Ret-He: Reticulocyte hemoglobin equivalent – Marker for iron deficiency in ADHF

It is well known that iron deficiency is associated with poor outcome in acute decompensated heart failure. Different criteria like serum ferritin less than 100 ng/mL or 100-299 ng/mL with transferrin saturation less than 20% have been used to define iron deficiency. Inflammation which is common in heart failure may hinder serum ferritin values [1]. Another marker which has been proposed is reticulocyte hemoglobin equivalent (Ret-He) which is thought to reflect the iron content in reticulocytes.

In a study of 225 patients with ADHF from Japan, median left ventricular ejection fraction was 37%. Median hemoglobin level was 10.6 g/dL and serum iron was 7.1 μmol/L. Among these patients, median Ret-He levels were lower in those with iron deficiency than in those without iron deficiency [2]. By receiver-operating characteristic analysis, they found the screening cut-off of Ret-He as 32.4 pg both for transferrin saturation less than 20% and serum ferritin less than <100 ng/mL. Authors concluded that measurement of Ret-He is an inexpensive and cost-effective way of assessing iron deficiency in ADHF.

An older study in cancer patients had also found that a threshold of 32 pg/cell Ret-He ruled out iron deficiency with a high negative predictive value of 98.5%. NPV was 100% in a subpopulation with low reticulocyte count though the number in the subgroup was low [3].

Reference

1. Masini G, Graham FJ, Pellicori P, Cleland JGF, Cuthbert JJ, Kazmi S, Inciardi RM, Clark AL. Criteria for Iron Deficiency in Patients With Heart Failure. J Am Coll Cardiol. 2022 Feb 1;79(4):341-351. doi: 10.1016/j.jacc.2021.11.039. PMID: 35086656.
2. Okuno K, Naito Y, Ohno J, Sunayama I, Matsumoto Y, Soyama Y, Oboshi M, Manabe E, Azuma K, Sugahara M, Min KD, Asakura M, Ishihara M. Reticulocyte hemoglobin equivalent is an easily applicable marker for detecting iron deficiency in patients with acute decompensated heart failure. Am Heart J Plus. 2023 Oct 6;35:100332. doi: 10.1016/j.ahjo.2023.100332. PMID: 38511184; PMCID: PMC10945886.
3. Peerschke EI, Pessin MS, Maslak P. Using the hemoglobin content of reticulocytes (RET-He) to evaluate anemia in patients with cancer. Am J Clin Pathol. 2014 Oct;142(4):506-12. doi: 10.1309/AJCPCVZ5B0BOYJGN. PMID: 25239418; PMCID: PMC4962332.