Percentage Of Iron Saturation Research Articles

Iron overload in transfusion-dependent β-thalassemia patients: defining parameters of comorbidities

Background Iron overload represents a consistent and almost inevitable complication in patients with transfusion-dependent β-thalassemia. The frequently needed erythrocyte transfusions are known to be the leading source of body iron. Increased iron deposition in tissues was strongly suggested to underlie poor growth and development in transfusion-dependent β-thalassemia. This study aimed to investigate the pattern of increase in iron-overload parameters in relation to the therapeutic measures used and explore its effect on the physical growth of patients with transfusion-dependent β-thalassemia. Patients and methods The study included 60 transfusion-dependent β-thalassemia patients (median age 12.5 years, interquartile range 8-17 years) and 20 age-matched and sex-matched controls; each group was further subcategorized into less than 12-year-old and more than 12-year-old subgroups. The studied clinical parameters comprised weight and height, which were used to calculate the body mass index (BMI). Laboratory assays included complete blood counts for the assessment of pretransfusion hemoglobin, serum iron, total iron-binding capacity, ferritin, and growth differentiation factor 15 (GDF15), and the calculation of the transferrin iron saturation percentage (TISP). Results Less than one-third (30%) of the patients had a low BMI; no patient was overweight or obese. The median pretransfusion hemoglobin was 7.1 g/dl (interquartile range 6.8-7.2 g/dl). Fifty-two (86.7%) patients were inadequately chelated, showing serum ferritin levels more than 1000 ng/ml. In patients older than 12 years of age, the BMI was significantly lower in comparison with controls of the same age subgroup as well as patients less than 12 years old. Patients with a low BMI had significantly higher median values of TISP, ferritin, and GDF15 than those with a normal BMI. GDF15 values of the more than 12-year-old patients showed significant positive correlations with TISP and ferritin levels. Setting optimal cutoffs at 63% for TISP and 1210 ng/ml for serum ferritin (area under the curve 0.965 and 0.957, respectively) had indicated low BMI with higher certainties compared with GDF15 at a level of 10 000 pg/ml (area under the curve 0.783) in the more than 12-year-old patients.Conclusion Avoiding iron overload should be warranted for transfusion-dependent β-thalassemia patients to have normal BMI. Although a high GDF15 level is helpful in pointing toward the development of a low BMI, it added no value to TISP or ferritin as indictors of patients' growth retardation.

Reduction of Serum Hepcidin by Hemodialysis in Pediatric and Adult Patients

Hepcidin, the principal regulator of iron homeostasis, may play a critical role in the response of patients with anemia to iron and erythropoiesis-stimulating agent therapy; however, the contribution of hepcidin to iron maldistribution and anemia in hemodialysis (HD) patients and the ability of HD to lower serum hepcidin levels have not been fully characterized. We measured serum hepcidin using a competitive ELISA in 30 pediatric and 33 adult HD patients. In addition, we determined serum hepcidin kinetics and calculated hepcidin clearance by measuring serum hepcidin before, during, and after HD in eight pediatric and six adult patients. Hepcidin was significantly increased in pediatric (median 240.5 ng/ml) and adult HD patients (690.2 ng/ml) when compared with their respective control subjects (pediatric 25.3 ng/ml, adult 72.9 ng/ml). Multivariate regression analysis showed that serum hepcidin was independently predicted by ferritin and high-sensitivity C-reactive protein in the pediatric group and ferritin, percentage of iron saturation, and high-sensitivity C-reactive protein in the adult group. Hepcidin levels decreased after dialysis from 532 +/- 297 to 292 +/- 171 ng/ml. Hepcidin clearance by HD was 141 +/- 40 and 128 +/- 44 ml/min in pediatric and adult patients, respectively (NS). These findings suggest that hepcidin may mediate the negative effects of inflammation on both disordered iron metabolism and erythropoiesis in HD patients and that intensification of HD could be used therapeutically to reduce hepcidin concentrations and thereby improve erythropoiesis-stimulating agent responsiveness.

New Formula for the Differentiation Between Iron Deficiency Anemia and Thalassemic Carrier in Thalassemic Prevalence Areas: A Study in Healthy School-Age Children.

Abstract 1410Poster Board I-432 INTRODUCTION:In Thailand, the prevalences of iron deficiency anemia (IDA) and thalassemia carrier are high in the range between 20-50%. Screening of both disorders may show the similar results of low hemoglobin (Hb) and mean corpuscular volume (MCV). Therefore, additional laboratory investigations such as ferritin level, percentage of iron saturation, Hb analysis and DNA study may be required for the definite diagnosis, resulting in an increased cost. Previous studies have identified several formulas to differentiate between IDA and thalassemia carrier by using red blood cell (RBC) parameters. However, individual formula may not applicable for particular population. This study aims to establish a formula to differentiae between IDA and thalassemia carrier in school-age children in central Thailand where the prevalences of β and α thalassemia carriers are high. METHODS:After informed consent, blood was collected and tested for complete blood count (CBC), ferritin level, iron level, total iron binding capacity level, Hb analysis, and DNA study for α- thalassemia-1 (or Southeast-Asian deletion). IDA was diagnosed according to the WHO criteria. Iron deficient erythropoiesis (IDE) was defined as normal hemoglobin (Hb) level and low percentage of iron saturation or ferritin levels. Subjects diagnosed of IDA and thalassemia carrier were selected for further analysis. RESULTS:Three hundred and forty-five healthy children, aged (mean±SD) 11.3±1.7 years, were enrolled in the study. The prevalences of IDA, IDE, thalassemia trait (β, a-thalassemia-1, Hb Constant Spring and HbE trait), thalassemia disease (Hb H, β/E and Hb EE), and normal subjects were 11.6%, 38.3%, 26.1%, 2.3% and 28.7%, respectively. The red blood cell (RBC) parameters of normal, IDA, IDE, HbE trait, β trait and α trait groups were shown in the table below. The median (range) values of serum ferritin level in IDA {37.3 (92.6-162.4)}, IDE {34.3 (3-268.2)} groups were significantly different when compared to normal subjects {46.9 (13.4-232.9)}, p<0.001. However, serum ferritin level alone was not enough for the diagnosis of IDA (area under ROC curve of 0.4). Various reported formulas were used to calculate the area under ROC curve, England and Fraser, 0.78; Mentzler, 0.6; Ehsani, 0.57; Shine-Lai, 0.51; RDW/RBC, 0.88; Srivastava, 0.63; RDWI, 0.79; Green and King, 0.82 and RDW, 0.69. The RDW/RBC had the highest area under ROC curve (0.88). Further analysis of the result to differentiae IDA and thalassemia carrier showed that the RDW/RBC value of ≥3 had the sensitivity and specificity of 82.4% and 88.1%, respectively, in our studied subjects. CONCLUSION:Other than the history of iron intake and thalassemia disease in the family, RDW/RBC≥3 may be an additional test to differentiate between IDA and thalassemia carrier in Thai population. In the future, the validity of this formula in a larger scale of population is recommended.GroupHb (g/dL)Hct (%)MCHC (g/dL)MCH (pg)MCV (fL)RDW (%)Platelet x 109Rbc (x1012/L)Normal N=9913.2±0.939.8±2.533.1±0.628.2±3.985.3±3.613.7±1.1312.6±79.94.7±0.3IDA N=4011.2±0.735.0±1.831.6±2.324.0±6.671.6±8.116.1±2.5395.8±88.34.9±0.5IDE N=9913.1±0.739.7±2.033.0±0.627.3±1.982.6±4.814.2±1.2328.8±66.14.8±0.4HbE trait N=3012.8±0.839.0±2.332.8±0.625.3±1.477.0±4.014.3±0.9325.4±57.45.0±0.3β trait N=1012.0±1.137.4±2.529.3±9.123.9±3.973.7±9.716.1±3.4327.8±58.65.1±0.5α trait N=1011.9±0.537.5±1.731.9±0.821.1±1.566.3±4.816.1±1.2334.3±67.95.7±0.5CS trait N=312.7±0.739.5±2.232.0±0.325.1±1.178.4±2.813.9±0.5332±229.95.0±0.1IDE + trait N=3312.8±0.639.4±2.032.6±0.525.1±1.877.1±4.814.5±1.1343±80.35.1±0.4 Disclosures:No relevant conflicts of interest to declare.

Effects of Transferrin (TF) Polymorphism on the Levels of Some Blood Serum Indices in Clinically Healthy Piglets and Piglets with Diarrhoea Caused by &amp;lt;i&amp;gt;Escherichia coli&amp;lt;/i&amp;gt;

Abstract. The effect of transferrin (TF) polymorphism and the levels of some blood serum indices, functionally linked to this protein, were studied. The following determinations were made in the blood serum of 311 hybrid suckling piglets - TF polymorphism, TIBC (total iron binding capacity), TF iron saturation percentage and levels of iron ceruloplasmin (CP) and copper. Clinically healthy piglets and piglets with diarrhoea caused by E. coli were divided into younger (aged 10 to 14 days) and older (aged 15 to 28 days). The piglets showed two genotypes, TF AB and TF BB. The TF BB genotype dominated among clinically healthy piglets, and the TF AB genotype in those suffering from diarrhoea. TF polymorphism differentiated the levels of CP and copper in clinically healthy piglets, and modified iron concentration and TF iron saturation percentage in piglets with diarrhoea. Regardless of health status, age had an almost identical effect on the levels of blood serum indices in piglets of both genotypes. The differences in the levels of CP, iron, and TF iron saturation percentage in healthy piglets and piglets with diarrhoea were modified by the presence of the TFA allele, but in older piglets only.

Total iron-binding capacity calculated from serum transferrin concentration or serum iron concentration and unsaturated iron-binding capacity.

Total iron-binding capacity (TIBC) indicates the maximum amount of iron needed to saturate plasma or serum transferrin (TRF), which is the primary iron-transport protein (1). Theoretically, 1 mol of TRF [average molecular mass, 79 570 Da (2)] can bind 2 mol of iron (55.8 Da) at two high-affinity binding sites for ferric iron (3). Therefore, TIBC correlates well with TRF concentration, and the theoretical ratio of TIBC (in μmol/L) to TRF (in g/L) is 25.1: TIBC (μmol/L) = 25.1 × TRF (g/L) (4)(5). Measurements of TIBC, serum iron, and the percentage of iron saturation of TRF are useful for the clinical diagnosis of iron-deficiency anemia and chronic inflammatory disorders (6)(7) and as screening tests for other clinical conditions (8). TIBC is routinely determined (9)(10)(11)(12) by saturation of TRF with an excess predetermined amount of iron, removal of the unbound iron, and measurement of the iron that is dissociated from TRF. For removal of the unbound iron, magnesium carbonate (9), ion-exchange resin (10), alumina columns (11), or magnetic particles(12) are used. Most direct TIBC measurement methods require manual procedures that involve centrifugation or pretreatment of serum samples. As an alternative to direct measurement methods, TIBC values are also calculated from the sum of serum iron and unsaturated iron-binding capacity (UIBC), both of which are determined by colorimetric methods (calculation method). We developed a direct and fully automated TIBC (DTIBC) assay for use with an automated multipurpose analyzer (13)(14). A fully automated TIBC measurement method is also commercially available (15). In our previous study (14), TIBC values obtained by DTIBC assay correlated strongly with serum TRF concentrations ( r = 0.984; n = 59), and the slope of the regression line was consistent with the theoretical TIBC/TRF ratio. We …

Intravenous iron for the treatment of predialysis anemia

This article, based on our own studies and those of others, presents evidence to show that the anemia of chronic renal failure in the predialysis period is, to a significant extent, caused by iron deficiency and can be improved in most cases by the administration of intravenous (i.v.) but not oral iron. We estimate that in approximately 30% of all predialysis patients with anemia, a target hematocrit (Hct) of 35% can be reached and maintained by giving i.v. iron alone without exceeding currently acceptable limits of serum ferritin (500 microg/liter) or the percentage of iron saturation (40%). If, in addition, subcutaneous erythropoietin (EPO-usually in only low doses-is added, the combination has an additive effect on the Hct response, and almost all anemic predialysis patients can reach and maintain the target Hct of 35% over a one-year period. Therefore, the advantage of maintaining adequate iron stores with i.v. iron is that if EPO is needed, lower doses will be required to achieve the target Hct than if EPO were used alone. This not only avoids the high cost of EPO therapy but also its associated side-effects, especially hypertension. Using Venofer, a ferric hydroxide sucrose complex, as our i.v. iron supplement, we have seen no anaphylactic reactions in over 20,000 infusions over a four-year period in 360 hemodialysis, 123 predialysis, and 58 peritoneal dialysis patients.

Investigations on Red Cell Size Distribution Histograms in Subjects Treated by Maintenance Haemodialysis

In forty-nine subjects on maintenance haemodialysis quantitative information with respect to changes in the erythron was derived from the red blood cell size distribution histogram. Increased values for the fraction of microcytes were observed in seventeen subjects, whereas in three subjects increased fractions of macrocytes were established. Both fractions were found to be increased simultaneously in only one subject. In the case of normal mean corpuscular volume (MCV) values, the fractions of microcytes were shown to be increased in four male and three female subjects. In contrast, MCV values were increased in four male subjects while the fractions of macrocytes did not exceed the reference range. Several causes which may give rise to abnormalities in red blood cell size distribution histograms in subjects treated by haemodialysis are discussed. From the interpretation of results for serum ferritin concentration, serum iron concentration, total iron binding capacity, and iron saturation percentage it is difficult to establish unequivocally whether the iron supply to the patient is appropriate.

Effect of pH and Iron Concentration on Growth of Candida albicans in Human Serum

The in-vitro growth of Candida albicans in serum is markedly inhibited compared with its growth in Sabouraud's broth. The effect of pH and concentration of iron on the ability of C. albicans to grow on these two media was studied. The growth of C. albicans in human sera is inversely proportional to the pH and directly related to the percentage of iron saturation in the serum. A possible mechanism for the observed linear growth rate of Candida in serum with reduction in pH is a concomitant change in the ability of the transferrin molecule to bind iron. The growth-promoting capacity of human serum can be made commensurate with that of Sabouraud's broth by lowering the pH to 6.3 or by adding iron in excess of the total capacity to bind iron. Thus, it is imperative to evaluate the pH and percentage of iron saturation when studying growth of Candida in serum.

Carbohydrate Metabolism and Production of Diffusible Active Substances by Staphylococcus aureus Grown in Serum at Iron Levels in Excess of Siderophilin Iron-saturation and Below

SUMMARY: Results of studies are reported on the carbohydrate metabolic capabilities of cells of Staphylococcus aureus grown in human serum at varied percentage iron-saturations of its contained siderophilin; on the production by such cells of coagulase, hyaluronidase, staphylokinase, and haemolysins; and on the effectiveness of some antibiotics as growth inhibitors under similar in vitro growth conditions. Cocci grown in serum at a normal serum iron level and percentage of iron-saturation show a significant reduction in their endogenous respiration, in their capacity to attack lactate, a complete loss of ability to oxidize formate, and a several-fold increase in anaerobic glycolytic capacity as compared to those cocci grown in serum containing unchelated free ionic iron. These metabolic changes, in conjunction with an observed increased rate of acid production and rate of glucose utilization by the growing culture of ‘low-iron’ cells versus the ‘high-iron’ cells, indicate an increased dependence upon glycolytic rather than oxidative energy production processes by the iron-restricted cells. The strain of S. aureus employed in these studies, although characterized by conventional methods as a producer of coagulase, hyaluronidase, haemolysins, and staphylokinase, did not elaborate any of these pathogenesis-linked factors at detectable levels when grown in normal serum. Coagulase, alone, was found at ‘high-iron’ levels. The amount of dimethoxyphenyl penicillin required to inhibit growth of our S. aureus strain grown in serum increased with increasing percentage of iron saturation of the siderophilin while the effectiveness of a given inhibitory concentration of kanamycin and chloramphenicol was indifferent to any variation in the iron-saturation value.

The Relationship of Transferrin and Iron to Serum Inhibition of Candida Albicans

An intriguing property of human transferrin, a normally occurring beta globulin, is its ability to inhibit the growth of various organisms pathogenic to man (1, 2). This non-specific effect is most likely related to its affinity for iron and the ease with which, by alteration of physiologic conditions, iron binding can be reversed. Whereas the degree of bacteriostasis of Staphylococcus aureus grown in human serum can be inversely correlated with the percentage of iron saturation, other organisms (e.g. Staphylococcus albus) show no growth unless iron is provided in excess of the amount required to saturate transferrin. Serum from agammaglobulinemic patients has both a higher level of heat stable bacteriostatic activity against Bacillus subtilis and an increased unsaturated iron binding capacity (UIBC) compared to normal serum (3). This finding suggested that the increased levels of unsaturated transferrin may represent a compensatory defense mechanism in the agammaglobulinemic host. The addition of purified human transferrin to tissue culture media has also been shown to cause marked suppression of the cytopathogenic effect of several types of virus (4).

Idiopathic Haemosiderosis

Two brothers, one with hepatic haemosiderosis and the other with hepatic haemochromatosis, died with clinical symptoms of acute abdominal pain and irreversible shock. In view of these deaths, 35 relatives were examined. The iron metabolism was studied by determination of the amount of stainable iron in the liver tissue, the fasting serum iron concentration, the iron saturation percentage of transferrin and the iron excretion in 24‐hours urine following intramuscular administration of 1000 mg desferrioxamine B.A defect in iron metabolism was found in three generations. The findings are most readily compatible with the view that a dominant autosomal gene is responsible for the occurrence of the metabolic defect.