Transferrin Saturation Values Research Articles

Screening for hemochromatosis in primary care settings.

Interest in including screening for hemochromatosis in the routine medical care of adults has grown in recent years. In March 1997, at a meeting on iron overload at the Centers for Disease Control and Prevention, the directors of four hemochromatosis screening programs described the major challenges that they faced and the lessons that they learned in implementing their programs. Seven issues were consistently described as important challenges: 1) changes in case definitions of hemochromatosis, 2) selection of screening threshold values and identification of false-positive cases, 3) variability and lack of standardization in screening test measurements, 4) physician education, 5) informed consent and concerns about medical and genetic discrimination, 6) patient compliance with screening and therapy, and 7) incidental detection of iron deficiency. The two programs that have been completed report a prevalence of iron overload from hemochromatosis of 4.2 to 4.5 per 1000 persons screened; this is consistent with findings in the recent literature. All programs report that screening is feasible and propose that hemochromatosis be defined by repeated elevated serum transferrin saturation values(with or without DNA test results) rather than by the clinical outcome of excessive iron in tissue. The goal of screening programs is to diagnose iron status disorders, particularly hemochromatosis, before they lead to iron overload and chronic disease states. Further research is needed on the ability of genetic and phenotypic tests to predict the clinical expression of hemochromatosis. The experiences outlined in this report highlight practical issues that need to be addressed when iron status screening for hemochromatosis is implemented. It is hoped that this information will facilitate similar efforts in other health care settings.

Role of cytokines in the response to erythropoietin in hemodialysis patients

Cytokines are regulatory factors of erythropoiesis, especially in pathologic conditions. Even though a relevant role for a deranged cytokine production in the pathogenesis of dialysis anemia has been suggested, no data are available that analyze the role of cytokines in the key therapeutic issue of the needs of erythropoietin. The aim of the present study in hemodialysis patients was, therefore, to examine the relationship between the dose of recombinant human erythropoietin (EPO) and the production of cytokines by peripheral blood mononuclear cells (PBMC). After the exclusion of subjects with major active causes of EPO resistance, data from 34 hemodialysis patients were available for analysis. Cytokine levels were measured in the supernatants of stimulated [with bacterial lipopolysaccharide and interferon gamma (IFN-gamma)] and unstimulated PBMC. Mean yearly values of hematocrit, hemoglobin, transferrin saturation, ferritin, parathormone (PTH) and aluminum levels and EPO doses (U/kg/week) were calculated. For analysis, the 34 patients were divided according to their cutoff requirements for EPO: patients with requirements of EPO > or = 60 U/kg/week (group A1, 26 subjects) versus EPO < 60 U/kg/week (group B1, 8 subjects) and patients with requirements of EPO > or = 100 U/kg/week (group A2, 18 subjects) versus <100 U/kg/week (group B2, 16 subjects). A significant direct correlation between interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-a) production values and EPO doses was found (P = 0.039 and P = 0.02 respectively). On the other hand, there was a significantly negative correlation between interleukin-12 (IL-12) production values and EPO doses (P = 0.029). Patients of groups A1 and A2 had spontaneously higher tumor necrosis factor-alpha (TNF-alpha) and lower IL-12 and IFNgamma production compared to patients from groups B1 and B2. Our data disclose a previously undescribed pattern of cytokine alteration that is relevant to determine increased needs of EPO in hemodialysis patients. The present results have potential applicability in designing strategies to improve EPO resistance.

Effect of an intravenous iron dextran regimen on iron stores, hemoglobin, and erythropoietin requirements in hemodialysis patients.

Iron deficiency is a common cause of delayed or diminished response to erythropoietin (EPO) in hemodialysis patients. Although oral iron is often prescribed to replete iron stores, this approach to iron supplementation may not be adequate with chronic EPO therapy. Intravenous (IV) iron dextran may be an effective alternative approach to replete iron stores and may facilitate more cost-effective use of EPO. The purpose of this study was to evaluate an IV iron dextran regimen that consisted of a loading dose phase followed by monthly maintenance doses of iron dextran. The effect of this regimen on iron stores, hemoglobin, and EPO doses was evaluated. This was an open prospective study in adult hemodialysis patients who were iron deficient as defined by a serum ferritin less than 100 ng/mL or transferrin saturation (TSAT) of less than 20%. Patients were loaded with 1 g iron dextran in five divided doses and then received monthly maintenance doses of 100 mg for the 4-month study period. Values of serum ferritin, TSAT, hemoglobin, and EPO dose were followed for the 4-month study period. Thirty hemodialysis patients receiving EPO were identified as being iron deficient and were enrolled in the study. The mean serum ferritin increased significantly from 49 ng/mL at baseline to 225 ng/mL at the end of the study period (P < 0.0001). Mean TSAT also increased significantly from 27% to 33% (P = 0.002). Values for hemoglobin did not change significantly during the study period; however, there was a significant reduction in EPO dose from a mean baseline dose of 112 U/kg/wk to 88 U/kg/wk at the end of the study period (P = 0.009). Seventeen patients experienced an increase in hemoglobin or a decrease in EPO dose. Economic analysis showed that approximately $580 (Cdn) per patient per year could be saved by use of IV iron dextran. The administration of the IV iron dextran regimen in the iron-deficient hemodialysis population was effective at repleting and maintaining iron stores and reducing EPO use.

The effect of HFE mutations on serum ferritin and transferrin saturation in the Jersey population.

High frequencies of the haemochromatosis-related HFE C282Y mutation have been reported in North European populations, in which a high proportion of patients with the disease are homozygotes. However, the degree of penetrance of this genotype is unknown. We determined the HFE C282Y and H63D genotypes of 411 consenting volunteer blood donors on Jersey, and the serum ferritin and transferrin saturation levels of 204 of these volunteers. The C282Y allele frequency was found to be 8.3% in 822 chromosomes, indicating a homozygote frequency of 1/145. Consistent with this, four C282Y homozygotes were detected in 411 volunteers. As there are only 18 patients presently receiving treatment for haemochromatosis on Jersey, out of a total population of about 85000, there is a large discrepancy between the number of haemochromatosis patients and the number of C282Y homozygotes in this population. In a preliminary study of 204 consenting volunteers we found a correlation between transferrin saturation and HFE H63D/ C282Y genotype (P=0.017) and between serum ferritin and genotype (P = 0.056). We also observed elevated values of transferrin saturation in the two C282Y homozygotes assayed. These results suggest that a large proportion of the many undetected C282Y homozygotes on Jersey and in similar populations could be in the preclinical stages of haemochromatosis, and warrant investigation. However, there may be a wide variation in the expression of the condition, and a more extensive study of the level of disease penetrance encompassing a large number of hitherto undetected C282Y homozygotes is therefore imperative.

Phenotype-genotype correlation in haemochromatosis subjects.

Haemochromatosis is a common autosomal recessive genetic disorder of iron metabolism. A candidate gene was recently identified (HLA-H) and two amino acid substitutions (C282Y and H63D) were characterized. Haemochromatosis probands (n = 478) from Brittany were selected from their iron status markers, primarily serum iron, serum ferritin and transferrin saturation. We investigated the relationships between haemochromatosis phenotype and genotypes at the HLA-H locus and surrounding markers. As already reported, we observed that the C282Y substitution is unambiguously associated with the haemochromatosis phenotype, haemochromatosis patients homozygous for the substitution (Tyr/Tyr) accounting for 81.2% of all haemochromatosis patients. A clear heterogeneity in serum ferritin and transferrin saturation values, and in iron removed by phlebotomy was observed among haemochromatosis patients that is correlated with the presence of two subgroups of individuals homozygous and non-homozygous for the mutant allele C282Y, the latter being characterized by lower phenotypic values. In this subgroup, sequencing did not reveal any other mutation in the HLA-H gene, hence the genotype remained unclear. Thus, an additional non-genetic cause, other mutations or another gene can not be excluded as explanations for the results in these patients.

Iron depletion without anemia and physical performance in young women

Studies in laboratory animals found that iron deficiency without anemia decreased oxidative capacity and increased reliance on carbohydrate as the substrate for energy, thereby causing impaired endurance. The purpose of this cross-sectional study was to investigate the relation between iron deficiency without anemia and physical performance in healthy active women aged 19-36 y. Iron-status assessment included determination of hemoglobin, hematocrit, transferrin saturation, and serum ferritin values. Dietary iron intake was assessed by frequency questionnaires and physical activity level was estimated by frequency questionnaires and 2-wk records. Fifteen women with normal iron status and 15 women with iron depletion (serum ferritin < 12 micrograms/L) were chosen randomly from a group of 69 nonanemic women and given physical-performance tests, including determinations of maximum oxygen consumption (VO2max), ventilatory threshold, and delta-efficiency. There were no significant differences between the two groups in body size, body composition, physical activity level, dietary iron intake, delta-efficiency, or ventilatory threshold. Compared with the iron-depleted group, the iron-sufficient group had significantly higher hemoglobin, transferrin saturation, and serum ferritin values and a significantly greater tendency to use iron supplements. When physical activity level and fat-free mass were controlled for, the iron-depleted group had a significantly lower VO2max. The difference in VO2max was significantly associated with serum ferritin concentration; hemoglobin value was not a significant confounder. Therefore, reduction of VO2max in nonanemic women with iron depletion was likely caused by factors related to reduced body iron storage but was unrelated to decreased oxygen-transport capacity of the blood.

Correction of Iron Deficiency with an Iron-Fortified Fluid Whole Cowʼs Milk in Children

This study assesses the efficacy of an iron-fortified (15 mg Fe, as stabilized ferrous sulfate (SFE-171), per liter) fluid whole cow's milk (IFFWCM) for the treatment of mild iron deficiency in children. Previous studies in healthy adult volunteers showed a mean 10.2 +/- 4.7% iron absorption. Seventeen children (12 to 48 months old) with iron deficiency (serum iron (SI) < 60 micrograms/dl, transferrin saturation (TS) < 15%, serum ferritin (SF) < 15 ng/ml) were included in this study; 11 of them were anemic. As treatment, they received IFFWCM, instead of the customary whole cow's milk, for at least 4 months; medicinal iron was not administered. Hematocrit (Hct), hemoglobin (Hb), SI, TS, and SF were determined monthly. The Hb increased from 10.3 +/- 0.8 to 12.7 +/- 0.6 g/dl in the group with anemia (delta F-B: 2.4 +/- 1.0 g/dl) and from 12.6 +/- 0.7 to 13.5 +/- 0.3 g/dl in the group without anemia (delta F-B: 0.9 +/- 0.5 g/dl); the difference between both groups was significant (p < 0.01); the rate for Hct values showed a similar pattern. In the whole group, the SI increased to 84.8 +/- 37.4 micrograms/dl, with no difference between children with anemia and children without anemia; TS showed a similar pattern (delta F-B: 19.0 +/- 11.0%). The mean SF increased from 12.1 +/- 2.7 ng/ml to 27.9 +/- 25.4 ng/ml. Normal values for Hct, Hb, SI, and TS were reached by 100% of children; the rate for SF was 56.3%. Time required to reach normal Hct in the children with anemia was 59.4 +/- 33.0 days. Acceptance and tolerance were excellent; no treatment had to be discontinued. The group of patients with anemia was compared with an historical group composed of 55 children matched for age, basal Hct, and achieved Hct increase, treated with medicinal FS (4-6 mg/kg/day): time required to reach normal Hct was shorter in the FS-treated group (39.0 +/- 14.5 days) (p = 0.050). The use of IFFWCM alone could be an effective, relatively inexpensive, and well-tolerated treatment of iron deficiency in children.

Nontransferrin-bound Iron in Serum of Patients Receiving Bone Marrow Transplants

Nontransferrin-bound iron (NTBI) and other parameters of iron status were measured in 40 patients undergoing bone marrow transplantation (BMT) prior to conditioning therapy (between day −10 and −7), at the time of BMT (day 0), and 2 weeks later (day +14). Serum iron and transferrin saturation values were normal before conditioning therapy. At day 0 serum iron values were high and median transferrin saturation was 98% (changes in the values of both serum iron and transferrin saturation, p < .0001). Transferrin saturation values were still elevated 2 weeks posttransplant (day +14 vs. baseline values, p = .0001). Starting at low NTBI levels pretransplant (median 0.4 μmol/l, range 0–4.2 μmol/l, controls: ≤ 0.4 μmol/l), all patients revealed high levels on day 0 (median 4.0 μmol/l, range 1.9–6.9 μmol/l, p < .0001) and 2 weeks posttransplant (median 2.7 μmol/l, range 0–6.2 μmol/l, p < .0001). These observations indicate that the plasma iron pool in patients undergoing BMT increases to a level at which the normal ability to sequestrate iron becomes exhausted and considerable amounts of NTBI appear in serum. This “free” form of iron can mediate the production of reactive oxygen species and may cause organ toxicity in the early posttransplantation period. © 1997 Elsevier Science Inc.

Sensitivity and Specificity of Transferrin Saturation and Serum Ferritin as Markers of Iron Status After Intravenous Iron Dextran in Hemodialysis Patients

This study was designed to investigate the effect of intravenous (i.v.) iron dextran (ID) on hematocrit (Hct), transferrin saturation (TS), and serum ferritin (SF) in hemodialysis patients treated with a constant dose of erythropoietin (EPO). The sensitivity, specificity, and predictive values of SF and TS for monitoring ID therapy were also assessed.All hemodialysis patients with baseline SF < 100 ng/mL or TS < 20%, with EPO dose unchanged 6 weeks before and 4 weeks after dosing with ID were included. ID (500 mg–1 g) was given as an infusion over 1 h. Patients receiving packed RBC or with active bleeding were excluded. Hct, TS, and SF were measured 2 weeks before and 4 weeks after ID. Linear correlation coefficients between dose of ID, changes in Hct, TS, and SF were calculated. The sensitivity, specificity, and predictive values of TS and SF were compared. A positive Hct response was defined as a >5% increase from baseline 4 weeks after administration of ID.Thirty-three patients (17 females) received a total of 51 doses of ID. Mean ± SDID dose was 770 ± 278 mg. Hct increased by a mean ± SD of 4.8% ± 9.9% (33.4% ± 3.0% to 34.9% ± 4.1% [p = 0.028]); SF rose by a median of 208.65% (mean ± SD of 126.8 ± 132.1 ng/mL to 325.3 ± 222.0 ng/mL [p < 0.0001]; TS increased by a median of 53.8% (19.4% ± 9.4% to 29.3% ± 11.3% [p < 0.0001]) from baseline values. The correlations between dose of ID and percent changes in SF, TS, and Hct were poor (r2 < 0.02). The sensitivities and specificities were 74% and 36% (TS < 20% alone); 60% and 30% (SF < 100 ng/mL alone); and 33% and 67% (TS < 20% and SF < 100 ng/mL), respectively. The predictive values for positive responses were 48% for TS and 45% for SF when used alone, and 47% when both indices were used together. The predictive value increased to 65% when either SF < 100 ng/mL or TS < 20% were used.At a constant EPO dose, there was a statistically significant increase in Hct 4 weeks after ID administration in patients who were diagnosed with iron deficiency by using TS < 20% or SF < 100 ng/mL. The dose of ID administered was poorly correlated to changes in Hct, TS, and SF. Both TS and SF are nonspecific and insensitive indicators for accurate diagnosis of iron deficiency in hemodialysis patients in EPO.

Clinical and biochemical abnormalities in people heterozygous for hemochromatosis.

Ten percent of whites are heterozygous for the HLA-linked hemochromatosis mutation. We performed a cross-sectional analysis of 1058 genotyped heterozygotes to define the effects of age and sex on the phenotype. The heterozygous genotype was assigned to 505 male and 553 female members of 202 pedigrees, each with an HLA-typed homozygous proband. We measured serum iron, transferrin saturation, and ferritin in all heterozygotes and in 321 genetically normal subjects (unaffected family members or spouses of family members). Liver biopsies were performed in a subgroup of heterozygotes. The mean serum iron concentrations and transferrin-saturation values were higher in heterozygotes than in normal subjects and did not increase with age. Initial transferrin-saturation levels exceeding the threshold associated with the homozygous genotype were found in 4 percent of male and 8 percent of female heterozygotes. The geometric mean serum ferritin concentration was higher in heterozygotes than in normal subjects and increased with age. Higher-than-normal values were found in 20 percent of male and 8 percent of female heterozygotes. The clinical and biochemical expression of hemochromatosis was more marked in heterozygotes with paternally transmitted mutations than in those with maternally transmitted mutations. Liver-biopsy abnormalities were generally associated with alcohol abuse, hepatitis, or porphyria cutanea tarda. The phenotype of persons heterozygous for hemochromatosis differs from that of normal subjects, but complications due to iron overload alone in these heterozygotes are extremely rare.

The evaluation of iron status in hemodialysis patients.

Effective treatment of anemia in hemodialysis patients requires ongoing monitoring of iron status. The purpose of this study was to determine levels of commonly used iron indices predictive of iron deficiency in this population. Forty-seven patients with baseline serum ferritin levels < 600 ng/mL were treated with intravenous iron dextran (INFeD; Schein Pharmaceutical Inc., Florham Park, NJ), 1000 mg over ten hemodialysis treatments. Patients whose hematocrit value increased by 5% or who had a 10% decrease in their erythropoietin dose by 2 months were classified as having iron deficiency (N = 31; 66%). All other subjects were classified as having adequate iron (N = 16; 34%). There was no statistically significant difference in baseline serum ferritin, transferrin saturation, mean cell volume, mean cell hemoglobin content, or red cell distribution width between the two groups. Receiver operator curves demonstrated that none of the iron indices had a high level of utility (both sensitivity and specificity > 80%). Two tests had marginal utility, serum ferritin at a level of < 150 ng/mL, and transferrin saturation < 21%. It was concluded that because of the tests' marginal utility, they should only be interpreted in the context of the patient's underlying erythropoietin, responsiveness. In patients who are responsive to erythropoietin, a transferrin saturation value < 18% or serum ferritin level < 100 ng/mL should be used to indicate inadequate iron. When erythropoietin resistance is present, transferrin saturation of < 27% or serum ferritin < 300 ng/mL should be used to guide iron management.

Parameters of iron deficiency in children with cyanotic congenital heart disease.

A group of 67 children with cyanotic congenital heart disease (CCHD) were studied, and 35 were given iron treatment according to a regimen that gives iron to patients with a hematocrit (Hct) below 60%. The patients were categorized as iron-deficient and iron-sufficient according to their transferrin saturation and ferritin values. The pretreatment hemoglobin (Hb) and Hct values of the groups were similar. The mean Hct was nearly three times as much as the mean Hb in the iron-sufficient group and more than three times as much as the Hb in the iron-deficient group. Excessive erythrocytosis in the iron-deficient group was impressive. Mean corpuscular volume (MCV) values were below 72.7 fl in all of the iron-deficient patients. After treatment the Hb, Hct, transferrin saturation, and ferritin increased significantly in both groups, with the increments greater in the iron-deficient group. Increments in the erythrocyte (RBC) count were significant in the iron-sufficient group but insignificant in the iron-deficient one. Increments of MCV in the iron-deficient group were significant but insignificant in the iron-sufficient group. Our study demonstrated that prediction of Hb, RBC count, and MCV, measurements of which are easy and inexpensive and require little blood, can suffice for the diagnosis of iron deficiency in patients with CCHD without altering systemic perfusion.

Efficacy of iron repletion in anemic rats after the feeding of a purified or natural-ingredient diet with ferrous sulphate or carbonyl iron

We examined, in rats with iron-deficiency induced anemia, the bioavailability of iron from carbonyl iron versus ferrous sulphate that was incorporated into either a purified or natural-ingredient diet. Various assessments of iron bioavailability were used. Hemoglobin (Hb) values and Hb regeneration efficiency (HRE) after 7 days were higher when ferrous sulphate was given instead of carbonyl iron. After 15 days, there was no longer an effect of supplemental iron source, but now the purified diet produced higher Hb values than did the natural-ingredient diet. After 7 days of repletion, the feeding of the purified diet, when compared to the naturalingredient diet, resulted in higher plasma iron and transferrin saturation values. Apparent iron absorption values were higher with the purified diet. It is concluded that carbonyl iron was less effective than ferrous sulphate in the regeneration of Hb in anemic rats, but this was seen only after 7 days of iron repletion. The diet composition had effects irrespective of the source of supplemental iron. The purified diet, when compared with the naturalingredient diet, further improved the hematological parameters of iron status, raised apparent iron absorption and elevated liver iron mass.

Iron overload in African Americans

Iron overload unexplained by dietary or medicinal iron excess, transfusion, or sideroblastic anemia has been described infrequently in Americans of African descent. The purpose of this study was to characterize iron overload attributable to excessive iron absorption in African Americans. In a community hematology and medical oncology practice during the interval 1990 to 1993, we identified and evaluated a series of cases comprised of 6 men and 1 woman, with a mean age of 55 +/- 14 (SD) years (range 33 to 69). Data on clinical features, serum iron parameters, liver and body iron stores, evaluations of anemia, human leukocyte antigen (HLA) typing, and family studies were analyzed. Among our patients, the serum iron parameters were: iron concentration 26 +/- 13 mumol/L, transferrin saturation 59 +/- 21%, and ferritin concentration 1,588 +/- 1,053 micrograms/L. Clinical abnormalities observed included weakness and fatigue, decreased libido and impotence, hepatopathy, arthropathy, diabetes mellitus, hypogonadotrophic hypogonadism, and hyperpigmentation. Hepatic parenchymal cell iron deposits were increased in each of the 6 patients studied, and Kupffer cell iron deposits were prominent in 4. The occurrence of iron overload was verified by liver iron quantification and therapeutic phlebotomy. Four subjects had alpha-thalassemia minor; 2 others had hemoglobin S and C traits. No proband had HLA-A3 positivity. Four probands had other family members with iron overload. In comparison with Caucasians with hemochromatosis, our patients have slightly lower mean values of serum iron concentration and transferrin saturation, more Kupffer cell iron deposits, a higher incidence of thalassemia and hemoglobinopathy, and infrequent positivity for HLA-A3. Iron overload in African Americans appears to be more similar to that in certain sub-Saharan African natives than to hemochromatosis.

Prevalence of Heterozygotes for Hemochromatosis in the White Population of the United States

In previous studies, the prevalence of HLA-linked hemochromatosis, thought to be the most common genetic illness in whites, has been estimated by identifying homozygotes in the population. Because not all homozygotes express the disease phenotypically, the accuracy of these estimates is uncertain. We analyzed the distribution of transferrin saturation values in the second National Health and Nutrition Examination Survey to estimate the prevalence of hemochromatosis heterozygotes in the US population. After removing values for possible homozygotes, two populations were present (P < .01 for each gender). When weighted to reflect the US adult white male population as a whole, a proportion of 850 per 1,000 (95% confidence interval, 0.81 to 0.89) were included in a population with a lower mean saturation of 29.7% (29.1% to 30.3%), whereas 150 per 1,000 (0.11 to 0.19) comprised a population with a higher mean saturation of 47.0% (45.1% to 49.0%). Similar results were found for the female population. The gene frequencies were estimated to be 0.081 from the male population and 0.070 from the female population corresponding to prevalences of homozygotes of 6.6 and 4.8 per 1,000, respectively. Our results confirm that the gene for hemochromatosis is common.

Extremely elevated serum ferritin levels in a university hospital: Associated diseases and clinical significance

To establish the frequency with which serum ferritin levels > or = 1,000 ng/mL occur in a general hospital population, and to determine the clinical significance of this finding. All serum ferritin determinations performed between June 1992 and July 1993 at the University of Cincinnati Medical Center were reviewed and patients with serum ferritin levels > or = 1,000 ng/mL identified. The medical records of these patients were then reviewed. Of 1,826 serum ferritin determinations performed during the study period, 122 (6.7%) were > or = 1,000 ng/mL. Associated clinical syndromes found in the 95 patients with serum ferritin > or = 1,000 ng/mL included liver disease (20.0%), renal disease (17.9%), malignant disease (17.9%), human immunodeficiency virus (HIV) infection (16.8%), non-HIV systemic infections (15.8%), chronic transfusions (10.5%), and sickle cell syndromes (10.5%). No syndrome usually associated with extreme serum ferritin elevations was identified in 8.4% of patients, and 16.8% of the patients fell into more than one category. The highest mean serum ferritin levels occurred in the chronically transfused and sickle cell groups. Concomitant serum transferrin saturation values were determined with 82 (86.3%) of the elevated serum ferritin levels and did not correlate well with them. The highest mean transferrin saturation levels occurred in the liver disease group. Transferrin saturation > or = 50%, suggestive of iron overload, was significantly more frequent in the liver disease group (P = 0.002); and saturation < or = 15%, suggestive of iron-deficient erythropoiesis, was significantly more frequent in the HIV group (P = 0.001). Outside the setting of clinical syndromes associated with iron overload (liver disease, transfusions, sickle cell syndromes), serum ferritin levels > or = 1,000 ng/mL serve as a nonspecific marker for a variety of significant disorders, including infectious and neoplastic diseases. Further study of the regulation of ferritin production may provide insight into the pathogenesis of disorders associated with extreme serum ferritin elevations.

Iron metabolism and fungal infections in patients with haematological malignancies.

To determine whether iron metabolism influences the incidence of systemic fungal infection in patients with haematological malignancies. The study population comprised 74 patients who had undergone myeloablative chemotherapy. Systemic fungal infections were classified as confirmed (histological confirmation or characteristic septate hyphae) or possible (antibiotic resistant fever which resolved following administration of intravenous amphotericin B, together with either typical radiographic lesions or massive oropharyngeal candidiasis). Parameters of iron metabolism included serum iron concentrations, total iron binding capacity, serum transferrin, and ferritin concentrations and transferrin saturation values. Patients who developed a fungal infection had substantially increased transferrin saturation values and ferritin concentrations at diagnosis together with low serum transferrin and high serum iron concentrations. This profile was present in patients with a fungal infection regardless of the underlying haematological disorder. Increased transferrin saturation values and high ferritin concentrations may be additional risk factors for the development of systemic fungal infection in patients with haematological malignancies.

Iron status markers during pregnancy No relationship between levels at the beginning of the second trimester, prior to delivery and post partum

To evaluate whether levels of iron status markers (haemoglobin, serum transferrin saturation, serum ferritin) in pregnant women, measured in the beginning of the second trimester, could be used to predict levels later in pregnancy, pre partum and post partum. Randomized, double-blind, placebo-controlled parallel study. The Birth Clinic at the Department of Obstetrics, Herning Hospital, Herning, Denmark. One hundred and twenty healthy pregnant women between 14 and 18 weeks of gestation. Sixty-three women were allocated to treatment with tablets containing 66 mg ferrous iron (as fumarate) daily, and 57 women to treatment with placebo. Haemoglobin, serum transferrin saturation, and serum ferritin were measured every 4th week during gestation, prior to delivery, and 1 and 8 weeks post partum. Correlation matrices during pregnancy and post partum were calculated for each iron status marker separately in iron-treated and placebo-treated women. Haemoglobin, transferrin saturation and serum ferritin values at inclusion displayed steadily declining correlation coefficients with values obtained later in pregnancy. There were no clinically relevant correlations to values obtained 8 weeks or less prior to delivery, and no correlations to values post partum. Serum ferritin values at inclusion could not be used to predict values later in pregnancy or post partum. Haemoglobin, transferrin saturation and serum ferritin values measured in the beginning of the second trimester appear to be unsuitable as guidelines for an individual iron prophylaxis in pregnant women.

Sex Differences in Iron Stores of Adolescents

We evaluated iron status and its determinants in healthy adolescents. Fasting morning blood samples from a school-based cross-sectional study were analyzed for serum ferritin (SF), serum iron, total iron-binding capacity, and circulating transferrin receptors. Physical development, chronic disease, medication, dietary intake, and physical activity were assessed using clinical examination, questionnaires, and 7-day records. The risk of having low serum ferritin values was estimated using bivariate and multivariate regression. Subjects were 867 healthy Swedish adolescents, 14- and 17-year-olds (472 boys and 395 girls). SF values increased with pubertal stage in boys but not in girls. Five percent of the boys and 15% of the girls had SF values < 12 micrograms/L. Of the 17-year-old boys, 7% compared to 1% of the 17-year-old girls had SF values > 100 micrograms/L. Forty-one percent of cases with SF values > 12 micrograms/L had serum iron values < 15 microM, and 22% had transferrin saturation values < 16%. Mean total iron intakes of the boys were high [1.6 times recommended daily allowance (RDA)] and mean intakes of the girls were adequate (0.9 times RDA). Low heme iron intakes increased the risk of low iron stores (< 12 micrograms/L) in girls but not in boys. Total iron intake or other dietary factors, physical development, or level of physical activity did not influence the risk of low SF. The findings of this study suggest that the differences in iron status between boys and girls in adolescence results primarily from biological differences other than menstrual bleeding or insufficient iron intake. Furthermore, the results question the role of SF as an indicator of iron deficiency in adolescence, in particular if age and sex are not taken into consideration. We suggest that different reference values for SF, including the cut-off limit for low SF, adjusted for age and sex, should be considered. The high iron intakes and corresponding high SF values found in the older boys are noticeable in light of the possible negative health consequences of iron overload.

Sex Differences in Iron Stores of Adolescents

SummaryWe evaluated iron status and its determinants in healthy adolescents. Fasting morning blood samples from a school‐based cross‐sectional study were analyzed for serum ferritin (SF), serum iron, total iron‐binding capacity, and circulating transferrin receptors. Physical development, chronic disease, medication, dietary intake, and physical activity were assessed using clinical examination, questionnaires, and 7‐day records. The risk of having low serum ferritin values was estimated using bivariate and multivariate regression. Subjects were 867 healthy Swedish adolescents, 14− and 17‐year‐olds (472 boys and 395 girls). SF values increased with pubertal stage in boys but not in girls. Five percent of the boys and 15% of the girls had SF values &lt;12 μg/L. Of the 17‐year‐old boys, 7% compared to 1% of the 17‐year‐old girls had SF values &gt; 100 μg/L. Forty‐one percent of cases with SF values &gt;12 μg/L had serum iron values &lt; 15 μM, and 22% had transferrin saturation values &lt;16%. Mean total iron intakes of the boys were high [1.6 times recommended daily allowance (RDA)] and mean intakes of the girls were adequate (0.9 times RDA). Low heme iron intakes increased the risk of low iron stores (&lt;12 μg/L) in girls but not in boys. Total iron intake or other dietary factors, physical development, or level of physical activity did not influence the risk of low SF. The findings of this study suggest that the differences in iron status between boys and girls in adolescence results primarily from biological differences other than menstrual bleeding or insufficient iron intake. Furthermore, the results question the role of SF as an indicator of iron deficiency in adolescence, in particular if age and sex are not taken into consideration. We suggest that different reference values for SF, including the cut‐off limit for low SF, adjusted for age and sex, should be considered. The high iron intakes and corresponding high SF values found in the older boys are noticeable in light of the possible negative health consequences of iron overload.