What is being tested?
Reticulocytes are immature red blood cells produced in the bone marrow. This test measures the number and percentage of reticulocytes in the blood and serves as an indicator of the adequacy of bone marrow red blood cell (RBC) production.
The bone marrow must continually produce new red blood cells to replace those that age and degrade or are lost through bleeding. New red blood cells are produced as stem cells. They develop into reticulocytes and then into mature cells to be released from the bone marrow into the blood. Most red blood cells are fully mature before they are released from the bone marrow but about 0.5 – 2 per cent circulating in the blood are reticulocytes.
The body attempts to maintain a stable number of RBCs in circulation by continually removing old RBCs (about 120 days old) and producing new ones in the bone marrow. If this steady state is disrupted by an increased loss of RBCs or by decreased production, it will lead to anaemia. Increased loss of red blood cells may be due to acute or chronic bleeding (haemorrhage) or haemolysis. The body compensates for this loss by increasing the rate of red blood cell production. When this happens the number and percentage of reticulocytes in the blood increases until the balance is restored or until the production capacity of the marrow is reached.
Decreased red blood cell production may occur when the bone marrow is not functioning normally (due to a bone marrow disorder such as aplastic anaemia or due to marrow suppression from a variety of causes including radiation and chemotherapy treatments for cancer), because of insufficient erythropoietin (a hormone produced by the kidneys to stimulate RBC production) or because of deficiencies in certain nutrients such as iron, vitamin B12, or folate. This decreased production leads to decreased numbers of red blood cells in circulation, decreased amounts of haemoglobin (an oxygen-carrying protein inside the RBC), a decreased haematocrit (the amount of cells versus plasma in the blood) and a decreasing number of reticulocytes as old red blood cells are removed from the bloodstream but not fully replaced.
Occasionally, both the reticulocyte count and the RBC count will be increased because of excess red blood cell production. This may be due to a variety of causes including inappropriately increased production of erythropoietin, disorders that chronically produce increased numbers of red blood cells (polycythaemia vera) and even smoking.
How is it used?
The reticulocyte count is ordered to help determine if the bone marrow is responding adequately to the body's need for red blood cells (RBCs) and to help determine the cause of the anaemia and identify which type. The number of reticulocytes is compared to the total number of RBCs to calculate the percentage of reticulocytes. Because of this, the test is ordered along with an RBC count. A haemoglobin and/or haematocrit test are also usually ordered to evaluate the severity of the anaemia.
The RBC, haemoglobin, and haematocrit are often ordered routinely as part of a full blood count (FBC). Often included with the FBC is an evaluation of red cell characteristics such as cell size, volume and shape. Based on these results, a reticulocyte count may be requested to further examine RBCs. Reticulocytes can be distinguished from mature red blood cells because they still contain remnant genetic material (RNA) inside them, a characteristic not found in mature red blood cells. Circulating reticulocytes generally lose their RNA within one to two days, thus becoming mature RBCs.
In a healthy person, the reticulocyte percentage is very stable. In someone with anaemia, when the number of red blood cells decreases, the percentage of reticulocytes may appear increased compared to the overall number of red blood cells. In order to get a more accurate assessment of bone marrow function, a calculation - the calculated reticulocyte percentage (%) - is often corrected with a calculation called a corrected reticulocyte count or a reticulocyte index (RI). This compares the patient's haematocrit with a normal haematocrit value.
Reticulocyte (%) = [number of reticulocytes / number of red blood cells] x 100
Reticulocyte Index = reticulocyte count (%) x [measured haematocrit / normal haematocrit]
When is it requested?
A reticulocyte count may be requested when someone has a decreased RBC count and/or a decreased haemoglobin and haematocrit and it is necessary to evaluate bone marrow function. In someone with no apparent symptoms, these findings may be found during routine blood tests. Testing may also be ordered when someone has symptoms such as paleness, fatigue, weakness, shortness of breath and/or blood in the stool.
When a person has a known iron or vitamin B12 or folate deficiency, known kidney disease, known bone marrow suppression (such as that due to chemotherapy or bone marrow transplant) and/or is undergoing erythropoietin treatment, the reticulocyte count (and RBC count, haematocrit, and haemoglobin) may be ordered at intervals by the doctor to monitor marrow function and response to treatment.
When someone has an increased number of red blood cells and elevated haemoglobin and haematocrit, the reticulocyte count may be requested to help determine the degree and rate of overproduction of red blood cells.
What does the result mean?
The reticulocyte count 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 red blood cells and whether the bone marrow is able to respond to the extra requirement. Occasionally, results may indicate overproduction of red blood cells. If the bone marrow is responding appropriately to the demand for increased numbers of red blood cells, it will allow for the early release of more immature RBCs (reticulocytes) - thus the increased reticulocyte count. If someone haemorrhages (bleeds), the number of reticulocytes will rise a few days later in an attempt to compensate for the red cell loss. If they have chronic blood loss the number of reticulocytes will stay at an increased level as the marrow tries to keep up with the demand for new red blood cells. If the marrow is unable to keep up or is not functioning normally, the number of reticulocytes may be normal or only slightly elevated despite demand but will eventually decrease due to lack of adequate production. If the number of reticulocytes is not elevated in someone with anaemia then it is likely that there is some degree of bone marrow dysfunction or failure and/or a deficiency of erythropoietin.
The reticulocyte count gives an indication of what may be happening 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 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. In conditions causing RBC overproduction the number of reticulocytes and RBCs, the concentration of haemoglobin, and percentage of haematocrit will be increased.
Is there anything else I should know?
Patients who move to higher altitudes may have increased reticulocyte counts as their body adapts to the lower oxygen content of their new location. Smokers also may demonstrate increased number of red blood cells and reticulocytes.
Reticulocyte counts may be increased during pregnancy. Newborns have a higher percentage of reticulocytes but the number drops to near adult levels within a few weeks.
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. This method has largely been replaced by automated instruments that allow for a greater number of cells to be counted, thus enhancing the accuracy of reticulocyte counts.
Common questions
No, it must be performed and interpreted by trained personnel in the laboratory.
Yes. If anaemia is detected during a routine blood test the doctor can frequently order additional testing (including a reticulocyte test) on the same tube of blood if it can be done on the same day.
Yes. Your doctor will determine how long you should wait after a transfusion before having a reticulocyte count performed.
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 doctor to determine how well the bone marrow is functioning.
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