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Total Iron Binding Capacity and Transferrin Concentration in the Assessment of Iron Status

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Abstract

Transferrin concentration and total iron binding capacity (TIBC) are currently used to assess iron status. Although correlation between TIBC and transferrin is generally considered as good, conversion factors between the two analytes found in literature show large differences. Although the price per test is lower for TIBC, there are a number of analytical advantages of serum transferrin. Due to binding of iron to other plasma proteins (mainly albumin), TIBC methods generally overestimate the iron binding capacity of transferrin. Moreover, no generic reference values are available for TIBC. In contrast to TIBC, internationally accepted interim reference ranges are available for serum transferrin. The introduction of the international CRM 470 protein standard material has lead to a significant reduction in interlaboratory variation for transferring measurements. In view of these observations, determination of transferrin concentration, rather than TIBC, is recommended. However, in non-European populations characterized by a marked genetic variation in transferrin (TF BC and TF CD variants), in certain cases, immunochemical determination of transferrin may lead to errors. In these populations, TIBC measurements may be preferred.
Clin Chem Lab Med 2002; 40(10):10141018 © 2002 by Walter de Gruyter · Berlin · New York
Ishmael Kasvosve
1
and Joris Delanghe
2
*
1
Department of Chemical Pathology, University of Zimbabwe
Medical School, Harare, Zimbabwe
2
Department of Clinical Chemistry, Ghent University, Gent,
Belgium
Transferrin concentration and total iron binding capac-
ity (TIBC) are currently used to assess iron status. Al-
though correlation between TIBC and transferrin is
generally considered as good, conversion factors be-
tween the two analytes found in literature show large
differences.
Although the price per test is lower for TIBC, there
are a number of analytical advantages of serum trans-
ferrin. Due to binding of iron to other plasma proteins
(mainly albumin), TIBC methods generally overesti-
mate the iron binding capacity of transferrin. More-
over, no generic reference values are available for
TIBC. In contrast to TIBC, internationally accepted in-
terim reference ranges are available for serum trans-
ferrin. The introduction of the international CRM 470
protein standard material has lead to a significant re-
duction in interlaboratory variation for transferring
measurements. In view of these observations, deter-
mination of transferrin concentration, rather than
TIBC, is recommended. However, in non-European
populations characterized by a marked genetic varia-
tion in transferrin (TF BC and TF CD variants), in certain
cases, immunochemical determination of transferrin
may lead to errors. In these populations, TIBC mea-
surements may be preferred. Clin Chem Lab Med 2002;
40(10):10141018
Key words: Hemochromatosis; Iron; Iron overload; To-
tal iron binding capacity; Transferrin.
Abbreviations: CRM, certified reference material; SNP,
single nucleotide polymorphism; TF, transferrin; TIBC,
total iron binding capacity; UIBC, unsaturated iron-
binding capacity.
Introduction
Both iron deficiency and iron overload are important
public health problems. Iron deficiency is the most
prevalent nutritional problem in the world today, and
as much as 500 million people may be affected (1). On
the other hand, the presence of increased iron stores
with associated organ damage is also common. In peo-
ple of European descent, hereditary hemochromatosis
is the most prevalent monoallelic genetic disease (2)
and the utility of screening the general population is
being examined (3). In Africans, iron overload affects
up to 10% of some rural populations (4, 5).
Several laboratory tests are presently available for
the assessment of iron status (6, 7). The description by
Ramsay in 1957 of a practical way of determining the
total iron binding capacity (TIBC) of serum or plasma
provided a diagnostic test for both iron deficiency and
iron overload (8). Since then, TIBC has been used as a
parameter to assess the maximal capacity of serum to
transport iron. Since under physiological conditions
iron is exclusively bound by the β-globulin transferrin
(TF), determination of TF concentration in serum offers
a newer alternative for assessing the TF binding capac-
ity. The combination of total serum iron and either TIBC
or TF measurements allows the calculation of the occu-
pied and available TF binding sites.
TF saturation (calculated as a ratio of iron concentra-
tion and TIBC multiplied by 100), together with serum
ferritin are reliable screening tests for iron overload (9,
10). TF concentration has been used to derive TIBC and,
indirectly, TF saturation (11). TF index calculated as
serum iron divided by TF concentration has been sug-
gested as a better alternative to saturation in screening
for iron overload (12).
Both TIBC and TF assays have improved consider-
ably in the last decades (Table 1). In this review article
we discuss the advantages and disadvantages of the
use of TIBC and serum TF in the assessment of iron sta-
tus. We also address the implications of the genetic
variation of TF on the usefulness of these tests (13).
Iron Binding Capacity
In the plasma, iron is predominantly bound to TF, and
TIBC depends on the concentration of this globulin.
The fraction of TF to which iron is not actually bound is
known as the “unsaturated iron-binding capacity”
(UIBC). The sum of serum iron concentration and the
UIBC gives the TIBC.
Estimation of Unsaturated Iron-Binding Capacity
UIBC may be deduced from TIBC and serum iron con-
centration or measured directly by an isotope method.
In the latter method, the amount of radioactive iron re-
*E-mail of the corresponding author:
joris.delanghe@rug.ac.be
Review
Total Iron Binding Capacity and Transferrin Concentration
in the Assessment of Iron Status
Kasvosve and Delanghe: Iron binding capacity, transferrin and iron status 1015
quired to saturate the serum (i.e. the UIBC) is measured
directly. In the original method of Bothwell et al.,
59
Fe-
ammonium citrate was used and the absorption car-
ried out on Amberlite resin (14).
Total Iron Binding Capacity Determination
The method for TIBC measurement was first described
by Ramsay (8) and later refined by the International
Committee for Standardisation in Haematology and
described as a recommended procedure (15). This was
revised in 1990 (16). The chemical measurement of
TIBC consists of three steps. The first step involves ad-
dition of supraphysiological amounts of FeCl
3
to satu-
rate the free binding sites on TF; the second is the re-
moval of unbound excess iron by adsorption onto solid
magnesium carbonate (8), charcoal or an ion-exchange
resin (17); the third is the determination of iron that is
dissociated from TF at acidic pH. Recently, direct TIBC
assays have been described (18, 19). The addition of
excess amounts of FeCl
3
results in nonspecific binding
of iron to albumin and other plasma proteins, leading
to overestimation of TIBC especially at low TF concen-
trations, as seen, for instance, in liver disease and in
nephrotic syndrome (20).
One of the major drawbacks of the TIBC test is the
large variation: reference ranges differ by as much as
35% between commercial methods (11), therefore a
generic reference interval can no longer be stated. Ex-
isting UIBC-based methods generally exhibit a signifi-
cant negative bias compared with TIBC methods (21).
Furthermore, the chemical methods for TIBC require a
relatively large sample volume and are sensitive to
contamination of the laboratory ware with iron (22).
Serum Transferrin Determination
Immunological methods for the measurement of
serum TF concentration are now available. The earlier
immunodiffusion methods (23) have been largely re-
placed by either automated immunoturbidimetric (24)
or immunonephelometric procedures (25). Although
the cost per test is lower for TIBC, determination of
serum TF offers some technical advantages. In addi-
tion, the sample volume needed for analysis of TF is
smaller.
Recently, CRM 470 standardization was adopted for
fourteen plasma proteins (26). For TF, the reference
range was reported to be 2.03.6 g/l. Recently, refer-
ence intervals were determined in a Japanese popula-
tion using the same standardization (27). The results
obtained were more or less similar (1.903.20 g/l),
suggesting that racial differences are not very pro-
nounced. The introduction of the international refer-
ence material for serum proteins has resulted in a sig-
nificant reduction of the between-laboratory variance
for TF (28).
Coefficients of variation are very low, and well below
the requirements based on the large biological varia-
tion of iron (29). International interim reference ranges
have been proposed for a number of plasma proteins,
including TF (30) which have been accepted by the In-
ternational Federation of Clinical Chemistry and Labo-
ratory Medicine (IFCC) and many national scientific so-
cieties.
Molecular Variation of TF
Like many other plasma proteins, TF is characterized
by genetically determined polymorphism. In Cau-
casians, individuals are homozygous for TF CC (C=
common). In less than 1% of Caucasians, TF CD (catho-
dal variants) and TF BC (anodal variants) heterozygotes
are found. In African and indigenous populations of
Oceania, prevalence of TF variants is often higher than
10% (31).
Isoelectric focusing of TF allows for further possibili-
ties to distinguish between TF CC subtypes. Recently,
single nucleotide polymorphisms (SNP) in the TF 5’
flanking region have been associated with differences
in TIBC. In patients with Parkinson’s disease, a disorder
in which there is abnormal iron deposition in the brain,
the presence of TF haplotype 3 was in slight excess
over the normal population (32). In cases of problems
of interpretation of TF results, the possibility of a TF
variant might be considered. In such situations the de-
termination of TIBC by chemical methods better re-
flects the patient’s iron status. The heterogeneity of the
carbohydrate moiety of TF is probably of no impor-
tance for the determination of serum TF. No correlation
has been found between the relative amount of carbo-
hydrate-deficient TF and the total TF concentration
(33).
Table 1 Milestones in total iron binding capacity and transferrin assays.
Year Milestone Reference
1957 TIBC determination 8
1959 Determination of UIBC using radioactive iron 14
1965 Radial immunodiffusion technique for transferrin measurement 23
1976 Immunoturbidimetric assay for serum transferrin 24
1978 Immunonephelometric assay for serum transferrin 25
1994 CRM 470 standard for 14 plasma proteins (including transferrin) 26
1996 Interim reference values based on CRM 470 standard 30
1016 Kasvosve and Delanghe: Iron binding capacity, transferrin and iron status
Derivation of TIBC from Serum TF Concentration
Since 1 mol of TF (molecular mass 79 570 Da) has the
capacity to bind two atoms of iron (atomic mass 56),
formulas for calculating TF saturation from TIBC and
vice versa have been proposed. Serum TF concentra-
tion may be estimated from TIBC by the following rela-
tionships:
Serum TF (g/l) = 0.007 × TIBC (µg/l) (11).
TIBC (µg/dl) = TF (mg/dl) × 1.41
TIBC (µmol/l) = TF (g/l) × 25.2
TF saturation (%):
Serum iron (µg/dl)/TF (mg/dl) × 70.9
Serum iron (µmol/l)/TF (mg/dl) × 398 (34).
The above mathematical derivations have weaknesses.
Because some of the iron is bound to other proteins
(especially albumin) (35, 36) the relation between
serum TF concentration and TIBC is not completely lin-
ear. Due to binding to other plasma proteins, the calcu-
lated TIBC values are a few micromoles per liter higher
than the TF-bound iron. In the elderly, iron binding ca-
pacity correlated with serum albumin (35). Moreover,
change in calibrator yields TF concentrations that are
13% lower than those obtained with the older calibra-
tor (21). While early estimates suggested a value of
90000 Da as the molecular mass of TF (20, 37), more re-
cent estimate based on the amino acid sequence gives
a calculated molecular mass of 79570 Da (34, 38). Be-
cause of uncertainty as to the molecular mass of TF,
various values for TF molecular mass are being used
resulting in different conversion factors applied by
different laboratories (12). Therefore, a number of ma-
nufacturers recommend that the experimentally deter-
mined factor of 1.27 be applied instead of the theore-
tically derived 1.41 (39). This can be regarded as a
mathematical compensation for the non-TF bound
iron.
Several articles suggest that, contrary to the theory,
the relation between TIBC and TF is not fixed, espe-
cially when results are outside the reference range (40,
41). The reported mean ratio between TIBC and TF has
ranged from a low of 11.3 to a high of 26.1 (21). As a
consequence, the development of a universal algorithm
for the conversion of TF values into TIBC is not possible
(39).
Diagnostic Use
A body of evidence exists supporting the hypothesis
that screening for hereditary hemochromatosis may be
cost-effective, given the low-cost, low-risk therapeutic
options available for the affected individuals (42). It is
crucial to diagnose hemochromatosis before irre-
versible organ damage (hepatic cirrhosis, diabetes) de-
velops. A DNA-based test for the HFE gene is now
available but it is only useful for the detection of he-
mochromatosis in the family members of patients with
a proven case of the disease (3). The protocol for
screening for hemochromatois entails determination
of serum TF saturation and serum ferritin level (3). In
contrast to iron deficiency, in which the diagnostic sen-
sitivity of serum ferritin is superior to TF saturation, TF
saturation has the highest predictive value in screening
for hereditary hemochromatosis (39). Elevation in
serum TF saturation occurs before significant iron
loading.
Persistently elevated TF saturation is the earliest bio-
chemical evidence of hemochromatosis. Fasting TF
saturation 45% is used as the screening threshold be-
cause it identifies 98% of affected persons while pro-
ducing relatively few false-positive results (3, 43). Since
TF saturation is obtained by dividing serum iron con-
centration by TIBC and expressing it as a percentage,
the determination of TIBC is necessary to compute TF
saturation. It is clear that the cost-effectiveness of he-
mochromatosis screening programmes will partly de-
pend on the method and the standardization of deter-
mining TF saturation.
Use of TIBC may be more problematic in cases of
atransferrinemia. Congenital atransferrinemia is a rare
genetic condition characterized by the absence of TF. In
these cases, extremely low values or even complete
absence of serum TF are found. Acquired atransfer-
rinemia has been described in association with the
nephrotic syndrome probably due to loss of TF through
the kidney (20, 44, 45). One patient with functional dis-
order of TF due to the presence of TF-IgG-TF immune
complexes has been described (46). In such patients,
positive values for TIBC (up to 69 µg/dl) have been re-
ported despite TF concentration readings of 0 mg/dl
(47, 48). This paradoxical finding could be attributed to
the increased nonspecific binding of iron to other
plasma proteins. Indeed, when TF is more than 50%
saturated, some of the iron is bound to other plasma
proteins (25).
Conclusions
There are no generic reference values available for
TIBC. Intralaboratory variation increases due to varia-
tion of the TIBC method. In contrast, the introduction
of automated immunoassays and the universal CRM
470 protein standard has led to acceptable interlabo-
ratory variation for serum TF concentration. Gener-
ally, TF determinations have several analytical advan-
tages compared to TIBC determinations. Because the
TF assay is more precise, more readily automated
either by immunoturbidimetry or immunonephelome-
try, and less labor-intensive than the TIBC method,
many laboratories are now measuring TF rather than
TIBC. However, in certain cases attention should be
paid to the consequences of genetically controlled
polymorphisms of TF, especially in non-European
populations. In case of discordant laboratory findings
in the assessment of iron status due to the TF variants,
non-immunological determination of TF (e.g. by capil-
lary electrophoresis) (13) or chemical measurement of
TIBC is preferred.
Kasvosve and Delanghe: Iron binding capacity, transferrin and iron status 1017
Acknowledgements
This work was supported in part by an IFCC Scientific Ex-
change Fellowship Programme 13.5.15, 1999. We thank Erna
Vanbekbergen and Freddy Lason for their kind support during
the preparation of this manuscript.
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Received 25 June 2002, revised 30 August 2002,
accepted 9 September 2002
Corresponding author: Prof. J.R. Delanghe,
Department of Clinical Chemistry, Ghent University,
185 De Pintelaan, 9000 Gent, Belgium
Phone: + 32 9 2402956, Fax: + 32 9 2404985
E-mail: joris.delanghe@rug.ac.be
... Serum ferritin was determined using an electrochemiluminescence immunoassay using a Cobas e601 module (Roche). Assuming that 1 mol of transferrin (molecular mass 79,570 Da) has the capacity to bind two atoms of iron (atomic mass 56), transferrin saturation (TSAT) was calculated as [31]: ...
... Total iron binding capacity (TIBC) was calculated as: [31] TIBC = (μg/dL) = Transferrin (mg/dL) × 1.41 ...
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... Serum iron is primarily iron bound to transferrin in serum and is considered a marker of iron levels in the circulatory system. TIBC is the maximum amount of iron that can be bound by transferrin per liter of serum, which actually reflects the level of transferrin (37)(38)(39). Numerous studies have revealed that the total serum iron-binding capacity increased and serum iron and serum ferritin levels decreased when iron deficiency occurred in the body, and these indicators can be increased or decreased accordingly after iron supplementation (10,40). Similarly, in the current study, dietary FGC supplementation attenuated the level of serum iron and decreased the level of TIBC, which indicated that FGC supplementation contributes to the transport and absorption of iron in piglets. ...
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The present research aimed to explore the effect of dietary ferrous glycine chelate supplementation on performance, serum immune-antioxidant parameters, fecal volatile fatty acids, and microbiota in weaned piglets. A total of 80 healthy piglets (weaned at 28 day with an initial weight of 7.43 ± 1.51 kg) were separated into two treatments with five replicates of eight pigs each following a completely randomized block design. The diet was a corn-soybean basal diet with 2,000 mg/kg ferrous glycine chelates (FGC) or not (Ctrl). The serum and fecal samples were collected on days 14 and 28 of the experiment. The results indicated that dietary FGC supplementation improved (p < 0.05) the average daily gain and average daily feed intake overall, alleviated (p < 0.05) the diarrhea rate of piglets at the early stage, enhanced (p < 0.05) the levels of superoxide dismutase and catalase on day 14 and lowered (p < 0.05) the MDA level overall. Similarly, the levels of growth hormone and serum iron were increased (p < 0.05) in the FGC group. Moreover, dietary FGC supplementation was capable of modulating the microbial community structure of piglets in the early period, increasing (p < 0.05) the abundance of short-chain fatty acid-producing bacteria Tezzerella, decreasing (p < 0.05) the abundance of potentially pathogenic bacteria Slackia, Olsenella, and Prevotella as well as stimulating (p < 0.05) the propanoate and butanoate metabolisms. Briefly, dietary supplemented FGC ameliorates the performance and alleviated the diarrhea of piglets by enhancing antioxidant properties, improving iron transport, up-regulating the growth hormone, modulating the fecal microbiota, and increasing the metabolism function. Therefore, FGC is effective for early iron supplementation and growth of piglets and may be more effective in neonatal piglets.
... It is done by drawing blood and measuring the maximum quantity of iron that it can carry, which indirectly measures transferrin (Yamanishi et al., 2003) since transferrin is the most active carrier. TIBC is cheaper than a direct measurement of transferrin (Kasvosve et al., 2002). The TIBC should not be muddled with the UIBC, or "unsaturated iron binding capacity ". ...
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Background: Hepcidin, a peptide hormone composed of 25 amino acids. Hepcidin is synthesized mainly in the liver. Iron deficiency anemia (IDA) is common during pregnancy and is associated with higher maternal morbidity and mortality in Gaza strip. Understanding of hepcidin hormone and its role in iron metabolism could lead to new indicators for earlier detection of cases with IDA. Objective: To assess hepcidin status among IDA pregnant women and its relationship with some biochemical variables in Gaza strip. Materials and methods: A case control study this study comprised 45 IDA pregnant women and 45 healthy pregnant women. Questionnaire interviews were applied among the study population. Serum hepcidin and ferritin were measured by ELISA, iron and TIBC were determined photometrically. Complete blood count (CBC) was also performed. Transferrin and transferrin saturation were calculated. An approval was obtained from local ethical committee to conduct this study. Overall data were computer analyzed using SPSS. Results: The mean level of serum hepcidin, iron, transferrin saturation, and ferritin in cases were significantly lower than that in controls (2.6±4 ng/ml, 63.2±25.3 µg/dl, 15.6±8.0% and 8.0±9.7 ng/ml versus 7.5±7.3 ng/ml, 77.7±22.9 µg/dl, 23.5±8.0% and 15.4±14.3 ng/ml respectively with p=0.000). The Pearson correlation test showed positive significant correlations between hepcidin levels and serum iron, ferritin, and transferrin saturation (r=0.547, p=0.000; r=0.558, p=0.000 & r=0.577, p=0.000 respectively). On the other hand, negative correlations were showed with TIBC and transferrin (r=-0.551, p=0.000 & r=-0.526, p=0.000) respectively. The average values of RBC, Hb, HCT, MCV, MCH, and MCHC were significantly lower among IDA pregnant women (3.3±2.4, 9.7±0.8, 29.4±2.3, 76.6±4.8, 25.6±2.2 & 33.2±1.5 respectively) compared to controls (4.0±0.3, 11.8±0.6, 34.7±2.0, 86.3±3.3, 29.4±1.3 & 34±0.9; p=0.000) respectively. RDW was significantly higher in cases vs. controls (16.6±2.4, 13.7±0.6; p=0.000). Conclusions: Hepcidin hormone was lower in IDA pregnant women than healthy pregnant women. Thus it is recommended to carry out further studies to evaluate the role of hepcidin in the diagnosis of IDA among different gestational women.
... The transferrin saturation (TS%) was calculated by the equation shown below [31]. ...
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Red and processed meat consumption and obesity are established risk factors for colorectal adenoma (CRA). Adverse changes in biomarkers of body iron stores (total serum iron, ferritin, transferrin and transferrin saturation), inflammation (high-sensitivity C-reactive protein [hs-CRP]) and anti-oxidative capacity (total of thiol groups (-S-H) of proteins [SHP]) might reflect underlying mechanisms that could explain the association of red/processed meat consumption and obesity with CRA. Overall, 100 CRA cases (including 71 advanced cases) and 100 CRA-free controls were frequency-matched on age and sex and were selected from a colonoscopy screening cohort. Odds ratios (OR) and 95% confidence intervals (95%CI) for comparisons of top and bottom biomarker tertiles were derived from multivariable logistic regression models. Ferritin levels were significantly positively associated with red/processed meat consumption and hs-CRP levels with obesity. SHP levels were significantly inversely associated with obesity. Transferrin saturation was strongly positively associated with overall and advanced CRA (ORs [95%CIs]: 3.05 [1.30–7.19] and 2.71 [1.03–7.13], respectively). Due to the high correlation with transferrin saturation, results for total serum iron concentration were similar (but not statistically significant). Furthermore, SHP concentration was significantly inversely associated with advanced CRA (OR [95%CI]: 0.29 [0.10–0.84]) but not with overall CRA (OR [95%CI]: 0.65 [0.27–1.56]). Ferritin, transferrin, and hs-CRP levels were not associated with CRA. Conclusions: High transferrin saturation as a sign of iron overload and a low SHP concentration as a sign of redox imbalance in obese patients might reflect underlying mechanisms that could in part explain the associations of iron overload and obesity with CRA.
... Variables having substantial loadings were markers of inflammation (CRP and ESR), clinical activity (DAS28), another subset of iron metabolism (TIBC and FER), and finally HEP. Given that TIBC actually reflects transferrin levels, 41,42 both TIBC and FER are also considered acute phase protein along with CRP. 43,44 In fact TIBC as a surrogate of transferrin had a strong negative loading on factor 2, while FER and CRP had a positive loading that demonstrates their role as "negative" and "positive" acute phase protein, respectively. ...
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Objective: Anemia of chronic disease is a frequent consequence in rheumatoid arthritis and is associated with major clinical and patient outcomes. The present cross-sectional study explored the role of hepcidin (HEP) in anemia of chronic disease in rheumatoid arthritis by studying its relationships with markers of anemia, iron metabolism, inflammation, and erythropoiesis. Methods: Blood samples from anemic (n = 43) and nonanemic (n = 43) rheumatoid arthritis patients were analyzed for markers of anemia (hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red cells distribution width, and reticulocyte hemoglobin), iron metabolism (iron, total iron binding capacity, ferritin, transferrin saturation, soluble transferrin receptor), inflammation (erythrocyte sedimentation rate, C-reactive protein, and interleukin 6), and erythropoiesis (erythropoietin and HEP). Correlation analysis was used to identify relationships between HEP and all other variables. Principal component analysis was used to identify common underlying dimensions representing linear combinations of all variables. Results: HEP had statistically significant mostly moderate-to-large correlations with markers of anemia (0.30–0.70, all p < 0.01), small correlation with markers of iron metabolism and markers of inflammation (r = 0.20–0.40, all p < 0.01), and moderate correlations with markers of erythropoiesis. Principal component analysis revealed two underlying components (factors) capturing approximately 50% of total variability. Factor 1 comprised mainly of markers of anemia, iron metabolism, and erythropoiesis and was related to “erythrocyte health status,” while factor 2 comprised mainly markers of inflammation and iron metabolism and was related to “acute phase reactants.” HEP was the only variable demonstrating substantial loadings on both factors. Conclusions: HEP is related to markers of anemia, iron metabolism, inflammation, and erythropoiesis. In addition, when all variables are “reduced” to a minimum number of two “latent” factors, HEP is loaded on both, thus underlying its pivotal role in the complex interaction of the erythropoietic response in inflammation-induced anemia and/or functional iron deficiency.
... TIBC findings in our study can be explained by that TIBC is low in anemia of chronic disease because there is excess iron, but it is not easily available. While, in iron-deficiency anemia, the TIBC is being elevated (higher than 400-450 mcg/dL) because iron stores are low (19) . ...
... Although correlation between TIBC and transferrin is generally good, the reported conversion factors between the two analytes show large differences. Because iron binds to other plasma proteins (mainly albumin), TIBC methods generally overestimate transferrin iron-binding capacity [41]. We found that only the lowest TIBC quartile was associated with ESRD. ...
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Background: To investigate the relationship between serum iron status and renal outcome in patients with type 2 diabetes mellitus (T2DM). Methods: Chinese patients (n=111) with T2DM and biopsy-proven diabetic nephropathy (DN) were surveyed in a longitudinal, retrospective study. Serum iron, total iron-binding capacity, ferritin, and transferrin were measured at the time of renal biopsy. Iron deposition and transferrin staining were performed with renal biopsy specimens of DN patients and potential kidney donors. End-stage renal disease (ESRD) was the end-point. ESRD was defined as an estimated glomerular filtration rate <15 mL/min/1.73 m2 or the need for chronic renal replacement therapy. Cox proportional hazard models were used to estimate the hazard ratios (HRs) for the influence of serum iron metabolism on ESRD. Results: During a median follow up of 30.9 months, 66 (59.5%) patients progressed to ESRD. After adjusting for age, sex, baseline systolic blood pressure, renal functions, hemoglobin, HbA1c, and pathological findings, lower serum transferrin concentrations were significantly associated with higher ESRD in multivariate models. Compared with patients in the highest transferrin quartile (≥1.65 g/L), patients in the lowest quartile (≤1.15 g/L) had multivariable-adjusted HR (95% confidence interval) of 7.36 (1.40-38.65) for ESRD. Moreover, tubular epithelial cells in DN exhibited a higher deposition of iron and transferrin expression compared with healthy controls. Conclusions: Low serum transferrin concentration was associated with diabetic ESRD in patients with T2DM. Free iron nephrotoxicity and poor nutritional status with accumulated iron or transferrin deposition might contribute to ESRD.
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Gynecological neoplasms pose a serious threat to women’s health. It is estimated that in 2020, there were nearly 1.3 million new cases worldwide, from which almost 50% ended in death. The most commonly diagnosed are cervical and endometrial cancers; when it comes to infertility, it affects ~48.5 million couples worldwide and the number is continually rising. Ageing of the population, environmental factors such as dietary habits, environmental pollutants and increasing prevalence of risk factors may affect the reproductive potential in women. Therefore, in order to identify potential risk factors for these issues, attention has been drawn to trace elements. Trace mineral imbalances can be caused by a variety of causes, starting with hereditary diseases, finishing with an incorrect diet or exposure to polluted air or water. In this review, we aimed to summarize the current knowledge regarding trace elements imbalances in the case of gynecologic cancers as well as female fertility and during pregnancy.
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An inter-laboratory investigation into the assay of serum iron binding capacity by the magnesium carbonate adsorption method was undertaken. The source of MgCO 3, storage temperature of whole serum, lyophilization and storage temperature of lyophilized serum were identified as sources of inter-laboratory variation. Protocols for the clinical assay of UIBC and TIBC are given which have achieved satisfactory inter-laboratory precision.
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Certain modifications to the previously published ICSH recommendations (1978) have been approved by the Iron Panel of the International Committee for Standardization in Haematology (ICSH). They include substitution of the chromogen bathophenanthroline sulphonate with ferrozine or ferene, which are more sensitive and cheaper, and a reduction in the volume of the test sample from 2 ml to 0.5 ml.
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1.1. The transferrin content in normal human sera is in general 20% lower than should be expected from the total iron-binding capacity.2.2. At saturation degrees higher than 50%, iron is distributed over serum prot eins in addition to transferrin.3.3. The addition of HCO3−, ascorbic acid, differences in time or temperature have no influence on the binding of iron to transferrin at saturation degrees between 60–100%.4.4. The immunochemical determination of transferrin is simple, reliable and specific. We prefer this method to the determination of the total iron binding capacity.
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Iron has the capacity to accept and donate electrons readily, interconverting between ferric (Fe2+) and ferrous (Fe3+) forms. This capability makes it a useful component of cytochromes, oxygen-binding molecules (i.e., hemoglobin and myoglobin), and many enzymes. However, iron can also damage tissues by catalyzing the conversion of hydrogen peroxide to free-radical ions that attack cellular membranes, proteins, and DNA. Proteins sequester iron to reduce this threat. Iron ions circulate bound to plasma transferrin and accumulate within cells in the form of ferritin. Iron protoporphyrin (heme) and iron–sulfur clusters serve as enzyme cofactors. Under normal circumstances, only trace amounts . . .
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Radiometric, colorimetric, and two immunochemical methods for measuring total iron-binding capacity are compared. We evaluated the procedures on the basis of precision, applicability to a pediatric population, and accuracy as assessed by analytical recovery of purified transferrin. The immunoephelometric assay for transferrin provides significant advantages over the other methods examined.
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Immunologically determined reference values of serum transferrin are presented for adults and children. A good correlation between serum transferrin and total iron-binding capacity values was found. In 2 groups of anaemic patients - 51 patients with iron deficiency anaemia and 45 patients with anaemia of chronic disorders - serum transferrin determination distinguishes the two groups of anaemic patients from normals somewhat better than TIBC determination.
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A 71-year-old woman showed a highly unusual pattern of iron distribution in the organism which was associated with iron overload. The hallmark of this disease was an extreme hypersiderinemia, the serum iron reaching about 800 mug/100 ml. There was a pigment cirrhosis of the liver, bronzed skin containing hemosiderin, and diabetes mellitus. Paradoxically, hemosiderin was not detectable in bone marrow macrophages, sideroblasts and erythrocytes were reduced, and there was a decrease in radioiron utilization of erythropoiesis, thus indicating insufficient iron supply. The pathogenesis of this disorder based on the formation of an autoantibody with specificity for transferrin thus producing a circulating immune complex which bound the majority of serum iron. Immunosuppression achieved a partial remission including a recovery of the patient's general state, a rise in free transferrin, a decrease in serum iron, disappearance of hemosiderin in the liver, and a rise in erythrocyte production.