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Immature Reticulocyte Fraction

The reticulocyte count is an important indicator of effective erythropoiesis. In healthy individuals, reticulocytes circulate in the peripheral blood for 1-2 days after being released from the bone marrow, before they lose sufficient RNA to become red blood cells. During periods of increased erythropoietic demand, reticulocyte lifespan in peripheral blood increases to 3 or more days, as a result of premature release of immature or “stress” reticulocytes from the bone marrow. The recent development of automated (rather than manual) reticulocyte counts has permitted more precise counting of reticulocytes, as well as an objective measure of reticulocyte maturity, based on their RNA content. It is now possible to precisely quantitate the proportion of all reticulocytes that is immature. This is termed the “immature reticulocyte fraction”, or IRF. It is calculated as a ratio of immature reticulocytes to the total number of reticulocytes. This parameter provides a very early and sensitive index of marrow erythropoietic activity.

Major clinical applications of the IRF include the following:

  • Serial determination of IRF after bone marrow transplantation (BMT) can be used to demonstrate successful engraftment. In most cases a rise in the IRF has been shown to occur earlier than any other available laboratory parameter, including absolute neutrophil count. An increase in the IRF of more than 20% from the post BMT value suggests successful erythroid engraftment. Similarly, the IRF is a sensitive measure of early hematopoietic recovery following intensive chemotherapy.
  • The IRF can be used as an early and reliable indicator of adequacy of response to erythropoietin (EPO) therapy in patients with anemia associated with chronic renal failure, or other diseases such as AIDS and malignancy. The IRF could potentially be used to monitor response to EPO in a blood conservation program. It can also be used to monitor response to other treatments for anemia such as iron, folate and vitamin B12

Evaluation of the IRF together with the absolute reticulocyte count can provide additional useful information, as shown in the following table.


Clinical Condition


Absolute Retics

Aplastic marrow



Early erythropoietic response after anemia or engraftment after BMT

Decrease or No Change


Response to EPO Rx or early acute hemorrhage



Hemolytic anemia or hemorrhage




The IRF result is always reported together with the reticulocyte count (both percentage and absolute value.) The reference range is 0.11 – 0.38. Specimen requirement is one 5ml EDTA (lavender-top) tube of blood. IRF can be measured on the same tube used for the reticulocyte count.

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