complete blood count (CBC) report includes a result for reticulocyte hemoglobin. What is it?
The hemoglobin inside of reticulocytes can be measured and reported as either a mean reticulocyte hemoglobin content (CHr) or a reticulocyte hemoglobin equivalent (Ret-He), depending upon the test method used. This test result would be one of the values reported when blood is evaluated using an automated hematology analyzer.
Reticulocytes are "young" red blood cells that are released by the bone marrow before they become fully mature. The amount of hemoglobin inside of reticulocytes can help determine if there has been enough iron available, to be incorporated into hemoglobin production and then into red blood cell production in the bone marrow, within the past few days. This makes the test useful in identifying functional iron deficiency in certain clinical conditions and in assessing iron deficiency anemia in children.
Can the reticulocyte count be done on the same tube of blood as the RBC count or CBC?
Yes. If anemia is detected during a routine blood test, the health practitioner may order additional testing (including a reticulocyte count) on the same tube of blood if it can be done on the same day.
Will a blood transfusion affect reticulocyte results?
How else might my doctor evaluate the cell production in my bone marrow?
In some cases, a procedure called a bone marrow aspiration may be performed to obtain a sample of marrow to evaluate under the microscope. Sometimes this is the best way for a healthcare provider to determine how well the bone marrow is functioning.
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Tests: Red Blood Cell Count; Hemoglobin; Hematocrit; Complete Blood Count; Blood Smear; Erythropoietin; Vitamin B12 and Folate; Haptoglobin; G6PD; Iron Tests; Bone Marrow Aspiration and Biopsy
Conditions: Anemia, Bone Marrow Disorders, Myeloproliferative Neoplasms
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