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1.
Evaluation of iron stores in hemodialysis patients on maintenance ferric Carboxymaltose dosing.
Diebold, M, Kistler, AD
BMC nephrology. 2019;(1):76
Abstract
BACKGROUND Iron is administered intravenously (IV) to many dialysis patients at regular intervals and iron stores are evaluated through periodic measurements of ferritin and transferrin saturation (TSAT). In patients without kidney diseases, large single doses of IV iron lead to a transient rise in serum ferritin that does not reflect iron stores. It is not known whether and to what extent smaller IV iron doses used to maintain adequate stores in hemodialysis patients lead to transient spurious elevations of ferritin and TSAT. METHODS Ferritin and TSAT were serially determined over four weeks after the administration of ferric carboxymaltose (FCM) in hemodialysis patients on a stable maintenance FCM dosing regimen of 100 mg or 200 mg every four weeks. RESULTS Ferritin values increased by 113 ± 72.2 μg/l (P < 0.001) from baseline to the peak value and remained significantly elevated until two weeks after the administration of 100 mg FCM (n = 19). After the administration of 200 mg FCM (n = 12), ferritin values increased by 188.5 ± 67.56 μg/l (P < 0.001) and remained significantly elevated by the end of week three. TSAT values increased by 12.0 ± 9.7% (P < 0.001) and 23.1 ± 20.4% (P = 0.002) in patients receiving 100 or 200 mg FCM, respectively, and returned to baseline within four days. CONCLUSIONS IV administration of FCM at doses of 100 or 200 mg in hemodialysis patients leads to dose-dependent transient ferritin elevations of extended duration. Temporal coordination of blood sampling for iron status evaluation with the maintenance IV iron dosing schedule is advisable. TRIAL REGISTRATION ISRCTN12825165 (retrospectively registered 01/02/2019).
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2.
Iron deficiency among blood donors: experience from the Danish Blood Donor Study and from the Copenhagen ferritin monitoring scheme.
Rigas, AS, Pedersen, OB, Magnussen, K, Erikstrup, C, Ullum, H
Transfusion medicine (Oxford, England). 2019;:23-27
Abstract
Blood components collected from blood donors are an invaluable part of modern-day medicine. A healthy blood donor population is therefore of paramount importance. The results from the Danish Blood Donor Study (DBDS) indicate that gender, number of previous donations, time since last donation and menopausal status are the strongest predictors of iron deficiency. Only little information on the health effects of iron deficiency in blood donors exits. Possibly, after a standard full blood donation, a temporarily reduced physical performance for women is observed. However, iron deficiency among blood donors is not reflected in a reduced self-perceived mental and physical health. In general, the high proportion of iron-deficient donors can be alleviated either by extending the inter-donation intervals or by guided iron supplementation. The experience from Copenhagen, the Capital Region of Denmark, is that routine ferritin measurements and iron supplementation are feasible and effective ways of reducing the proportion of donors with low haemoglobin levels.
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Iron overload in congenital haemolytic anaemias: role of hepcidin and cytokines and predictive value of ferritin and transferrin saturation.
Barcellini, W, Zaninoni, A, Gregorini, AI, Soverini, G, Duca, L, Fattizzo, B, Giannotta, JA, Pedrotti, P, Vercellati, C, Marcello, AP, et al
British journal of haematology. 2019;(3):523-531
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Abstract
Iron overload (IO) is poorly investigated in the congenital haemolytic anaemias (CHAs), a heterogeneous group of rare inherited diseases encompassing abnormalities of the erythrocyte membrane and metabolism, and defects of the erythropoiesis. In this study we systematically evaluated routine iron parameters and cardiac and hepatic magnetic resonance imaging, together with erythropoietin, hepcidin, non-transferrin bound iron (NTBI), and cytokine serum levels in patients with different CHAs. We found that 40% of patients had a liver iron concentration (LIC) >4 mg Fe/g dry weight. Hepatic IO was associated with ferritin levels (P = 0·0025), transferrin saturation (TfSat, P = 0·002) and NTBI (P = 0·003). Moreover, ferritin >500 μg/l plus TfSat >60% was demonstrated as the best combination able to identify increased LIC, and TfSat alteration as more important in cases with discordant values. Possible confounding factors, such as transfusions, hepatic disease, metabolic syndrome and hereditary haemochromatosis-associated mutations, had negligible effects on IO. Erythropoietin and hepcidin levels were increased in CHAs compared with controls, correlating with LIC and ferritin, respectively. Regarding cytokines, γ-interferon (IFN-γ) was increased, and both interleukin 6 and IFN-γ levels positively correlated with ferritin and hepcidin levels. Overall, these findings suggest the existence of a vicious cycle between chronic haemolysis, inflammatory response and IO in CHAs.
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Serum Ferritin and Glucose Homeostasis in Women With Recent Gestational Diabetes.
Hershenfeld, S, Ye, C, Hanley, AJ, Connelly, PW, Zinman, B, Retnakaran, R
Canadian journal of diabetes. 2019;(8):567-572
Abstract
OBJECTIVES Serum markers of iron storage have been linked to type 2 diabetes; however, the mechanism underlying this association is unclear. In pregnancy, increased serum ferritin has been reported in women with gestational diabetes (GDM), a patient population at high risk of future type 2 diabetes. However, in the years after pregnancy, it is not known if ferritin relates to their diabetes risk or the pathophysiologic determinants thereof (insulin sensitivity and beta-cell function). Therefore, we sought to characterize the relationship between ferritin and glucose homeostasis in the early postpartum years in women with and without recent GDM. METHODS At both 1 and 3 years postpartum, 340 women (105 with recent GDM) underwent serum ferritin measurement and an oral glucose tolerance test that enabled assessment of insulin sensitivity and/or resistance (Matsuda index and Homeostasis Model Assessment [HOMA-IR]), beta-cell function (Insulin Secretion-Sensitivity Index-2 and insulinogenic index/HOMA-IR) and glucose tolerance. RESULTS Serum ferritin did not differ between women who had GDM and their peers at either 1 or 3 years postpartum. Baseline-adjusted change in ferritin between 1 and 3 years correlated with the concomitant change in C-reactive protein (r=0.21, p=0.0002) but was not associated with measures of insulin sensitivity and/or resistance, beta-cell function or glycemia. On adjusted analyses, neither baseline ferritin nor its change from 1 to 3 years was independently associated with any of the following metabolic outcomes at 3-years postpartum: Matsuda index, HOMA-IR, Insulin Secretion-Sensitivity Index-2, insulinogenic index/HOMA-IR, fasting glucose, 2-h glucose or glucose intolerance. CONCLUSIONS Serum ferritin is not associated with glucose homeostasis in the early years after a GDM pregnancy.
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Automated Requests for Thyroid-Stimulating Hormone and Ferretin Tests in Young Primary Care Patients with Anorexia as an Intervention to Improve Detection of Underlying Conditions.
Salinas, M, López-Garrigós, M, Flores, E, Leiva-Salinas, C
Laboratory medicine. 2019;(3):268-272
Abstract
OBJECTIVE To improve clinical laboratory contribution to the treatment of primary care patients with anorexia through automated computerized strategies. METHODS We recorded the number of laboratory requests due to anorexia; the demographic data, laboratory values, and presence of pathological values for the applicable patients. In a prospective study, the laboratory information management system (LIMS) automatically added thyroid-stimulating hormone (TSH) and/or ferritin testing when it was not requested by general practitioners for all primary care patients with anorexia who were younger than 16 years. RESULTS A total of 3562 patients underwent laboratory testing due to anorexia, of whom 47% were younger than 16 years. The tests in which the results most frequently were abnormal were hemoglobin, ferritin, and TSH. TSH results were abnormal in 20% of patients younger than 16 years. Through the intervention, we detected 3 low ferritin values and 7 cases of pathological TSH levels. CONCLUSIONS The LIMS required TSH and ferritin testing in young patients even when not requested, potentially avoiding the adverse effects of iron deficiency and thyroid disorders on neurological development and cognition in those patients.
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The impact of iron chelation therapy on patients with lower/intermediate IPSS MDS and the prognostic role of elevated serum ferritin in patients with MDS and AML: A meta-analysis.
Yang, Y, Tang, Z, An, T, Zhao, L
Medicine. 2019;(40):e17406
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Abstract
Serum ferritin (SF) has been identified as a potential prognostic factor for patients undergoing stem cell transplantation, but the prognostic value of SF in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients and the impact of iron chelation therapy (ICT) on MDS patients are controversial. The present meta-analysis aimed to better elucidate these relationships.Three electronic databases were searched systematically to identify reports on the prognostic role of SF in MDS and AML patients, and those investigating the impact of ICT on prognosis of MDS patients. The hazard ratios (HRs) and its 95% confidence interval (95%CI) were extracted from the identified studies using Cox proportional hazard regression model for overall survival (OS) and progression of MDS to AML.Twenty reports including 1066 AML patients and 4054 MDS patients were included in present study. The overall pooled HRs for OS of AML and MDS patients with elevated SF prior to transplantation was 1.73 (1.40-2.14), subgroup analyses stratified by the cut-off value of SF ≥1400/1000 ng/mL showed that the pooled HRs were 1.45 (0.98-2.15) and 1.65 (1.30-2.10), respectively. The pooled HRs for ICT in MDS patients was 0.30 (0.23-0.40). For ICT, the pooled HRs for the progression of MDS to AML was 0.84 (0.61-1.61).SF has a negative impact on the OS of AML and MDS patients when it is higher than 1000 ng/mL. ICT can improve the OS of MDS patients with iron overload but it is not associated with the progression of MDS to AML.
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Association Between Norepinephrine Levels and Abnormal Iron Status in Patients With Chronic Heart Failure: Is Iron Deficiency More Than a Comorbidity?
Moliner, P, Enjuanes, C, Tajes, M, Cainzos-Achirica, M, Lupón, J, Garay, A, Jimenez-Marrero, S, Yun, S, Farré, N, Cladellas, M, et al
Journal of the American Heart Association. 2019;(4):e010887
Abstract
Background Mechanisms underlying iron homeostasis dysregulation in patients with chronic heart failure remain unsettled. In cardiomyocyte models, norepinephrine may lead to intracellular iron depletion, but the potential association between catecholamines (sympathetic activation markers) and iron metabolism biomarkers in chronic heart failure is unknown. Methods and Results In this cross-sectional analysis, we studied the association between plasma norepinephrine levels and serum iron status biomarkers indicating iron storage (ferritin), iron transport (transferrin saturation), and iron demand (soluble transferrin receptor) in a prospective cohort of 742 chronic heart failure patients (mean age, 72±11 years; 56% male). Impaired iron status was defined as ferritin <100 μg/L or transferrin saturation <20%. Impaired iron status was observed in 69% of patients. In multivariate models, greater norepinephrine levels were associated with impaired iron transport (transferrin saturation <20%, odds ratio=2.28; 95% CI [1.19-4.35]; P=0.013), but not with impaired iron storage (ferritin <100 μg/L, odds ratio=1.25; 95% CI [0.73-2.16]; P=0.415). Norepinephrine was a significant predictor of increased iron demand (soluble transferrin receptor, standardized β-coefficient=0.12; P=0.006) and low transferrin saturation (standardized β-coefficient=-0.12; P=0.003). However, norepinephrine levels were not associated with iron or ferritin levels ( P>0.05). Adjusted norepinephrine marginal means were significantly higher in patients with impaired iron status compared with those with normal iron status (528 pg/mL [505-551] versus 482 pg/mL [448-518], respectively; P=0.038). Conclusions In chronic heart failure patients, increased sympathetic activation estimated with norepinephrine levels is associated with impaired iron status and, particularly, dysregulation of biomarkers suggesting impaired iron transport and increased iron demand. Whether the relationship between norepinephrine and iron metabolism is bidirectional and entails causality need to be elucidated in future research.
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Erythropoietin and ferritin response in native highlanders aged 4-19 years from the Leh-Ladakh region of India.
Yanamandra, U, Senee, H, Yanamadra, S, Das, SK, Bhattachar, SA, Das, R, Kumar, S, Malhotra, P, Varma, S, Varma, N, et al
British journal of haematology. 2019;(2):263-268
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Abstract
The pivotal role of erythropoietin (EPO) in hypoxic adaptation has led to various studies assessing the EPO and ferritin response in native highlanders from Andes and Tibet. We assessed the relationship between EPO, haemoglobin and ferritin in 335 native highlanders (172 boys and 163 girls, aged 4 to 19 years) from Leh-Ladakh, India, who had no history of travel to lowland areas. Complete blood counts, serum EPO and ferritin levels were measured. We stratified study subjects based on age, gender, pubertal status and analysed the EPO and ferritin levels between the stratified groups respectively. The mean EPO level in boys was lower than girls. The mean ferritin level in boys was significantly higher (P = 0·013) than in girls. There was no significant variation in the EPO and ferritin levels amongst the various age groups in our study. Near normal EPO levels since childhood with a negative correlation with haemoglobin is suggestive of a robust adaptive mechanism to high altitude from the early years of life. Low ferritin levels are indicative of decreased iron stores in these native highlanders.
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Changes in the Serum Hepcidin-to-ferritin Ratio with Erythroferrone after Hepatitis C Virus Eradication Using Direct-acting Antiviral Agents.
Inomata, S, Anan, A, Yamauchi, E, Yamauchi, R, Kunimoto, H, Takata, K, Tanaka, T, Yokoyama, K, Morihara, D, Takeyama, Y, et al
Internal medicine (Tokyo, Japan). 2019;(20):2915-2922
Abstract
Objective Hepcidin is a master iron regulator hormone produced by the liver, but precise mechanism underlying its involvement in iron overload in hepatitis C virus (HCV) infection remains unclear. We investigated the serum hepcidin levels against iron overload before and after HCV eradication. Methods We prospectively investigated the iron metabolism characteristics in 24 patients with HCV genotype 1b infection before and after treatment. We also assessed the serum erythroferrone (ERFE) levels to investigate its association with iron metabolism changes. Patients were treated with Ledipasvir 90 mg and Sofosbuvir 400 mg once daily for 12 weeks and observed for 12 more weeks in order to evaluate their sustained virological response. Results Serum hepcidin levels at baseline were in the normal range, although serum ferritin levels were increased. After HCV eradication, both serum ferritin and hepcidin levels were significantly decreased at 24 weeks from baseline (p<0.001, p=0.006, respectively). However, the serum hepcidin-to-ferritin ratios were significantly increased (p<0.001). In addition, the serum ERFE levels were significantly decreased (p<0.001). Increases in the serum hepcidin-to-ferritin ratios were correlated with decreases in the serum ERFE levels (ρ=-0.422, p=0.039). Conclusion Serum hepcidin levels were relatively low against ferritin levels in HCV infection. However, after HCV eradication, the serum hepcidin-to-ferritin ratios were increased. These results indicate the improvement of inadequate hepcidin secretion against iron overload after HCV eradication. Downregulation of ERFE may have affected the improvement of iron metabolism.
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Potential of the multivitamin-mineral-trace element composition LaVita® before, during and after pregnancy.
Doerfler, D, Mosgoeller, W, Endler, TA, Muss, C
Neuro endocrinology letters. 2019;(7):501-514
Abstract
OBJECTIVES Pregnancy is a period in life with a high demand of micronutrients. A prophylactic supplementation of folic acid to reduce the risk of neurological malformations in the newborn is common practice. The array of essential micronutrients during pregnancy includes neurotropic vitamins (Vitamin B6, B12 and folic acid), minerals like iron, and trace elements like zinc. As the serum level of most micronutritients is actively regulated by the organism, a prophylactic broad supplementation with a mild, but effective supplementation typically does not pose any risk for exaggerated serum levels, therefore prophylactic intake may be prefered to blood screening and specific interventions. METHODS To investigate the ingredients' bioavailability of the complex vitamin-mineral-trace element composition LaVita® we recruited healthy volunteers for six months and observed the changes of pregnancy relevant parameters by means of laboratory measures. The study design was prospective, double blind, placebo controlled, and included a "male group control". We determined baseline parameters of folate, vitamin B6 and vitamin B12, iron, zinc, homocysteine and Hb-alpha-1c. After three and six months of daily intake of the study substance the blood tests were repeated and compared to the baseline levels. RESULTS The regular intake resulted in an increase of the supplemented substances' serum levels. The metabolic parameter homocysteine decreased significantly, Hb-alpha-1c was slightly lowered. CONCLUSION The regular intake filled up the respective storage compartments and reservoirs in the tissues, and improved the metabolic status. Female participants tended to benefit more than male. We conclude that the composition is safe, and warrants optimized micronutrient supply during pregnancy or postnatal breastfeeding.