The Role of Reticulocyte Hemoglobin Content in Diagnosing Iron Deficiency in Childhood Cancer

Abstract

Background The prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) in children with cancer is not well studied. The detection of ID and IDA using sensitive laboratory tools may facilitate early diagnosis and treatment in this cohort. In this regard, reticulocyte hemoglobin (Ret-He) content serves as a cost-effective measurement that remains unaffected by inflammation, unlike the ferritin test.

Aim The objective of this study is to analyze the role of Ret-He as a diagnostic tool to identify functional and absolute ID and IDA in children with cancer.

Methods We conducted a cross-sectional study in children aged 0 to 18 years. Blood samples were collected to compare Ret-He values with iron status, reflected by hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), serum iron (SI), total iron binding capacity (TIBC), and ferritin and transferrin saturation. The overall discriminative power of Ret-He in detecting ID and IDA was assessed using receiver operating characteristic analysis.

Results Of the 135 children included in the study, 58 (43.0%) had anemia. Among them, 20 (14.8%) had IDA (8 [5.9%] absolute and 12 [8.9%] functional), while 25 (18.5%) had ID (16 [11.9%] absolute and 9 [6.7%] functional). The Ret-He value was significantly related to iron status (p ≤ 0.002). Ret-He was also shown to have a significant correlation with the abovementioned hematological parameters (p = 0.000), except TIBC. Multivariate analysis revealed a significant relationship between Hb (p = 0.051), MCH (p = 0.000), and MCHC (p = 0.001) and Ret-He. Ret-He values of 33.7, 32.7, 32.4 and 28.6 pg were established as optimal cut-off values to identify functional ID, absolute ID, functional IDA, and absolute IDA, respectively.

Conclusion Ret-He is a reliable diagnostic tool for absolute and functional IDA in children with cancer.

Keywords

absolute ID - absolute IDA - childhood cancer - functional ID - functional IDA - hemoglobin - Ret-He

Patient Consent

Patient consent was obtained from every subject.

Publication History

Article published online:
21 March 2024

• References

• 1 Ludwig H, Van Belle S, Barrett-Lee P. et al. The European Cancer Anaemia Survey (ECAS): a large, multinational, prospective survey defining the prevalence, incidence, and treatment of anaemia in cancer patients. Eur J Cancer 2004; 40 (15) 2293-2306
• 2 Ludwig H, Müldür E, Endler G, Hübl W. Prevalence of iron deficiency across different tumors and its association with poor performance status, disease status and anemia. Ann Oncol 2013; 24 (07) 1886-1892
• 3 Abiri B, Vafa M. Iron deficiency and anemia in cancer patients: the role of iron treatment in anemic cancer patients. Nutr Cancer 2019; 0 (00) 1-9
• 4 Naoum FA. Iron deficiency in cancer patients. Rev Bras Hematol Hemoter 2016; 38 (04) 325-330
• 5 Uçar MA, Falay M, Dağdas S, Ceran F, Urlu SM, Özet G. The importance of RET-He in the diagnosis of iron deficiency and iron deficiency anemia and the evaluation of response to oral iron therapy. J Med Biochem 2019; 38 (04) 496-502
• 6 Baker RD, Greer FR, Bhatia JJS. et al; Committee on Nutrition American Academy of Pediatrics. Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0–3 years of age). Pediatrics 2010; 126 (05) 1040-1050
• 7 Peerschke EIB, Pessin MS, Maslak P. Using the hemoglobin content of reticulocytes (RET-He) to evaluate anemia in patients with cancer. Am J Clin Pathol 2014; 142 (04) 506-512
• 8 Elghetany MT, Schexneider KI. Erythrocytic disorder. In: McPherson RA, Pincus MR. ed. Henry's Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. Missouri:: Elsevier; 2017: 562
• 9 Toki Y, Ikuta K, Kawahara Y. et al. Reticulocyte hemoglobin equivalent as a potential marker for diagnosis of iron deficiency. Int J Hematol 2017; 106 (01) 116-125
• 10 Thomas L, Franck S, Messinger M, Linssen J, Thomé M, Thomas C. Reticulocyte hemoglobin measurement–comparison of two methods in the diagnosis of iron-restricted erythropoiesis. Clin Chem Lab Med 2005; 43 (11) 1193-1202
• 11 Brugnara C, Schiller B, Moran J. Reticulocyte hemoglobin equivalent (Ret He) and assessment of iron-deficient states. Clin Lab Haematol 2006; 28 (05) 303-308
• 12 Andriastuti M, Adiwidjaja M, Satari HI. Diagnosis of iron deficiency and iron deficiency anemia with reticulocyte hemoglobin content among children aged 6–18 years. Iran J Blood Cancer 2019; 11 (04) 127-132
• 13 Lorenz L, Arand J, Büchner K. et al. Reticulocyte haemoglobin content as a marker of iron deficiency. Arch Dis Child Fetal Neonatal Ed 2015; 100 (03) F198-F202
• 14 Rungngu SLP, Wahani A, Mantik MFJ. Reticulocyte hemoglobin equivalent for diagnosing iron deficiency anemia in children. Paediatr Indones 2016; 56 (02) 90
• 15 World Health Organization. Iron deficiency anaemia: assessment, prevention and control, a guide for program managers. Geneva: World Health Organization; 2001: 1-114
• 16 Aapro M, Beguin Y, Bokemeyer C. et al. Management of anaemia and iron deficiency in patients with cancer: ESMO Clinical Practice Guidelines. Ann Oncol 2018; 29 (February): 96-110
• 17 Andriastuti M, Ilmana G, Nawangwulan SA, Kosasih KA. Prevalence of anemia and iron profile among children and adolescent with low socio-economic status. Int J Pediatr Adolesc Med 2020; 7 (02) 88-92
• 18 Fan H, Su Y, Duan C. et al. Iron deficiency in children at the time of initial neuroblastoma diagnosis. Pediatr Investig 2019; 4 (01) 17-22
• 19 Hashemi SM, Mashhadi MA, Mohammadi M, Ebrahimi M, Allahyari A, Soleimanzadeh Mousavi SH. Absolute and functional iron deficiency anemia among different tumors in cancer patients in south part of Iran, 2014. Int J Hematol Oncol Stem Cell Res 2017; 11 (03) 192-198
• 20 Neoh K, Stanworth S, Pasricha SR, Bennett MI. Estimating prevalence of functional iron deficiency anaemia in advanced cancer. Support Care Cancer 2017; 25 (04) 1209-1214
• 21 Tantawy AA, Ragab IA, Ismail EA, Ebeid FSE, Al-Bshkar RM. Reticulocyte Hemoglobin Content (Ret He). J Pediatr Hematol Oncol 2020; 42 (03) e147-e151
• 22 Mateos ME, De-la-Cruz J, López-Laso E, Valdés MD, Nogales A. Reticulocyte hemoglobin content for the diagnosis of iron deficiency. J Pediatr Hematol Oncol 2008; 30 (07) 539-542
• 23 Brugnara C, Zurakowski D, DiCanzio J, Boyd T, Platt O. Reticulocyte hemoglobin content to diagnose iron deficiency in children. JAMA 1999; 281 (23) 2225-2230
• 24 Ullrich C, Wu A, Armsby C. et al. Screening healthy infants for iron deficiency using reticulocyte hemoglobin content. JAMA 2005; 294 (08) 924-930
• 25 Davidkova S, Prestidge TD, Reed PW, Kara T, Wong W, Prestidge C. Comparison of reticulocyte hemoglobin equivalent with traditional markers of iron and erythropoiesis in pediatric dialysis. Pediatr Nephrol 2016; 31 (05) 819-826
• 26 Di Pinto D, Paz M, Adragna M, López L. Clinical usefulness of the reticulocyte hemoglobin equivalent in children on hemodialysis. Arch Argent Pediatr 2020; 118 (06) 411-417
• 27 Syed S, Kugathasan S, Kumar A. et al. Use of reticulocyte hemoglobin content in the assessment of iron deficiency in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2017; 64 (05) 713-720
• 28 Chinudomwong P, Binyasing A, Trongsakul R, Paisooksantivatana K. Diagnostic performance of reticulocyte hemoglobin equivalent in assessing the iron status. J Clin Lab Anal 2020; 34 (06) e23225
• 29 Hönemann C, Hagemann O, Doll D, Luedi MML, Ruebsam ML, Meybohm P. [Reticulocyte hemoglobin equivalent as a diagnostic marker for the current iron deficiency: old wine in new bottles]. Anaesthesist 2020; 69 (12) 919-925