Reticulocyte Hemoglobin-Equivalent Potentially Detects, Diagnoses and Discriminates between Stages of Iron Deficiency with High Sensitivity and Specificity

Abstract

Background: Iron deficiency anemia (IDA) is a global health problem affecting the quality of life of more than 2 billion individuals. The current practice guidelines diagnose and monitor IDA via conventional hematological and iron biomarkers, which take several months before they are corrected under an iron-treatment plan. Reticulocyte hemoglobin equivalent (Ret-He) is used as a marker in most new hematology analyzers to assess iron incorporation into erythrocyte hemoglobin directly. This study aims to examine the efficacy of Ret-He as a marker for iron deficiency (ID) and IDA and investigate whether Ret-He is sensitive to iron therapy. Methods: Two blood samples were drawn from 182 participants for CBC and iron profile measurements. Follow-up samples were drawn from participants with a confirmed diagnosis of ID and/or IDA. Results: Ret-He levels were lower in the ID and IDA groups compared to the control (p < 0.0001), and lower in the IDA group compared to the ID group (p < 0.0001). Ret-He was correlated with ferritin at ID level (<30.0 mg/mL; r = 0.39) and severe IDA (<13.0 ng/mL; p-value < 0.01, r = 0.57). Cut-off values of <28.25 pg for ID and <21.55 pg for IDA showed a higher specificity and sensitivity (ID; AUC: 0.99, sensitivity: 92.73%, specificity: 97.87%) and (IDA; AUC: 0.94, sensitivity: 90.63%, specificity: 92.31%). Finally, Ret-He successfully reflected the iron therapy (p < 0.001) when compared to hemoglobin (Hb) (p = 0.1). Conclusions: Ret-He is a potential marker for detecting and diagnosing different stages of ID with high validity and is very sensitive in reflecting the iron incorporation in a short time.

Reticulocyte Hemoglobin as a Screening Test for Iron Deficiency Anemia: A New Cut-Off

“…Therefore, using blood samples to determine Hb content in reticulocytes is helpful to analyze and assess iron levels via reticulocytes [ 23 ]. The assessment of hemoglobin content in reticulocytes can accurately reflect iron levels [ 24 ].…”

“…Ferritin can play a role when C-reactive protein and IL-6 (a critical cytokine)act as pro-inflammatory cytokines by mediating fever and the acute inflammatory response to lower the fever and critical cytokine levels, which in turn reduces the hyperinflammatory response [ 40 , 41 ]. In most laboratories currently, the serum ferritin level is used to indicate the body’s iron store as it is a non-invasive method that provides reliable results, near to the invasive gold-standard method for body iron store; however, the difference in cut-off of ferritin levels to define depleted iron stores can also be seen [ 24 , 41 ].…”

“…New hematology analyzers can measure the hemoglobin content within the reticulocytes through the principles of fluorescence flow cytometry combined with reportable/diagnostic parameters to provide valuable diagnostic information. Such information is evaluated internally in the laboratory to check the results and to complete the diagnosis findings [ 24 , 48 ].…”

Comparison of Standard and New Iron Status Biomarkers: A Prospective Cohort Study in Sepsis Patients

“…Ret Hb equivalent is a credible marker for determining the presence and severity of iron deficiency in different populations of patients: children [ 16 ] and adults [ 18 ]. Its validity has been reported [ 19 , 20 ].…”

Reticulocyte hemoglobin equivalent as a marker to assess iron deficiency: A large pediatric tertiary care hospital study

“…Several recent pediatric and adult studies that focus on the utilization of Ret‐He to diagnose ID with or without anemia have identified Ret‐He as a potential useful marker 12,14–18 . However, various methods and cutoffs for ferritin with or without TSAT were applied to define groups according to ID status, which reflect the lack of, but critically needed, established “gold standard” to define ID.…”