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Iron Metabolism & its Disorders
Optimizing diagnostic biomarkers of iron deficiency anemia in community-dwelling Indian women and preschool children
Ferrata Storti Foundation
Giridhar Kanuri,1,2 Deepti Chichula,1 Ritica Sawhney,1 Kevin Kuriakose,1 Sherwin De’Souza,1 Faye Pais,1 Karthika Arumugam1 and Arun S. Shet1,3
1Wellcome Trust- DBT Hematology Research Unit, St. Johns Research Institute, Bangalore, Karnataka, India; 2Department of Biotechnology, KLEF, Greenfields, Vaddeswaram, Andhra Pradesh, India and 3National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
ABSTRACT
The detection of iron deficiency anemia is challenged by the paucity of diagnostic tests demonstrating high sensitivity and specificity. Using two biomarkers, zinc-protoporphyrin/heme and hepcidin, we established the diagnostic cut-off values for iron deficiency anemia in preschool children and women. We randomly selected non-anemic individuals (n=190; women=90, children=100) and individuals with iron deficiency anemia (n=200; women=100, children=100) from a preexist- ing cohort of healthy preschool children and their mothers. The diagnos- tic performance of these biomarkers was estimated by analyzing receiv- er operating characteristic curves. Diagnostic cut-offs with a high predic- tive value for iron deficiency anemia were selected. Median zinc-proto- porphyrin/heme and hepcidin values in non-anemic children were 49 mmol/mol heme and 42 ng/mL, respectively, and in non-anemic women these values were 66 mmol/mol heme and 17.7ng/mL, respectively. Children and women with iron deficiency anemia had higher zinc-pro- toporphyrin/heme ratios (children=151 mmol/mol heme and women=155 mmol/mol heme) and lower hepcidin levels (children=1.2ng/mL and women=0.6ng/mL). A zinc-protoporphyrin/ heme ratio cut-off >90 mmole/mole heme in children and >107 mmole/mole heme in women was associated with a high diagnostic like- lihood for iron deficiency anemia (children, likelihood ratio=20.2: women, likelihood ratio=10.8). Hepcidin cut-off values of ≤6.8ng/mL in children and ≤4.5ng/mL in women were associated with a high diagnos- tic likelihood for iron deficiency anemia (children, likelihood ratio=14.3: women, likelihood ratio=16.2). The reference ranges and cut-off values identified in this study provide clinicians with guidance for applying these tests to detect iron deficiency anemia. Erythrocyte zinc-protopor- phyrin/heme ratio is a valid point-of-care biomarker to diagnose iron deficiency anemia.
Introduction
Iron deficiency anemia (IDA) is the leading cause of anemia worldwide1 with well established guidelines for diagnosis and treatment.2,3 Typically, the diagnosis of IDA is made when the plasma hemoglobin (Hb) falls below normal (<11.0g/dL in children and <12g/dL in women) and the serum ferritin is <12 mg/L.4 Unfortunately, the frequent coexistence of inflammation/infection confounds serum ferritin, which is an acute phase protein, mandating the performance of additional tests e.g., C-reactive protein (CRP) and serum transferrin receptor (sTfR). As a result, the diagnosis of IDA often requires a battery of diagnostic tests, trained technicians, and the use of expensive laboratory equipment, which increas- es costs and delays results. Clearly, developing biomarkers that quickly, easily and reliably detect IDA would be beneficial.
One such biomarker, zinc-protoporphyrin (ZPP), is formed in erythrocytes dur- ing iron-deficient erythropoiesis when the protoporphyrin ring incorporates an atom of zinc rather than iron. The ratio of zinc-protoporphyrin/heme (ZPP/H) can
Haematologica 2018 Volume 103(12):1991-1996
Correspondence:
arun.shet@nih.gov
Received: March 13, 2018. Accepted: August 6, 2018. Pre-published: August 9, 2018.
doi:10.3324/haematol.2018.193243
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/12/1991
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