What Is a Reticulocyte Count and Index?

The reticulocyte count is an extremely valuable blood test for determining the health of the bone marrow and can play a key role in the initial workup of anemia. Reticulocytes are "adolescent" red blood cells that have just been released from the bone marrow into the circulation and are present in the blood for only around one day before maturing into "adult" red blood cells.

The bone marrow is continually replenishing red blood cells so that roughly 1% of the red blood cells are reticulocytes at any time. A high reticulocyte count may be seen with bleeding or breakdown of red blood cells, as the bone marrow releases more reticulocytes to compensate for the loss. In contrast, a low reticulocyte count can mean that the bone marrow isn't functioning properly or that a deficiency (such as iron) is interfering with the production of red blood cells.

The reticulocyte count (known as absolute reticulocyte count) can be misleading when anemia is present, and one or two calculations (the corrected reticulocyte count and reticulocyte production index) may be needed to make sure the count accurately describes what is happening in the bone marrow.

Purpose of Test

Reticulocytes are immature (but without a nucleus) red blood cells that are named for their granular or "reticulated" appearance under the microscope. There are a number of reasons why a healthcare provider may order a reticulocyte count. Some of these include:

• to evaluate abnormal findings on a complete blood count (CBC) such as a high or low red blood cell count, white blood cell count, or platelet count. The count can also be helpful if levels of all types of blood cells are low (pancytopenia)
• to evaluate low hemoglobin or hematocrit (anemia)
• to assess bone marrow function
• to monitor treatment response after therapy is started for some types of anemia, such as that due to iron deficiency or vitamin B12 deficiency
• to assess bone marrow function after chemotherapy
• to assess the function of the bone marrow after a bone marrow transplant

Reticulocyte Count Measurement and Meaning

Red blood cells normally live in the bloodstream for around 120 days but are continuously being replenished from the bone marrow.

The reticulocyte count is a measure of the immature red blood cells (reticulocytes or "adolescent" red blood cells) recently released from the bone marrow into the circulation and is ordinarily around 1% in people who have a normal red blood cell count.

Absolute Reticulocyte Count

The reticulocyte count is calculated by dividing the number of reticulocytes by the total number of red blood cells:

• Reticulocyte Count (Percent) = Number of Reticulocytes / Number of Red Blood Cells

While a normal reticulocyte count in someone who is not anemic is around one, the reticulocyte count is expected to increase with anemia to different degrees. It's thought that the bone marrow is capable of producing up to eight times as many red cells when necessary.

If the reticulocyte does not increase, it suggests that there is a problem in the bone marrow or a deficiency of substances needed to make red blood cells.

Corrected Reticulocyte Count and Reticulocyte Production Index

If a person has anemia, the absolute reticulocyte count can be misleading, as it can be difficult to know whether or not the reticulocyte count has increased to the degree expected with the severity of a case of anemia. Calculations to determine the corrected reticulocyte count and sometimes the reticulocyte production index can solve this problem.

Testing

The reticulocyte is usually tested using an automated analyzer, but the test may be done manually as well or when results obtained are in question.

Limitations

There are a few limitations with the reticulocyte count that could lead to less accurate or inaccurate results. If a person has had a recent blood transfusion, the count will reflect both the person's blood and the donated blood.

Lab errors, such as inaccurate counting (when done manually), procedural problems in drawing the blood, inadequate refrigeration of the sample, or contamination sometimes occur.

False positives (a falsely high reticulocyte count) can occur when cells with other red blood cell inclusions are mistakenly thought to be reticulocytes. Examples include Howell-Jolly bodies, Heinz bodies, siderocytes, and more.

Complementary Tests

A reticulocyte count is usually ordered along with (or after) a complete blood count (CBC). The complete blood count (CBC) includes the total number of the different types of blood cells present.

• Red blood cell count (RBCs)
• White blood cells (WBCs)
• Platelets

The red blood cell indices included in the CBC describe characteristics of the red blood cells and are very helpful in the diagnosis of anemia when combined with the reticulocyte count.

• Mean corpuscular volume (MCV) is a measure of the average size of red blood cells
• Mean corpuscular hemoglobin concentration (MCHC) is a measure of the hemoglobin content of red blood cells (and subsequently, their ability to carry oxygen)
• Red cell distribution width (RDW) measures the variation in size in red blood cells

In addition to these tests, other tests may be ordered to evaluate anemia, including a peripheral blood smear for morphology, iron studies, and more.

Risks and Contraindications

There are few risks related to checking a reticulocyte count other than mild discomfort, and rarely bleeding or infection related to the blood draw.

Before the Test

Blood for a reticulocyte count may be drawn in a hospital as well as many clinics.

There is no dietary or activity restriction before having a reticulocyte count done. You should bring your insurance card to your appointment and any medical records (such as previous CBCs or reticulocyte counts) you have at another clinic for comparison.

During the Test

The actual blood test usually takes only a few minutes. A lab technician will first clean the area overlying a vein (usually an arm vein) with an antiseptic and apply a tourniquet. The needle will then be inserted through your skin and into the vein. You will feel a sharp poke when the needle enters your skin and then some pressure as the sample is drawn. For some people, veins can be more difficult to access, and it may take more than one attempt to retrieve a sample.

After the blood tube is filled, the technician will remove the needle and apply pressure over your vein. A bandage will be applied to prevent further bleeding and keep the area clean and dry.

After the Test

If you have your blood drawn in a lab, you will be able to leave right after the test and return to your clinic or home to be notified of the results. Side effects are uncommon, but may include bruising at the site of the draw (a hematoma), persistent bleeding, and rarely, infection.

Interpreting Results

When your healthcare provider receives your results, she will either discuss them with you in the clinic or hospital or will call you by phone.

Reference Range

The reference range for the reticulocyte count depends on whether the hematocrit is normal or low. When anemia is not present, the absolute reticulocyte may be used. With anemia, the reticulocyte count is corrected for the low hematocrit, and if very low, is corrected for changes that occur in relation to severe anemia.

With anemia, it would be expected that the reticulocyte would be high, as the response to anemia is for the bone marrow to increase production. In this situation, a low or even a normal reticulocyte count may be a sign that the bone marrow isn't functioning as it should. Unfortunately, when anemia is present, the absolute reticulocyte count may not reflect what is really happening in the bone marrow. To compensate for this lack of clarity, a first correction is made.

Corrected Reticulocyte Count (CRC): First Correction

The corrected reticulocyte count corrects for the degree of anemia that is present (how low the hemoglobin or hematocrit is), and is calculated by multiplying the absolute reticulocyte count by the hematocrit (or hemoglobin) divided by a "normal" hematocrit or hemoglobin:

• Corrected Reticulocyte Count (Percent) = Absolute Reticulocyte Count x Patient's hematocrit / Normal Hematocrit

The reference range for corrected reticulocyte count in adults is 0.5 to 1.5%

For severe anemia (hemoglobin less than 12 or hematocrit less than 36), a second correction needed.

Reticulocyte Production Index (RPI): Second Correction

The problem with using the corrected reticulocyte count alone is that in severe anemia, reticulocytes live roughly two days in the bloodstream rather than one. Using the corrected reticulocyte count, the count could be falsely high for this reason.

The reticulocyte production index (RPI) takes into account the fact that reticulocytes will be present in the blood for a longer period of time. The RPI is derived by dividing the corrected reticulocyte count by the maturation correction, a number that estimates the lifespan in days of a reticulocyte in the bloodstream based on the degree of anemia.

Maturation Correction

The maturation correction depends on the level of anemia:

• 1 day: for a hematocrit of 36 to 45 or hemoglobin of 12 to 15
• 1.5 days: for a hematocrit of 16 to 35, or hemoglobin of 8.7 to 11.9
• 2 days: for a hematocrit of 16 to 25, or hemoglobin of 5.3 to 8.6
• 2.5 days: for a hematocrit less than 15, or hemoglobin less than 5.2

Reference Range

• An RPI of less than or equal to 2 means the bone marrow is not responding as expected (hyperproliferative anemia)
• An RPI of more than 2 or 3 means the bone marrow is trying to compensate for the anemia (hyperproliferative anemia)

Of note is that with mild anemia (hemoglobin of 12 or more or a hematocrit of 36 or higher), the maturation correction is 1 so the corrected reticulocyte count will be the same as the RPI.

Using CRC or RPI to Determine the Category of Anemia

Once the corrected reticulocyte count is calculated (and the RPI when indicated), it's possible to separate out the two broad categories of anemia—whether the bone marrow is functioning normally and trying to compensate for the anemia (compensated anemia), or if the bone marrow is sluggish for some reason (uncompensated anemia).

The reticulocyte count helps distinguish one of the two broad categories of anemia:

• Underproduction of Red Blood Cells: Anemias that occur due to inadequate production of red blood cells
• Loss of Red Blood Cells: Anemias in which an adequate number of red blood cells are being produced, but are later broken down (as with hemolysis) or lost (as with blood loss)

Causes of a High Reticulocyte Count (or CRC and RPI With Anemia)

In people without anemia, an elevated reticulocyte count may be seen with:

• Pregnancy
• High altitude
• Medications such as levodopa, antimalarials, and fever-reducing drugs
• Polycythemia or erythrocytosis (a high red blood cell count)

In the setting of anemia, an elevated reticulocyte count is actually a positive finding in some ways, as it means that the bone marrow is doing its job. A high reticulocyte count is sometimes referred to as "reticulocytosis."

With anemia, a high reticulocyte count is seen in a few situations:

• Loss of red blood cells: With blood loss, the bone marrow responds by releasing more reticulocytes to compensate, although it takes roughly two to three days to do so (in other words, a high reticulocyte count occurs with chronic blood loss or previous blood loss, but the reticulocyte count may still be low with acute blood loss)
• Reduced red blood cell survival: Conditions in which red blood cells are broken down reduce survival, and may occur due to antibodies against red blood cells (immune hemolytic anemia), due to some drugs (drug-induced hemolytic anemia), due to abnormalities in red blood cells that reduce survival (such as hereditary spherocytosis, elliptocytosis, sickle cell disease, and unstable hemoglobins), mechanical destruction (such as with artificial heart valves), due to infections (such as malaria), and more.
• Hypersplenism: The spleen may sequester red blood cells.
• Treated deficiency anemias: With iron deficiency, folate deficiency, or vitamin B12 deficiency anemias, the bone marrow usually increases production when the building blocks for red blood cells are restored.

Causes of a Low Reticulocyte Count (or CRC and RPI With Anemia)

A low reticulocyte count means that the bone marrow isn't producing red blood cells as well as it should. In people without anemia, a low reticulocyte count may be seen with some medications.

With anemia, possible causes of a low reticulocyte may include:

• Acute blood loss: Even if the bone marrow is responding appropriately to blood loss, it takes two to three days to see this effect.
• Problems in the synthesis of red blood cells: Untreated iron deficiency, vitamin B12 deficiency, and folate deficiency, conditions such as some forms of thalassemia, and with sideroblastic anemia, the anemia is due to problems synthesizing red cells. (With thalassemia major, the reticulocyte is often high instead).
• Stem cell problems: The process of hematopoiesis is that in which stem cells differentiate into the different types of blood cells. Problems with this process at any point may result in low production of red blood cells. Examples include aplastic anemia and leukemia.
• Infiltration or fibrosis of the bone marrow: When the bone marrow is infiltrated by lymphomas or cancer metastases to bone marrow (such as with breast cancer) there isn't enough room to make adequate red blood cells. With myelofibrosis, the bone marrow is replaced with fibrous tissue (scarring) leading to the same effect.
• Bone marrow suppression: If the bone marrow is suppressed, such as with the bone marrow suppression from chemotherapy, drugs to prevent transplant rejection, and some drugs for autoimmune diseases, it is unable to respond to replace red blood cells adequately. Non-chemotherapy medications such as chloramphenicol may also be a cause.
• Immune-mediated inhibition of bone marrow: Autoimmune conditions in which antibodies to self-attack the bone marrow can result in low production. An example is pure red cell aplasia.

Other conditions that may result in a low reticulocyte count include kidney disease (lack of erythropoietin), liver disease, and radiation exposure.

Next Steps

After looking at the reticulocyte count along with other blood test results, a cause may be established, or further workup may be needed to further narrow done the possible diagnoses.

Further Workup

Often times further tests will be needed.

If the reticulocyte count is low, possible tests may include:

• Iron and iron binding capacity and/or serum ferritin if the MCV is low or RDW high
• Vitamin B12 level if the MCV is high
• Bone marrow biopsy if other abnormalities are seen on the CBC (such as an abnormal white blood cell count or platelet count) your healthcare provider may be concerned about your bone marrow rather than a red blood cell problem alone
• Hemoglobin electrophoresis if thalassemia is suspected
• Blood tests to evaluate liver, kidney, and thyroid function

If the reticulocyte count is high, potential tests may include:

• Tests to look for a source of bleeding if one is not obvious (such as a colonoscopy and more)
• Tests to diagnose hemolytic anemias
• Other tests to look for hemoglobinopathies, autoimmune conditions, enzyme defects such as glucose 6 phosphate dehydrogenase deficiency (G6PD deficiency), and more

Other labs, imaging tests, or procedures may be recommended as well.

Follow-Up Reticulocyte Count

When a reticulocyte count will be repeated will depend on many factors. There are some situations in which a follow-up test is frequently done. After treatment has been initiated for iron, folate, or vitamin B12 deficiency, and once the nutrients have been supplied for manufacturing hemoglobin or red blood cells, the reticulocyte count should increase. If it does not, further evaluation to determine the reason why (or if it may be that more than one type of anemia is present) will likely be recommended.

As a follow-up after a bone marrow transplant or chemotherapy, a reticulocyte count may be done to see how well the bone marrow is responding after these treatments.

A Word From Verywell

The reticulocyte count is an extremely valuable test when trying to determine the causes of anemia. That said, corrections should be made to account for the degree of anemia or the results (and subsequently, the possible diagnoses) could be erroneous. It's important to be your own advocate and ask about this test if you believe it should be done. If you have had a reticulocyte count, make sure that any necessary calculations were done as well.