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Reticulocyte haemoglobin equivalent (RET-He) as an early marker of responsiveness to oral iron supplementation
  1. Lulu X Pei1,
  2. Hou Kroeun2,
  3. Crystal D Karakochuk1,3
  1. 1 Food, Nutrition and Health, The University of British Columbia, Vancouver, British Columbia, Canada
  2. 2 Helen Keller International, Phnom Penh, Cambodia
  3. 3 BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada
  1. Correspondence to Dr Crystal D Karakochuk, Nutrition and Health, The University of British Columbia, Vancouver, Canada; crystal.karakochuk{at}


Aim We investigated the potential of reticulocyte haemoglobin equivalent (RET-He) as an early marker of responsiveness to iron supplementation.

Methods Data were obtained from a randomised controlled trial of daily iron supplementation in 356 Cambodian women (18–45 y) who received 60 mg elemental iron for 12 weeks. A fasted venous blood specimen was collected at baseline, 1-week and 12-week timepoints. Whole blood haemoglobin (g/L) and RET-He (pg) were measured using a Sysmex haematology analyser. RET-He measures were evaluated for their predictive ability on haemoglobin response to iron supplementation (defined as ≥10 g/L at 12 weeks). Receiver operating characteristic (ROC) curves were used to assess discrimination performance, and the area under the ROC curve (AUCROC) served as a measure of the ability of each predictor to discriminate between women likely or unlikely to elicit a haemoglobin response.

Results Predictive ability (AUCROC (95% CI)) of baseline, 1-week, and change from baseline to 1-week RET-He on haemoglobin response was 0.70 (0.63 to 0.76), 0.48 (0.41 to 0.56) and 0.81 (0.75 to 0.87), respectively. Based on the Youden index, an absolute increase in RET-He of ~1.1 pg or a percentage increase of ~4.4% over 1 week were optimal thresholds to predict responsiveness to iron supplementation.

Conclusion Single timepoint RET-He measures have poor predictive ability; however, change in RET-He after 1 week was a strong predictor of haemoglobin response among Cambodian women receiving 60 mg elemental iron and can be measured easily and quickly after only 1 week of iron therapy.

  • Hematology
  • IRON
  • Reticulocyte Count
  • Nutritional Sciences

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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  • Handling editor Tahir S Pillay.

  • Contributors LXP and CDK contributed to the conception of the study. LXP conducted the statistical analysis. LXP and CDK drafted the manuscript. HK provided operational oversight and administrative support of the trial in Cambodia. All authors have reviewed and approved the final version. CDK accepts responsiblility for the overall content as guarantor.

  • Funding The original trial was funded by the Canadian Institutes of Health Research, the Micronutrient Initiative and Sight and Life Foundation. CDK is supported by a Michael Smith Foundation for Health Research Scholar Award. LXP was funded by the University of British Columbia work-learn program.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.