New ferritin level threshold could improve iron deficiency diagnosis, say researchers

By Nicola Gordon-Seymour

- Last updated on GMT

Getty | NatchaS
Getty | NatchaS

Related tags Iron ferritin Research

Experts should consider a lower clinical threshold of ferritin levels when determining iron deficiency to ensure efficacy of early detection and relevant treatment, say researchers.

Following a retrospective study of 228 asymptomatic subjects, the authors suggest levels below 50ng/mL as the cut-off to reduce erroneous results and improve outcomes (as opposed to the current threshold range of less than 15ng/mL and up to 100ng/mL).

Furthermore, tests should be based on analysis of soluble transferrin receptor (sTfR) and hepcidin plasma biomarkers to simplify the process - and would constitute a less invasive and more accurate procedure than bone marrow biopsies.

“Both the heterogeneous distribution of iron stores in the bone marrow along with logistical problems regarding aspiration make this test not appropriate for routine examinations and contribute to the urgent search for alternative methods for iron deficiency diagnosis,” ​they write in Nutrients.

Clinical threshold

Iron is essential for red blood cell formation (erythropoiesis) and maintenance of whole-body cellular metabolism – and especially immune cell proliferation.

Ferropenia (iron deficiency) is a main cause of anaemia and can be the result of insufficient dietary intake, malabsorption, or chronic bleeding. Symptoms may be fatal and provoke chronic disease, such as colorectal cancer.

Deficiencies are usually treated with supplementation but there are no clear guidelines pertaining to the diagnosis. Global prevalence may be as high as 65% and therefore accurate early detection is crucial to formulate a diagnosis and treatment programme to prevent potential blood or hemoderivative transfusions, the authors say.

“Establishing a clinically relevant threshold for absolute ferropenia is exceptionally important since no consensus has been achieved up to now. In addition, it is considered that around 30% of the global population will develop ferropenia during their live, which is the main cause of anaemia.”

Hepcidin helps regulate iron metabolism and is related to ferritin levels, while the soluble sTfR receptor is a cleaved portion of the cellular receptor. Both are reliable plasma markers of iron status but are only used for research purposes and not in clinical settings, they explain.


The study involved assessment of outpatients involved in a Spanish iron metabolism study, as part of routine clinical management of blood analysis.

Subjects were 18 to 65 years old and clinically asymptomatic after blood analysis. Inclusion criteria included body mass index (BMI) of less than 40kg/m2​, no hospitalisation in the month prior to analysis, absence of chronic disease, and no recent iron or other supplementation.

Iron-related biomarkers, such as total iron, transferrin, and total sTfR, were measured using photometry, and ferritin with enhanced immunoturbidimetric assay analyses.

Associated biomarkers

Results conform with the findings from a previous study that also advised a set cut-off below 50ng/mL, where researchers noted “a close association between iron deposits in bone marrow aspirates and serum sTfR concentration​”, the authors say.

The current study demonstrated a strong correlation between sTfR to hepcidin ratios and ferritin levels and suggest “several forms of anaemia may benefit from therapies based on hepcidin-lowering agents or antagonists​”.

Researchers comment: “There has been much interest in the clinical significance of sTfR and hepcidin individually, as they are known as markers of iron deficiency, anaemia, chronic diseases and, more recently, both have been related to all-cause mortality regardless of anaemia and iron storage status.”

Sex-dependent ferropenia was identified in women and was caused by excessive menstrual bleeding and elevated iron requirements during pregnancy.

Obese patients were deemed more likely to suffer from deficiency due to increased circulating levels of acute-phase reactant hepcidin and adipose inflammation.

Routine analysis

Based on findings, the authors stress the importance of establishing “a clinically relevant threshold​” for absolute ferropenia since there is currently no consensus.

They maintain that future predictions for iron deficiency are considerably higher when based on the proposed assessment method and indicate underdiagnosis of ferropenia within the general population and “consequent underestimation of possible underlying related pathologies​”.

As such, the authors strongly advocate routine blood analysis for iron metabolism determinations, including hepcidin and sTfR markers, “to promptly detect iron deficiency requiring further investigation and treatment”​ and ensure result accuracy.

Source: Nutrients

Published online, November 10, 2022:

‘Threshold Ferritin Concentrations Reflecting Early Iron Deficiency Based on Hepcidin and Soluble Transferrin Receptor Serum Levels in Patients with Absolute Iron Deficiency’

Authors : Laura Tarancon-Diez, Miguel Genebat, Manuela Roman-Enry, Elena Vázquez-Alejo, Maria de la Sierra Espinar-Buitrago, Manuel Leal and M Ángeles Muñoz-Fernandez

Related topics Research Minerals

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