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Reticulocyte

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Reticulocytes are immature red blood cells.

Reticulocytes are immature anucleated, erythroid cells (RBCs) with residual detectable amounts of RNA, thereby capable of producing hemoglobin despite anucleation.

Bone marrow reticulocytes have an average maturation period of 2.5 days.

After one day in the circulation, reticulocytes lose their ribosomal network and become mature RBCs.

Comprises about 1% of the peripheral blood cells.

Develop and mature in the red bone marrow and then circulate for about a day in the blood stream before developing into mature red blood cells.

Have a reticular, mesh like, network of ribosomal RNA seen with a methylene blue stain.

Do not have a nucleus.

Appear slightly bluer than other red cells when looked at with the normal Romanowsky stain.

Slightly larger than more mature red blood cells.

Reticulocytes are less efficient at carrying oxygen as mature red cells, and they are less deformable, causing impaired transit through capillary beds.

The normal range is 0.5% to 1.5%.

The reticulocyte count is an indicator of bone marrow activity, because it represents recent production.

The reticulocyte count, and the reticulocyte production index that can be calculated from it, can be used to determine whether a production problem is contributing to the anemia, and can also be used to monitor the progress of treatment for anaemia.

Increased production of red blood cells to overcome chronic or severe loss of mature red blood cells, such as in a hemolytic anaemia, people often have a high percentage of reticulocytes.

High number of reticulocytes is referred to as as reticulocytosis.

Abnormally low numbers of reticulocytes indicates poor production of red blood cells and can be due to innumerable processes.

The reticulocyte index, or reticulocyte production index, is a calculation that helps to alleviate the effect of the premature release of reticulocytes by taking into account maturation time of reticulocytes, in addition to correcting for the degree of anemia.

The absolute reticulocyte count and corrected reticulocyte percentage, as a marker of RBC production, provide an initial evaluation as to whether anemia is due to loss of RBCs or inadequate production.

The absolute reticulocyte count is the number of reticulocytes in a volume of blood, which is a marker of RBC production.

Corrected reticulocyte percentage = reticulocyte percentage x [actual hematocrit/normal hematocrit (usually 45)

Reticulocyte index = corrected reticulocyte percentage/maturation time in peripheral blood in days (correction factor is usually 2).

In appropriate responses to peripheral RBC loss, such as bleeding or hemolysis, increased RBC production from the bone marrow is expected, and reticulocytosis occurs.

Failure of the adequate bone marrow response to anemia usually correlates with a low reticulocyte count and is associated with bone marrow–related disorders.

Increased reticulocyte count reflects ongoing or recent RBC production activity due to bleeding, hemolysis, response to therapy with iron supplementation, vitamin B-12 or folic acid, erythropoietin stimulation, , bone marrow recovery following chemotherapy.

A decreased reticulocyte count reflects decreased RBC production, which may result from: iron, B12, folic acid deficiencies, decreased erythropoietin levels, aplastic anemia or bone marrow failure syndromes, radiation therapy, bone marrow replacement disorders, by benign or malignant processes.

The reticulocyte index, or reticulocyte production index (RPI), which is corrected or adjusted for both premature release of reticulocytes from the bone marrow and the degree of anemia, provides an assessment for adequate bone marrow response to anemia.

An increased RPI of >3can be seen in:

Hemolytic anemias

Recent hemorrhage

Marrow response to therapy

A decreased RPI of < 2) can be seen in the following:

Hypoproliferative disorders

Ineffective erythropoiesis, as seen in megaloblastic anemia

Some automated hematology analyzers report an immature reticulocyte fraction (IRF), which provides information similar to the reticulocyte index.

Immature reticulocyte function (IRF) is a quantitative measurement of the RNA content of the reticulocytes.

Immature reticulocytes contain a higher RNA content than more mature reticulocytes.

An increase in reticulocytes with the highest RNA content reflects an increased IRF, and early marrow recovery from the conditioning regimens of stem cell transplant, cancer chemotherapy, or treatment for nutritional anemias.

IRF helps to evaluate ineffective erythropoiesis and to differentiate megaloblastic anemia or myelodysplasia, and can also be used with the reticulocyte count to narrow the causes of anemia.

A low absolute reticulocyte count with low IRF is associated with severe aplastic anemia or renal failure.

A reticulocytopenia with a high IRF indicates repopulating marrow.

Reticulocytosis with a high IRF is seen in acute hemolysis or blood loss, while a low to normal absolute reticulocyte count and high IRF is associated with dyserythropoiesis, as seen in an early response to iron therapy.

The reticulocyte count is used to estimate the degree of effective erythropoiesis, which can be reported as absolute reticulocyte count or as a reticulocyte percentage.

The reference range of the reticulocyte percentage in adults is 0.5%-1.5%, and the reference range of the corrected reticulocyte percentage in adults is 0.5%-1.5%.

The reticulocyte count is used to estimate the degree of effective erythropoiesis, which can be reported as absolute reticulocyte count or as a reticulocyte percentage.

In the presence of anemia, the reticulocyte percentage is spuriously high and may not reflect the bone marrow response to anemia; therefore, the value is adjusted to a corrected reticulocyte percentage based on the patient’s hematocrit.

The absolute reticulocyte count is reported by automated hematology analyzers.

Spuriously elevated reticulocyte percentage and absolute reticulocyte count can result if the time reticulocytes spend in the blood circulation prior to maturation is prolonged.

In general, reticulocytes mature within one day of being released from bone marrow.

With stress erythropoiesis, as in a high erythropoietin level in persons with severe anemia, reticulocytes are prematurely released from bone marrow to the blood circulation, increasing the number of days that reticulocytes stay in the blood circulation and can result in a spuriously high reticulocyte count.

The reticulocyte index, or reticulocyte production index, is a calculation that helps to account for the effect of the premature release of reticulocytes by taking into account maturation time of reticulocytes, in addition to correcting for the degree of anemia.

The absolute reticulocyte count and corrected reticulocyte percentage, as a marker of RBC production, provide an initial evaluation as to whether anemia is due to loss of RBCs or inadequate production.

In appropriate responses to peripheral RBC loss, such as bleeding or hemolysis, increased RBC production from the bone marrow is expected, and reticulocytosis occurs.

Failure of the adequate bone marrow response to anemia usually correlates with a low reticulocyte count and is associated with bone marrow–related disorders.

Increased reticulocyte count reflects ongoing or recent RBC production activity due to bleeding, hemolysis, response to therapy with iron supplementation, vitamin B-12 or folic acid, erythropoietin stimulation, , bone marrow recovery following chemotherapy.

A decreased reticulocyte count reflects decreased RBC production, which may result from: iron, B12, folic acid deficiencies, decreased erythropoietin levels, aplastic anemia or bone marrow failure syndromes, radiation therapy, bone marrow replacement disorders, by benign or malignant processes.

The reticulocyte index, or reticulocyte production index (RPI), which is corrected or adjusted for both premature release of reticulocytes from the bone marrow and the degree of anemia, provides an assessment for adequate bone marrow response to anemia.

An increased RPI of >3can be seen in:

Hemolytic anemias

Recent hemorrhage

Marrow response to therapy

A decreased RPI of < 2) can be seen in the following:

Hypoproliferative disorders

Ineffective erythropoiesis, as seen in megaloblastic anemia

Some automated hematology analyzers report an immature reticulocyte fraction (IRF), which provides information similar to the reticulocyte index.

Immature reticulocyte function (IRF) is a quantitative measurement of the RNA content of the reticulocytes.

Immature reticulocytes contain a higher RNA content than more mature reticulocytes.

An increase in reticulocytes with the highest RNA content reflects an increased IRF, and early marrow recovery from the conditioning regimens of stem cell transplant, cancer chemotherapy, or treatment for nutritional anemias.

IRF helps to evaluate ineffective erythropoiesis and to differentiate megaloblastic anemia or myelodysplasia, and can also be used with the reticulocyte count to narrow the causes of anemia.

A low absolute reticulocyte count with low IRF is associated with severe aplastic anemia or renal failure.

A reticulocytopenia with a high IRF indicates repopulating marrow.

Reticulocytosis with a high IRF is seen in acute hemolysis or blood loss, while a low to normal absolute reticulocyte count and high IRF is associated with dyserythropoiesis, as seen in an early response to iron therapy.

Automated hematology analyzers can measure the reticulocyte-specific hemoglobin content as mean reticulocyte hemoglobin content (CHr) or reticulocyte hemoglobin equivalent (Ret-He), depending on the type of instrument used.

CHr and Ret-He, are comparable but not identical parameters.

They provide information about functional iron available for incorporation into hemoglobin within RBCs over the previous 3-4 days.

A decreased value reflects reduced cellular hemoglobin content and identifies functional iron deficiency.

CHr and Ret-He are the strongest predictors of iron deficiency anemia in children.

The reticulocyte-specific hemoglobin content, as CHr or Ret-HE, is useful to detect functional iron deficiency in complex clinical settings, such as chronic inflammation and chronic renal disease, since serum f2241itin can be falsely elevated as an acute-phase reactant despite low body iron storage, and there is physiologic variation of serum iron and total iron-binding capacity.

The reticulocyte-specific hemoglobin content may be a better predictor of marrow iron stores than traditional serum iron parameters when red blood cells are not macrocytic.

The reticulocyte-specific hemoglobin content is more sensitive predictor of iron deficiency than hemoglobin for screening infants and adolescents for iron deficiency prior to the development of anemia

The absolute reticulocyte count is the number of reticulocytes in a volume of blood, which is a marker of RBC production.

Corrected reticulocyte percentage = reticulocyte percentage x [actual hematocrit/normal hematocrit (usually 45)

Reticulocyte index = corrected reticulocyte percentage/maturation time in peripheral blood in days (correction factor is usually 2).

Hematocrits and corresponding correction factors are as follows:

Hematocrit, 45: Factor of 1 Hematocrit, 35: Factor of 1.5 Hematocrit, 25: Factor of 2 Hematocrit, 15: Factor of 2.5

Immature reticulocyte fraction (IRF) is defined as the least mature fraction of reticulocytes and is a mean of assessing reticulocyte fraction.

The maturity of reticulocytes is classified based on the amount of stained RNA content by automated machine using fluorescence.

The most immature reticulocytes, produced when erythropoietin levels are high, contain more RNA content and fluoresce more strongly than the more mature ones normally present in the peripheral blood.

IRF can be used to help classify the cause of anemia, to assess for effective erythropoiesis, and to evaluate for marrow recovery.

The mean reticulocyte hemoglobin content (CHr) and reticulocyte hemoglobin equivalent (Ret-He) are two equivalent parameters that capture the amount of hemoglobin available to the reticulocytes within the previous 3-4 days, and correlate with the functional availability of iron in the bone marrow.

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