Reticulocyte Hemoglobin Equivalent Useful in Detecting Iron Deficiency Anemia

Choladda V. Curry, MD

Credit: Baylor College of Medicine

Reticulocyte hemoglobin equivalent (RET-He) was found to be a useful and reliable marker with high sensitivity and acceptance specificity in confirming iron deficiency anemia (IDA) in a recent large pediatric study.¹

Among a cohort of >3000 adolescents, the results showed RET-He, a parameter readily accessible from certain routine hematology analyzers, significantly correlated with other markers of iron metabolism and relevant complete blood count parameters used for the evaluation of iron deficiency and IDA.

“In the largest pediatric cohort to date, we confirmed the significant relationship of Ret-He with biochemical and CBC parameters, as well as the usefulness of Ret-He as a screening marker for iron deficiency and IDA in a pediatric population,” wrote the investigative team, led by Choladda V. Curry, MD, department of pathology and immunology, Baylor College of Medicine and Texas Children’s Hospital.

The most common nutrition deficiency both globally and in the United States, early detection of iron deficiency is key to avoiding adverse effects in an affected individual, including developmental delay, fatigue, and poor physical performance.² There is no singular optimal measure of iron status – complete blood count is typically the first routine test due to symptoms of fatigue, where results of microcytosis can trigger further testing to evaluate iron deficiency.

RET-HE correlates to iron availability for marrow erythropoiesis – a low RET-HE level might indicate an early sign of iron-deficient erythropoiesis status. Thus, Curry and colleagues evaluated the performance of RET-He as a potential diagnostic to assess iron deficiency and IDA in a large pediatric cohort.¹

The team retrospectively studied 3158 pediatric patients (median age, 8.5 years; 60% female) at 3 hospital locations from January 2015 to January 2021. The primary criterion for patient status of iron deficiency was low ferritin, defined as below the reference interval for age group (<2.5th percentile); to account for iron deficient cases where ferritin was normal or high, the secondary criteria included a combination of low iron, low mean corpuscular volume (MCV), and a high total iron binding capacity.

Statistical analysis was performed to evaluate the association of RET-He with other relevant complete blood count and iron panel parameters, to compare the levels of RET-He in iron deficient cohorts to controls, and to assess the sensitivity and specificity of RET-He in all cohorts.

In the total cohort, 998 (31.6%) patients had no iron deficiency or anemia, and 1289 (40.8%) had iron deficiency. In the iron-deficient group, 291 (9.2%) were without anemia and 998 (31.6%) had anemia (IDA). Upon analysis, investigators identified a significant positive correlation of RET-HE with ferritin in all patient cohorts (r = .61; P = .001), as well as a significant positive correlation to transferrin saturation.

Moreover, the median RET-He, ferritin, iron, (TSAT), MCV, and hemoglobin were lower in the IDA group than in iron deficiency without anemia, and in all patients with iron deficiency, compared to the control group. Post-hoc analyses revealed significant differences between the iron deficient cohorts and all other groups, except for iron deficiency without anemia and non-iron deficiency anemia (P = .002).

In receiver operating characteristic (ROC) curve analysis, the RET-HE values of ≤30.0pg in all iron deficient cohorts resulted in a sensitivity of 90.2%, specificity of 59.5%, and area under curve (AUC) of 0.88. A cutoff value of ≤30.8pg allowed the diagnosis of iron deficiency without anemia with a sensitivity of 80.8%, a specificity of 51.1%, and an AUC of 0.70.

A cutoff value of ≤27.4pg had the best diagnostic performance for screening IDA, with a sensitivity of 90.1%, specificity of 80.9%, and an AUC of 0.93. The non-iron deficient anemia group with a cutoff value of ≤30.8pg yielded the least sensitivity of 75.0% and poor specificity of 51.1%, with an AUC of 0.71.

Based on these analyses, Curry and colleagues suggest RET-He could be considered a complimentary test in the management of iron deficiency and IDA among pediatric populations.

“RET-He is a useful and practical marker with high sensitivity and acceptable specificity to help identify IDA,” investigators wrote. “Future studies assessing the use of RET-He in combination with other parameters may help improve further the performance of RET-He in early detection of iron deficiency.”

References

1. Poventud-Fuentes I, Chong TH, Dowlin M, Devaraj S, Curry CV. Reticulocyte hemoglobin equivalent as a marker to assess iron deficiency: A large pediatric tertiary care hospital study [published online ahead of print, 2023 Oct 18]. Int J Lab Hematol. 2023;10.1111/ijlh.14188. doi:10.1111/ijlh.14188
2. Neef V, Schmitt E, Bader P, et al. The reticulocyte hemoglobin equiva- lent as a screening marker for iron deficiency and iron deficiency ane- mia in children. J Clin Med. 2021;10(16):3506