Preliminary investigation of serum ferritin level and its reference interval in apparent healthy children population in Provincial Children’s Hospital

Introduction

Ferritin is a biomarker of physiological iron stores, the determination of serum ferritin can reflect the total iron storage in the body and can be used as a reliable index for the diagnosis of iron deficiency or overload [1]. Under normal circumstances, there is a small amount of ferritin in peripheral blood, which is called serum ferritin (SF). As an acute phase reactant, SF has been found to be elevated in patient by various non overload conditions including inflammation, infectious diseases, liver disease, malignancies, and hepatocellular carcinoma [2]. Therefore, ferritin can be used not only function as a marker of iron reserves, but may also to aid in clinical decision-making, including prognosis, diagnosis, treatment, and/or patient management [3]. As a result, the number of ferritin detection increased rapidly year by year.

Analyte reference interval (RIS) is one of the most widely used clinical decision making tools as the basis for interpreting medical laboratory data [4]. However, although in clinical practice measurement of SF has largely replaced laboratory assays of serum iron and transferrin or total iron‐binding capacity, there is no gold standard method for measuring SF. In contrast to the specificity of low ferritin concentrations for iron deficiency, less ferritin elevation is caused by iron overload rather than by non-overload. Therefore, any increase in ferritin above the reference interval (RI) could lead to follow-up such as additional laboratory testing and imaging, to identify the source [5]. This makes it difficult for doctors to interpret the results. Furthermore, studies have shown that there are significant ethnic differences in SF levels [5, 6]. Therefore, it is necessary to establish your own RIs based on its population and analytical methods for use in clinical laboratories.

This study retrospectively analyzed the ferritin results of the physical examination population in Zhejiang Grade Children’s Hospital in 2020, and established a reference range of ferritin applicable to the population in this region, so as to provide more accurate and reliable diagnostic data for the clinic.

Materials and methods

Results

SF value in general

Figure 1 shows the relationship between age and SF levels. Figure 1A represents male and Figure 1B represents female (Figure 1). There was no significant difference in SF between men and women (p=0.244).We found that most of the subjects were distributed within the range of 20.1–40.0, followed by 40.1–60.0 groups.

Figure 1:

Correlation between age and serum ferritin levels.

(A) Males; (B) females.

Discussion

As an important iron storage substance in human body, the increase or decrease of serum ferric protein is of great value in evaluating normal tissue metabolism or assisting diagnosis of certain diseases [8]. Decreased SF is common in iron deficiency anemia, massive blood loss, long-term diarrhea, malnutrition and so on [9]. SF increased significantly in megaloblastic anemia, aplastic anemia and acute hematopoietic stagnation, and returned to normal when the condition improved [9]. Recent studies have shown that the increase of SF can assist in the diagnosis of malignant tumors [9]. The increase of SF in tumor patients was highest in liver cancer patients, followed by lung cancer patients, leukemia patients and malignant lymphoma patients [10]. SF is higher when the tumor metastases. Combined detection of tumor markers and ferritin will improve the detection rate of tumor diseases [11]. In summary, serum ferric protein has become a commonly used clinical test item due to its role in disease surveillance and screening.

In our study, we found that after the age of 3, with the increase of age, ferric protein will gradually increase. Studies have shown that with age [12], degenerative changes occur in liver, spleen, bone marrow and systemic reticuloendothelial cells. Iron-containing tissues are activated, disintegrate and release ferric protein. It has been reported in many literatures [13] that adult male serum ferric protein level is significantly higher than that of female, so it is necessary to set the reference interval according to gender group. The results showed that the SF level in both men and women showed a trend of increasing with age, but there was no significant difference in the average ferritin level in men and women. The samples of our study are from patients undergoing physical examination, and after reviewing the literature, newborns rarely take part in physical examination, at least there are no participants in our study. So there is no description of newborns in our study. In addition, according to the requirements of hospital physical examination, some items of menstruation can not be examined, so the examination is generally in the state of non-menstrual period, which should have no effect on the detection value of ferritin. Different manufacturers of kits due to different methodologies, the reference interval difference is obvious; Different regions, different ethnic groups of normal ferritin level also has the obvious difference [14], so the reference interval must consider regional differences in information and the crowd, direct reference to the manufacturer instructions or the literature of ferritin reference range will not be able to objectively reflect the reality of the local population ferritin level, so the suggestion in the evaluation of SF reference interval must be grouped according to age, sex, sets up.

Based on the statistics of children’s SF in the third class hospital of Zhejiang Province, a ferritin reference model that may be applicable to Zhejiang Province is established. The SF levels of the apparent healthy people in Provincial Children’s Hospital area were slightly different among people of different genders and ages. Test interval (but it should be noted that this statistics is only applicable to Beckman Kurt automatic chemiluminescence immunoanalyzer), which is helpful for clinical more objective disease diagnosis and monitoring, also provides a basis for physical examination people to correctly evaluate their ferritin level, avoid excessive panic caused by false high ferritin, and help clinicians make more standardized iron supplementation, prevent iron overload disease.