CBC Biomarkers: Reticulocytes

Optimal Takeaways

Reticulocytes are red blood cells that have not yet fully developed. Production of reticulocytes increases when the bone marrow needs to replace RBCs, e.g., in the event of blood loss or anemia, and decreases when bone marrow function is compromised. Measurement of reticulocytes is expressed as a percentage of circulating RBCs.

Standard Range: 0.7-2.8%

The ODX Range: 0.7-2.8%

Low reticulocytes (reticulocytopenia) are associated with bone marrow failure, chronic infection, cirrhosis, malignancy, radiation therapy, adrenocortical or anterior pituitary hypofunction. Reticulocytes are also low in the presence of certain anemias including aplastic anemia, megaloblastic anemia (e.g., pernicious anemia, vitamin B12 and/or folate deficiency); hypochromic anemias (e.g., iron deficiency, sideroblastic, and anemia of chronic disease) (Pagana 2019, Riley 2001), and myelodysplastic syndromes (Rai 2022).

High reticulocytes (reticulocytosis) are associated with blood loss or hemorrhaging, post-splenectomy, pregnancy, leukemia, hemolytic anemias (e.g., sickle cell, thalassemia, G6PD deficiency, and hypersplenism), and during recovery from nutrient-related anemias as RBC production recovers. In such cases, the bone marrow is functional (Pagana 2019, Riley 2001).

Overview

Reticulocytes are immature red blood cells that develop within the bone marrow for 1-3 days and then mature within 1-2 days following their release into circulation (Rai 2022). Reticulocyte concentration in the blood reflects bone marrow function and can indicate increased production in response to anemia, or the need for RBC replacement following destruction or loss. If levels are consistently low in the presence of anemia, the cause should be investigated including aplastic anemia or nutrient deficiency such as iron or vitamin B12 (Pagana 2019).

If reticulocytes are consistently high in the presence of anemia, then bleeding or hemolysis may be occurring, or the bone marrow may be actively responding to therapy, e.g., iron supplementation. If the bone marrow has not yet fully responded, the percentage of reticulocytes will appear falsely elevated (Rai 2022, Turner 2022, Gaur 2021).

The mean normal value for reticulocytes is 1-1.5% with an upper normal of 3% (Riley 2001) though most healthy individuals maintain a level between 0.5-2.5% (Rai 2022).

References

Gaur, Malvika, and Tushar Sehgal. “Reticulocyte count: a simple test but tricky interpretation!.” The Pan African medical journal vol. 40 3. 2 Sep. 2021, doi:10.11604/pamj.2021.40.3.31316

Pagana, Kathleen Deska; Pagana, Timothy J.; Pagana, Theresa N. Mosby's Diagnostic and Laboratory Test Reference. Elsevier Health Sciences. 2019.

Rai, Dipti, et al. “Histology, Reticulocytes.” StatPearls, StatPearls Publishing, 17 February 2022.

Riley, R S et al. “Reticulocytes and reticulocyte enumeration.” Journal of clinical laboratory analysis vol. 15,5 (2001): 267-94. doi:10.1002/jcla.1039

Turner, Jake, et al. “Anemia.” StatPearls, StatPearls Publishing, 9 January 2022.