Reticulocyte Hemoglobin Content (RET-He): Clinical Value of a Key Parameter in Reticulocyte Evaluation

By: Jolanta Kunicka, PhD, Director of Scientific Marketing, and Margaret Fischer, RN, BSN, MS, Senior Manager of Clinical Support at Sysmex America Inc.
Monday, January 18, 2016

The complete blood count (CBC) with reticulocytes, one of the most frequently ordered lab tests, may be underutilized by physicians for diagnostic purposes.

In the United States, 3.4 million people have anemia, and 2 billion people are affected globally.1 In many of these individuals, anemia is due to iron deficiency (ID/IDA). New laboratory technologies are providing a more in-depth evaluation of immature cell forms, expanding the number of reportable parameters included in CBC and reticulocyte results. The use of comprehensive reticulocyte parameters, especially reticulocyte hemoglobin content (RET-He), can provide physicians with additional information to assist with earlier detection, differential diagnosis and management of ID/IDA. This data can be beneficial in the management of high-risk populations, such as young children, patients with chronic disease, presurgical patients and those with many other conditions.

What Is a Comprehensive Reticulocyte Evaluation?

Three parameters can be reported with every reticulocyte order to provide physicians with the comprehensive information to assess the rate of red cell production and hemoglobinization. The comprehensive evaluation includes a reticulocyte count (RET #, %), which indicates the quantity of circulating reticulocytes, the immature reticulocyte fraction (IRF), which indicates the rate of production of reticulocytes, and the RET-He, which indicates cell hemoglobinization, reflecting the quality of the newly produced reticulocytes. These three parameters can enable the practitioner to differentiate iron-dependent hemoglobinization from erythropoiesis. These value-added tests are quickly obtained, and they are inexpensive to run.

The hemoglobin and hematocrit (H+H) are relatively static parameters and may change too slowly to be used as the primary indicators of the patient’s rate of erythropoiesis or cellular iron status.

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Prevention of Anemia During Presurgical Screening

A significant example of one clinical application of the use of RET-He is in presurgical screening for anemia. Due to the high prevalence of anemia in pre- and postsurgical patient populations, the condition is one of the major causes of hospital readmissions. It is well documented that patients with anemia have worse outcomes, and it stands to reason that appropriate screening and treatment for iron deficiency and iron deficiency anemia in the presurgical setting is warranted.

In 2009, Muusze R et al.2 examined the utility of adding RET-He to their pre- and postoperative protocols in an effort to detect and treat iron deficiency anemia at the earliest possible time. In the study, anemia defined as Hb <13g/dL was treated presurgically or postsurgically with a combination of erythropoiesis stimulating agents (ESA) and/or intravenous (IV) iron. RET-He showed a response to therapy within three days, as opposed to Hb that took up to three weeks to show a response. The outcome of the recovery plan relied, in part, on the identification of nonresponders to ESA therapy. Results from this study may have applicability to other patient groups who have sudden demand for increased erythropoiesis, similar to the demands of blood loss or ESA administration. This is just one example of the clinical utility of the RET-He parameter in the differential screening, diagnosis and treatment of anemia. Other applications may include the management of high-risk populations such as young children, patients with chronic disease and those with many other conditions.


There is little doubt that laboratories offering RET-He results can help physicians better identify and monitor therapy in iron deficiency and iron deficiency anemia. The RET-He test has been shown to be simple, reliable and available at a minimum cost, and it is automatically reported as part of the comprehensive reticulocyte evaluation. It has been shown to be an early indicator of either decreasing or increasing iron availability in the bone marrow. Physicians may be able to gauge a patient’s response to therapy in days, instead of weeks, and adjust the plan of care accordingly.

Read more at The Use of RET-He in the Value-Driven Laboratory at