Clinical Information

Reticulocytes are immature erythrocytes (red blood cells: RBC) that have been released into the peripheral blood from the bone marrow after extrusion of their nucleus. The reticulocyte contains residual polyribosomes used in the formation of hemoglobin in the developing erythrocyte.

Iron deficiency suppresses hemoglobin synthesis.(1) Iron indices that rely on measurement of mature RBC may not accurately reflect acute iron status due to their long (approximately 120 days) lifespan.

Reticulocytes are differentiated from erythroblasts (RBC containing a nucleus made in the bone marrow) after hemoglobin synthesis is complete and enucleation (extrusion of the nucleus). The reticulocyte is released from the bone marrow into peripheral circulation to complete maturation through loss of its reticulum (RNA and protein visible with staining) over the course of 1 to 2 days becoming mature RBC. Ultimately, hemoglobin content in reticulocytes is more reflective of real-time hemoglobin synthesis, provided there is not an underlying hematopoietic disorder preventing the production of reticulocytes.

Reticulocyte hemoglobin may be particularly useful to evaluate iron deficiency in patients with chronic kidney disease who are on hemodialysis and receiving erythropoietin or other erythropoiesis-stimulating agents, as they are prone to chronic inflammatory states that complicate traditional iron evaluations. Studies report reticulocyte hemoglobin concentrations below 29 to 32 pg in this population have areas under the receiver-operating curve (ROC area) of 0.74-0.95 for diagnosing iron deficiency compared to low serum ferritin (ROC area range: 0.53 to 0.63) or transferrin saturation (ROC area range: 0.56 to 0.76).(2)

Iron deficiency in childhood is common yet critical to recognize early and treat. Guidelines recommend using hemoglobin in combination with either ferritin and C-reactive protein or reticulocyte hemoglobin. The advantage of using reticulocyte hemoglobin is its lower cost and does not require additional blood volume to be collected when combined with complete blood cell count testing.

Reticulocyte hemoglobin is also used to evaluate response to treatment for iron deficiency, which is one of the earliest markers of response to oral iron treatment (48 hour) in children with severe iron deficiency anemia. Measurement within 7 days from the start of oral iron is predictive of reaching reference value of hemoglobin at day 30 (3) and has been used to improve iron sufficiency rates in neonatal intensive care unit populations.(4)

Other patient populations that may benefit from reticulocyte hemoglobin measurement include those with anemia of chronic disease, postpartum, and blood donors.(2)

The reticulocyte is released from the bone marrow into peripheral circulation to complete maturation through loss of its reticulum (RNA and protein measured via fluorescence) over the course of 1 to 2 days becoming mature RBC. The immature reticulocyte fraction measures reticulocyte maturity through quantitation of fluorescence intensity. The most intense signal corresponds to the most immature reticulocytes containing the greatest amount of reticulin. When present in highest proportion of total reticulocytes can be the earliest indicator of beginning erythropoiesis.