Reticulocyte

Reticulocyte
Peripheral blood; Reticulocyte. © Image courtesy of Nivaldo Medeiros MD and published with permission

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Varun Kumar, M.B.B.S. [2]

Overview

Reticulocytes are immature red blood cells, typically composing about 1% of the red cells in the human body. Reticulocytes 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. Like mature red blood cells, reticulocytes do not have a cell nucleus. They are called reticulocytes because of a reticular (mesh-like) network of ribosomal RNA that becomes visible under a microscope with certain stains such as new methylene blue.

Differential Diagnosis of Reticulocytosis

An elevation in the number of reticulocytes is called reticulocytosis. There are numerous causes of reticulocytosis.

By Organ System

Cardiovascular	No underlying causes
Chemical / poisoning	No underlying causes
Dermatologic	No underlying causes
Drug Side Effect	Antimetabolite medication, Chemotherapy, Chronic alcoholism, Drug induced anemia, Drug induced bone marrow suppression, Methotrexate ,Olsalazine, (Rheumatrex)
Ear Nose Throat	No underlying causes
Endocrine	Addison's disease (chronic adrenal insufficiency), Adrenocorticoid (Isolated) Deficiency, androgen deficiency, Hypogonadism, Hypothyroidism (myxedema)
Environmental	No underlying causes
Gastroenterologic	Liver disease/Liver disorders
Genetic	Klinefelter's syndrome
Hematologic	Acquired sideroblastic anemia, Acute Myelogenous/Blastic Leukemia AML, Anemia of chronic disease, Anemia of uremia, Aplastic anemia, congenital aplastic anemia, congenital folate malabsorption, Fanconi's pancytopenia-dysmelia syndrome, Folate depletion, Folic acid deficiency anemia, Hemoglobin H disease, Hereditary elliptocytosis, Hereditary sideroblastic anemia, Iron deficiency anemia, Leukemia, Lymphoma/malignant, Megaloblastic anemia, Megaloblastic anemia of pregnancy, Myelophthisic anemia, Myeloproliferative disease, non-Hodgkins lymphoma, Pellagra/niacin deficiency, Pernicious anemia, Primary Myelofibrosis/Myeloid metaplasia, Sideroblastic anemia-Siderochrestic, Refractory megaloblastic anemia, Secondary myelofibrosis, Thalassemia major, Thalassemia minor, Thalassemia-hemoglobin C disease, Vitamin B12 deficiency
Iatrogenic	No underlying causes
Infectious Disease	Abscesses, Bacteremia/Septicemia, Infected organ, Parvovirus Infection/Parvovirus B19, Posthepatitic aplastic anemia, Tuberculosis of bone marrow
Musculoskeletal / Ortho	No underlying causes
Neurologic	No underlying causes
Nutritional / Metabolic	Anemia of malnutrition, Anemia of uremia, Folate depletion, Folic acid deficiency anemia, Folic acid dependency/metabolic defect, Impaired folic acid metabolism, Inadequate Folic acid in diet, Iron deficiency anemia, Iron deficient diet, Kwashiorkor (protein deficiency,severe), Malnutrition/Starvation, Malabsorption of folic acid, Megaloblastic anemia of pregnancy Pellagra/niacin deficiency, Vitamin B12 deficiency
Obstetric/Gynecologic	Megaloblastic anemia of pregnancy
Oncologic	Acute Myelogenous/Blastic Leukemia AML, Leukemia, Lymphoma/malignant, Myeloproliferative disease, non-Hodgkins lymphoma, Primary Myelofibrosis/Myeloid metaplasia
Opthalmologic	No underlying causes
Overdose / Toxicity	Antimetabolite medication, Chronic alcoholism, Chemotherapy, Drug induced anemia, Drug induced bone marrow suppression, Methotrexate (Rheumatrex)
Psychiatric	No underlying causes
Pulmonary	No underlying causes
Renal / Electrolyte	Anemia of uremia, Chronic renal failure
Rheum / Immune / Allergy	No underlying causes
Sexual	Hypogonadism
Trauma	No underlying causes
Urologic	No underlying causes
Miscellaneous	Lead poisoning, Tetraethyl lead poisoning

In Alphabetical Order

• Acquired sideroblastic anemia
• Addison's disease (chronic adrenal insufficiency)
• Adrenocorticoid (Isolated) Deficiency
• AML (AML)
• Androgen insensitivity syndrome
• Anemia of chronic disease
• Anemia of malnutrition
• Anemia of uremia
• Antimetabolite medication Administration/Toxicity
• Aplastic anemia
• Aplastic anemia crisis
• Bacteremia/Septicemia
• Chemotherapy, cancer (anti-neoplastic)
• Chronic alcoholism
• Chronic liver disease
• Chronic renal failure
• Combined system disease/pernicious anemia
• Congenital aplastic anemia
• Congenital folate malabsorption
• Drug induced anemia
• Drug induced Bone marrow suppression.
• Fanconi's pancytopenia-dysmelia syndrome
• Folate depletion
• Folic acid deficiency anemia
• Folic acid dependency/metabolic defect
• Hemoglobin H disease
• Hereditary elliptocytosis
• Hereditary sideroblastic anemia
• Hypogonadism,
• Hypothyroidism (myxedema)
• Impaired folic acid metabolism
• Inadequate Folic acid in diet
• Infected organ, Abscesses
• Iron deficiency anemia
• Iron deficient diet
• Klinefelter's syndrome
• Kwashiorkor (severe protein deficiency)
• Lead poisoning
• Leukemia
• Liver disease/Liver disorders
• Malabsorption of folic acid
• Malnutrition/Starvation
• Megaloblastic anemia
• Megaloblastic anemia of pregnancy
• Methotrexate (Rheumatrex) Administration/Toxicity
• Myeloid metaplasia pathophysiology
• Myelophthisic anemia
• Myeloproliferative disease
• Non-Hodgkins lymphoma/malignant,
• Parvovirus Infection/Parvovirus B19
• Pellagra/niacin deficiency
• Pernicious anemia
• Posthepatitic aplastic anemia
• Postirradiation effects
• Primary Myelofibrosis/Myeloid metaplasia
• Radiation exposure
• Refractory megaloblastic anemia
• Secondary myelofibrosis
• Severe, acute Radiation sickness
• Sideroblastic Anemia Siderochrestic
• Tetraethyl lead poisoning
• Thalassemia major
• Thalassemia minor
• Thalassemia-hemoglobin C disease
• Tuberculosis of bone marrow
• Vitamin B12 deficiency

Diagnosis

Laboratory Findings

• Reticulocytes appear slightly bluer than other red cells when looked at with the normal Romanowsky stain.
• Reticulocytes are also slightly larger, which can be picked up as a high MCV (mean corpuscular volume) with a full blood count done by a trained medical scientist, who has specialized in haematology, or a machine.
• The reticulocyte count is the percentage of circulating red blood cells that are in the reticulocyte stage.
• To accurately measure reticulocyte counts, automated counters that use lasers mark cell samples with fluorescent dye that marks RNA and DNA (such as thiazole orange).
• This distinguishes reticulocytes as the middle ground of dye response to laser light, between red blood cells (which have neither RNA nor DNA) and lymphocytes (which have a large amount of DNA, unlike reticulocytes).
• The normal range of values for reticulocytes in the blood depends on the clinical situation and the lab, but broadly speaking is 0.5% to 1.5%.
• However, if a person has anaemia, their reticulocyte percentage should be higher than "normal" if the bone marrow's ability to produce new blood cells remains intact.
• Thus, calculating the reticulocyte production index is an important step in understanding whether the reticulocyte count is appropriate or inappropriate to the situation.
• This is often a more important question than whether the percentage is in the normal range; for instance, if someone is anemic but only has a reticulocyte percentage of 1%, this means that the bone marrow is likely not producing new blood cells at a rate that will correct the anemia.
• The number of reticulocytes is a good indicator of bone marrow activity, because it represents recent production.
• This means that 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 anaemia, and can also be used to monitor the progress of treatment for anaemia.
• The specimen requirement for a reticulocyte count is EDTA anti-coagulated whole blood (lavender-top bottle if using the Vacutainer®, Vacuette® or Monoject® systems; red-top if using the S-Monovette® system).
• When there is an increased production of red blood cells to overcome chronic or severe loss of mature red blood cells, such as in a haemolytic anaemia, people often have a markedly high number and percentage of reticulocytes.
• A very high number of reticulocytes in the blood can be described as reticulocytosis.
• Abnormally low numbers of reticulocytes can be attributed to chemotherapy, aplastic anaemia, pernicious anaemia, bone marrow malignancies, problems of erythropoietin production, or other causes of anaemia due to poor RBC production.

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  Reticulocyte (Courtesy of Melih Aktan M.D.)

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  Reticulocyte (Courtesy of Melih Aktan M.D.)

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  Reticulocyte

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  Erythrocyte

Related Chapters

• Reticulocyte index

References

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