Functional Validation and Clinical Significance Of a Newly Established Non-Transferrin-Bound Iron (NTBI) Assay System Utilizing Conventional Automated Analyzer

Abstract Introduction Iron is an essential metal in the body. However, iron overload is toxic, as excess ‘free’ reactive iron produces damaging free radicals which can lead to cellular and organ damage. Iron homeostasis is therefore tightly regulated. However, when iron balance collapses (as in prolonged transfusion), transferrin (Tf) becomes fully saturated and non-Tf-bound iron (NTBI) appears in serum. NTBI levels are increased in various iron overload states, and decreased after treatment with iron chelators (example deferasirox) in thalassemia and hemochromatosis, and is therefore important in evaluating and monitoring iron toxicity risks. Although several NTBI measurement methods have been reported, they are extremely complicated and low in sensitivity, thus very few laboratories can quantify NTBI. Consequently, NTBI research has not progressed significantly to date. We previously established a novel assay system utilizing automated analyzers (used widely in clinical laboratories for diagnostic testing), which we presented at ASH 2012 poster session. Using this assay, we sought to measure NTBI in iron overloaded animals, healthy volunteers and patients’ sera. Methods Data was analyzed using the HITACHI 7700 auto analyzer. Human serum was obtained from 41 healthy volunteers (16 males, 25 females) and 118 patients (61 males, 57 females) receiving treatment at the Asahikawa Medical University Hospital. Average age of healthy volunteers was 34.4 years and 60.6 years in patients. The primary diagnosis in patients included malignant lymphoma, acute myeloid leukemia, myelodysplastic syndromes, multiple myeloma and others. Patient data, including hemoglobin, biochemical markers including C-reactive protein (CRP), serum iron (sFe), unsaturated iron binding capacity (UIBC) and serum ferritin were obtained from the patients’ records or determined for the healthy volunteers. Mice were administered intraperitoneal injections of physiological saline solution or iron-dextran (Fe 1 mg/day or Fe 10 mg/day) for 5 days, after which serum was collected. Rats received intravenous injections of physiological saline or iron sucrose. Serum was collected after 1, 3 and 6 hours iron injection. Informed consent was obtained from all study subjects, and study protocol and experimental procedures were approved by the Ethical and Animal Experiments Committee of Asahikawa Medical University and Hospital. Statistical analysis was done using Mann-Whitney U-test and Student paired t-test. Results and Conclusion Median NTBI in healthy volunteers was 0.45 μM; no statistical difference was found between the sexes. Median NTBI in the patient group was 0.38 mM, a slight decrease to that of the healthy volunteers (statistical significance p=0.0144). In transferin saturation (TSAT) and NTBI measurement in the patients, NTBI increased markedly as TSAT reached over 80%. A slightly positive correlation was found between sFe and NTBI, but no significant correlation was observed between serum ferritin and NTBI. CRP>0.3 mg/dL is a positive indicator of inflammation, so median NTBI was compared with CRP-positive and -negative groups; NTBI decreased significantly in the CRP-positive group (p<0.05). On the other hand, median serum ferritin significantly increased in the CRP-positive group (p<0.05). This data shows NTBI is an unmistakably unique marker of iron metabolism unlike serum ferritin. This characteristic of NTBI may be helpful in overcoming problems with serum ferritin use as a marker of iron metabolism (serum ferritin is affected by inflammation), and provide additional information that directly reflects changes in iron metabolism, even in inflammatory states. Compared to the control group, a statistically significant increase in NTBI was observed in the Fe 10 mg/day mice group. After intravenous iron administration in the rats, NTBI was 0.16±0.04 μM at pre-treatment, and rapidly increased to 2.78±0.62 μM after 1 hour iron injection; this increase decreased over time, indicating that NTBI can be used not only as a marker to evaluate iron overload but also to precisely monitor dynamic changes in iron in serum. Our novel system revealed new findings and it indicates that this system must be useful for studying the physiological and clinical importance of NTBI. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Iron Metabolism in the Human Body and Setting its Hygienic Limits for Drinking Water. Review. Part 2

Hygiene and Sanitation ◽

10.33029/0016-9900-2020-99-5-504-508 ◽

2020 ◽

Vol 99 (5) ◽

pp. 504-508

Author(s):

Natalija A. Egorova ◽

N. V. Kanatnikova

Keyword(s):

Oxidative Stress ◽

Drinking Water ◽

Iron Overload ◽

Iron Metabolism ◽

Subcutaneous Tissue ◽

Allergic Diseases ◽

The Body ◽

Urogenital System ◽

High Iron Content ◽

Labile Iron Pool

Iron is an assential element for the growth, division, differentiation and functioning of any cell in the body. Iron is virtually important for human and danger at the same time, because with excessive accumulation it causes oxidative stress with formation of highly active oxygen radicals and reactive form of nitrogen that can destroy cell membranes, proteins, nucleic acids, reduce cell viability, with, according to modern concepts, can contribute to the development of many diseases (cardiovascular, rheumatic, gastrointestinal, neurodegenerative, oncological, metabolic and others), and also accelerate the aging process. Part 1 of this review discussed the issues of iron metabolism in human, including its regulation at the cellular and systemic levels, the intake, transport, use, accumulation and export of iron in cells, the role of the labile iron pool in the cytoplasm of cells and plasma non-transferrin bound iron. Data are provided on the causes, frequency and significance of iron overload in the formation of free radicals and the development of oxidative stress. Part 2 of the review provides information on diseases associated with iron overload as well as information on ferroptosis - a new type of iron-dependent regulated cell death. Attention is paid to the works of domestic authors, where it was found that prolonged use of drinking water with a high iron content is unfavorable for the population and leads to an increase in the overall incidence, the development of the diseases of the blood, skin and subcutaneous tissue, musculoskeletal system, digestive system, urogenital system, and allergic diseases. Separate publications are cited on the possibility of a negative effect of iron at concentrations in water of 0.3 mg/l and lower. The material of the review emphasizes the preventive significance of caution attitude to regulating iron in the water in the Russian Federation, where 1/3 of the population uses iron-containing water for drinking, and substantiate the feasibility of establishing a hygienic limit for iron in water not higher than 0.3 mg/l.

Download Full-text

Noninvasive assessment of iron overload by magnetic resonance imaging

Pediatric Hematology/Oncology and Immunopathology ◽

10.24287/1726-1708-2020-19-3-158-163 ◽

2020 ◽

Vol 19 (3) ◽

pp. 158-163

Author(s):

E. E. Nazarova ◽

D. A. Kupriyanov ◽

G. A. Novichkova ◽

G. V. Tereshchenko

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Iron Overload ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Ferritin Level ◽

Iron Concentration ◽

The Body ◽

Iron Accumulation ◽

Resonance Imaging

The assessment of iron accumulation in the body is important for the diagnosis of iron overload syndrome or planning and monitoring of the chelation therapy. Excessive iron accumulation in the organs leads to their toxic damage and dysfunction. Until recently iron estimation was performed either directly by liver iron concentration and/or indirectly by measuring of serum ferritin level. However, noninvasive iron assessment by Magnetic resonance imaging (MRI) is more accurate method unlike liver biopsy or serum ferritin level test. In this article, we demonstrate the outlines of non-invasive diagnostics of iron accumulation by MRI and its specifications.

Download Full-text

High Transferrin Saturation Is Associated with Lower Monocytic Ferritin Heavy Chain Expression in Sickle Cell Anemia Patients

Blood ◽

10.1182/blood.v124.21.4058.4058 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4058-4058

Author(s):

Kleber Yotsumoto Fertrin ◽

Carolina Lanaro ◽

Carla Fernanda Franco-Penteado ◽

Dulcinéia Martins Albuquerque ◽

Betania Lucena Hatzlhofer ◽

...

Keyword(s):

Iron Overload ◽

Sickle Cell ◽

Serum Ferritin ◽

Iron Metabolism ◽

Sickle Cell Anemia ◽

Transferrin Saturation ◽

C Reactive Protein ◽

Iron Storage ◽

Reactive Protein ◽

Ferroxidase Activity

Abstract The pathophysiology of sickle cell anemia (SCA) involves hemolysis, vaso-occlusion and a chronic inflammatory state. Iron overload secondary to blood transfusions is a frequent complication in these patients, but cannot be adequately estimated by serum ferritin levels, because ferritin is also an acute phase reactant. Although excess iron elevates both ferritin levels and transferrin saturation (TSAT) in SCA patients, there is notorious discrepancy between these parameters. Ferritin is composed of heavy (FHC) and light chains (FLC), and ferroxidase activity by FHC is an important cytoprotective mechanism against redox-iron, a product of heme breakdown and largely present in overt iron overload. Previous studies have shown that overexpression of FHC in sickle cell mice prevented free hemoglobin-induced vaso-occlusion. Since ferritin is also highly expressed in circulating monocytes, and these cells have been shown to interact with other cellular types in the sickle cell vaso-occlusive process, we aimed to characterize ferritin chains in monocytes and investigate the relationship with biomarkers of iron metabolism, inflammation and hemolysis. Peripheral blood monocytes from sixteen adult sickle cell anemia patients in steady state were isolated using a double Ficoll-Percoll density gradient to separate monocytes from neutrophils and lymphocytes. FHC, FLC, TLR4 (toll-like receptor 4), and SLC40A1(ferroportin) gene expressions were determined by RT-qPCR. Blood samples were also collected to determine serum ferritin, iron, and TSAT, and plasma levels of lactate dehydrogenase, soluble transferrin receptor, erythropoietin, and C reactive protein. We found that the expression of TLR4, a receptor known to be activated by heme, correlated with FLC, but not FHC expression. Higher TLR4 expression was also associated with higher serum iron, but not with ferritin, TSAT, or LDH. Interestingly, we did not find a correlation between C reactive protein levels and ferritin in this group of patients. As expected, the expressions of both ferritin chains were correlated with each other (P=0.027, r=0.55), but we found the strongest correlation between FHC and TSAT (P=0.0008, r=-0.652). Patients with a TSAT over 40% had significantly lower expression of monocytic FTH (P=0.003). This suggests that either excessive iron can lead to FHC downregulation in monocytes, or that a decrease in monocytic ferritin ferroxidase activity in some SCA patients may impair safe iron storage in ferritin and contribute to the development of higher TSAT, independently from ferritin levels. Our data support that human monocyte regulation of ferritin chains in SCA patients mirrors what has been described in hepatic cells in a sickle cell mouse model. Patients with increased TSAT may be relatively deprived of the cytoprotective ferroxidase activity of FHC, and a relationship between FHC deficiency and complications in SCA remains to be investigated. Further studies should also address whether FHC in monocytes influences cell adhesion, thus supporting an important role for iron trafficking in cells involved in sickle cell vaso-occlusion, and corroborating other studies associating organ damage in SCA with iron metabolism dysregulation. Disclosures No relevant conflicts of interest to declare.

Download Full-text

T2*-magnetic resonance relaxometry of the liver in the quantitative assessment of iron overload

Vestnik of Russian military medical Academy ◽

10.17816/brmma12226 ◽

2018 ◽

Vol 20 (2) ◽

pp. 55-58

Author(s):

A M Titova ◽

G E Trufanov ◽

V A Fokin

Keyword(s):

Magnetic Resonance ◽

Iron Overload ◽

Serum Ferritin ◽

Quantitative Assessment ◽

Accurate Estimate ◽

The Body ◽

Ferritin Concentration ◽

Neoplastic Processes ◽

Serum Ferritin Concentration ◽

Reliable Marker

For objective quantitative assessment of iron overload in 60 patients with hemochromatosis of different genesis, T2*-magnetic resonance relaxometry of the liver was performed. The results of the latter were compared with the concentration of serum ferritin, which is by far the most common marker of iron overload. It has been established that T2*-magnetic-resonance relaxometry is a non-invasive, highly effective method of objective quantitative assessment of iron overload in patients of the hematological profile, in comparison with the serum ferritin concentration, which is not specific, since its change can be influenced by inflammatory and neoplastic processes in The organism, often found in patients with oncohematological profile. Thus, according to T2*-magnetic resonance relaxometry of the liver, all patients were divided into two groups: with iron overload and with no overload, the latter among the total number of subjects was 13,3%. The explanation of the increase in serum ferritin concentration in these patients was the presence of identified inflammatory foci in the body. In most patients (86,6%), iron overload was confirmed by T2*-magnetic resonance relaxometry measurements. However, at each degree of overload, there was no clear regularity in the proportional increase in serum ferritin concentration of the intensity of pathological changes revealed by T2*-magnetic resonance relaxometry. Thus, ferritin cannot remain a reliable marker for iron overload. In general, magnetic resonance T2 *-relaxometry provides the most accurate estimate of the degree of iron overload in the liver. T2*-magnetic resonance relaxometry should be included in the protocol of examination of patients with suspicion of the presence of iron overload.

Download Full-text

Estimation of iron overloads using oral exfoliative cytology in beta-thalassemia major patients

CytoJournal ◽

10.4103/1742-6413.178993 ◽

2016 ◽

Vol 13 ◽

pp. 6 ◽

Cited By ~ 1

Author(s):

Swati Leekha ◽

Amit Kumar Nayar ◽

Preeti Bakshi ◽

Aman Sharma ◽

Swati Parhar ◽

...

Keyword(s):

Iron Overload ◽

Prussian Blue ◽

Serum Ferritin ◽

Thalassemia Major ◽

The Body ◽

Transport Cost ◽

Beta Thalassemia ◽

Safe Procedure ◽

Beta Thalassemia Major ◽

Mucosal Cells

Background: Iron overload is a medical condition that occurs when too much of the mineral iron builds up inside the body and produces a toxic reaction. Thalassemia is a genetic disorder of hemoglobin synthesis, which requires regular blood transfusion therapy, and the lack of specific excretory pathways for iron in humans leads to iron overload in the body tissues. It is a major cause of morbidity and mortality in these patients. The estimation of iron levels in exfoliated buccal mucosal cells may provide a simple, noninvasive, and a safe procedure for estimating the iron overload by using the Perls’ Prussian blue stain. Methods: Smears were obtained from buccal mucosa of 40 randomly selected beta-thalassemia major patients and 40 healthy subjects as controls. Smears were stained with Perls’ Prussian blue method. Blood samples were taken for estimation of serum ferritin levels. Images of smears were analyzed using the software image J software version 1.47v and correlated with serum ferritin. Results: Perls’ positivity was observed in 87.5% of thalassemic patients with a positive correlation to serum ferritin levels. Conclusion: The use of exfoliative buccal mucosal cells for the evaluation of iron overloads in the body provides us with a diagnostic medium that is noninvasive, easy to collect, store, and transport, cost effective, and above all reliable.

Download Full-text

From Renal Siderosis Due to Perpetual Hemosiderinuria to Possible Liver Overload Due to Extravascular Hemolysis: Changes in Iron Metabolism in Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients On Eculizumab.

Blood ◽

10.1182/blood.v114.22.4031.4031 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4031-4031 ◽

Cited By ~ 2

Author(s):

Antonio M. Risitano ◽

Elisa Seneca ◽

Ludovica Marando ◽

Massimo Imbriaco ◽

Ernesto Soscia ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Iron Metabolism ◽

Renal Cortex ◽

Transferrin Saturation ◽

Iron Loss ◽

Hepatic Iron ◽

Intravascular Hemolysis ◽

Hepatic Iron Overload ◽

Spin Echo Sequence

Abstract Abstract 4031 Poster Board III-967 Iron metabolism in PNH patients is dominated by perpetual iron loss consequent to the chronic complement-mediated intravascular hemolysis; thus, they are prone to develop iron deficiency rather than iron overload, even in presence of large transfusional requirement. Eculizumab (Ecu) has proven effective for the treatment of intravascular hemolysis in PNH patients, resulting in reduction and even abolishment of transfusion requirement and improvement of signs and symptoms of intravascular hemolysis; however, Hb gain is heterogeneous among patients, in most cases due to residual C3-mediated extravascular hemolysis hampering Hb normalization. The goal of our study was to identify possible modifications in iron compartmentalization associated with Ecu treatment and possible clinical consequences. We evaluated iron metabolism in 5 untreated PNH patients and 23 who were receiving Ecu (of whom 4 have been also studied before treatment), combining biochemical parameters with a semiquantitative T2* MRI technology. MRI was performed using four gradient-echo sequences and one spin-echo sequence; signal intensity (SI) was measured on images obtained with each sequence by means of three regions of interest placed in the renal cortex, liver, spleen and at the level of the para-spinal muscle, resulting in a semiquantitative SI value (Grandon et al., Radiology 1994). Within the total patient cohort (regardless they were or were not on Ecu), there was a significant correlation between liver SI and serum ferritin (P<0.001), while kidney SI correlated with the presence of hemosiderinuria (HS, P<0.001). All untreated PNH patients showed similar MRI findings, with significant renal cortex siderosis and normal SI in liver and spleen. This was consistent with overt intravascular hemolysis, as confirmed by biochemical routine testing, and consequent perpetual hemosiderinuria; as expected, all these patients had abundant HS. In contrast, the 23 PNH patients on Ecu showed a distinct and heterogeneous pattern. All patients showed a normal renal SI, with the exception of 2 cases who have recently started Ecu and 2 experiencing Ecu breakthrough; these 4 patients had normal hepatic and splenic SI. All of them (but none of those with normal renal SI) had persistent HS, while only the latter 2 had increased LDH; we conclude that these 4 patients have had residual intravascular hemolysis, and that HS was more sensitive than LDH to identify recent history of intravascular hemolysis. In contrast, the majority of patients showed increased hepatic SI: we found 6 cases with moderate and 5 cases with severe iron overload; in some patients, high hepatic SI was associated with increased SI in the spleen. The 4 patients evaluated before and during treatment showed pre-treatment renal siderosis which progressively disappeared after months of Ecu therapy; in 2 of them, who had a longer exposition to Ecu, moderate hepatic iron overload was demonstrated. Hepatic SI significantly correlated with serum ferritin (P<0.05), but not with transferrin saturation nor with LDH. Iron overload was predictable as a result of persistent transfusional need only in two patients with partial response to Ecu; however, within the whole cohort, patients with suboptimal hematological response (i.e., those with persistent Hb<11) were more likely to develop severe hepatic iron overload (P=0.02). Thus, we hypothesized that iron overload in these patients may be pathophysiilogically linked to persistent extravascular hemolysis; we found a direct correlation between liver SI and both % of C3+ PNH RBCs (P=0.02) and absolute reticulocyte count (P=0.02), which were considered markers of extravascular hemolysis (Risitano et al, Blood 2009). In conclusion, we show by T2* RMI that untreated PNH patients have significant renal siderosis, which tends to disappear during Ecu treatment as a result of the blockade of intravascular hemolysis. However, such blockade of urinary iron loss may render PNH patients susceptible to liver iron overload resulting from transfusions, as well as from residual extravascular hemolysis. While is still not clear the proportion of patients developing clinically significant iron overload requiring specific treatment, we provide evidence that iron metabolism substantially changes during eculizumab treatment, and C3-mediated extravascular hemolysis may play a major role in this process. Disclosures: Risitano: Alexion Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Download Full-text

Do We Need the Chelation Therapy during Intensive Treatment of Acute Lymphoblastic Leukemia (ALL) in Children?

Blood ◽

10.1182/blood.v126.23.4881.4881 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4881-4881

Author(s):

Michal Romiszewski ◽

Michal Matysiak ◽

Katarzyna Pawelec

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Chelation Therapy ◽

The Body ◽

Intensive Treatment ◽

Intensive Chemotherapy ◽

Hematopoietic Stem ◽

Ferritin Concentration ◽

Serum Ferritin Concentration ◽

The Mean

Abstract Introduction Children with ALL during the intensive chemotherapy receive multiple transfusions of packed red blood cell (pRBC) that may lead to iron overload. With each transfusion of pRBC the body is supplied with an about 200-250 mg of iron, which excessive accumulation in tissues, due to the lack of mechanism for its active excretion, may cause toxic organ damage. Methods The aim of the study was to evaluate the serum ferritin concentration in children with ALL, depending on the amount of transfused pRBCs and to determine the group of patients with a risk of iron overload. The study patients included 54 children with newly diagnosed ALL treated at the Department of Pediatrics, Hematology and Oncology between 2008 and 2011, according to the ALL IC BFM 2002 therapy protocol. Prior to initiation the treatment and during the intensive chemotherapy, serum ferritin concentration and the number of pRBC transfusions (ml/kg) were assessed separately for each of the three ALL risk groups-standard risk (SR), intermediate risk (IR) and high risk (HR). Results After the intensive chemotherapy the mean ± standard deviation (SD) of serum ferritin concentration in group HR (2770 ± 1175 ng/ml) was significantly higher compared to the median in group SR 844.4 ng/ml (452.5; 1316) (p = 0.0007) and the mean ± SD in group IR-1270 ± 673.1 ng/ml (p = 0.0040). Throughout the intensive chemotherapy children in HR group received the largest volume of pRBC transfusions (ml/kg) (156.2 ± 68.31 ml/kg). In IR and SR groups the amounts of transfused pRBCs were comparable, respectively 113.5 ± 39.86 and 113.8 ± 29.56 ml/kg. Significant positive correlation was found between the serum ferritin concentration and the total amount of transfused pRBCs (ml/kg) after intensive chemotherapy (p <0.0001). After intensive treatment the concentration of serum ferritin exceeding 1000 ng/ml, that has traditionally been used as a trigger for chelation therapy, was found in 30 of 54 patients, for a prevalence in the entire cohort of 55,6% including 6 out of 6 patients in HR group (100%), 14 out of 22 patients in IR group (63,6%) and 10 out of 24 patients in SR group (41,7%). The group of patients with post-treatment serum ferritin concentration exceeding 1000 ng/mL, received significantly more pRBC transfusions (ml/kg) (139.8 ± 44.92) than the groups with serum ferritin levels between 500-1000 ng/mL (103.6 ± 18.96) (p <0.001) and <500 ng/mL-83.52 ± 17.66 (p <0.05). Conclusions These observations indicate a need of monitoring the cumulative volumes of pRBC transfusions, especially in children with ALL HR group. There is a need of routine screening for iron overload using serum ferritin in patients during intensive chemotherapy, in order to identify patients with indications for early iron chelation therapy. This is particularly important because some of them will be candidates to a hematopoietic stem cell transplantation, whereas iron overload adversely affects outcome of transplantation. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Iron Overload Status in Patients with Non-Transfusion-Dependent Thalassemia in China

Blood ◽

10.1182/blood.v128.22.1287.1287 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1287-1287

Author(s):

Rong rong Liu ◽

Yu mei Huang ◽

Peng Peng ◽

Xiao yun Wei ◽

Yu Lei ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Genetic Disorder ◽

Chinese Patients ◽

Beta Thalassemia ◽

Iron Level ◽

Liver Iron ◽

Liver Iron Overload ◽

Medical University ◽

Hbh Disease

Abstract Background: Non-transfusion-dependent thalassemia (NTDT) is a genetic disorder most commonly including beta-thalassemia intermedia (Beta-TI), HbE/Beta thalassemia (HbE/Beta thalassemia), and hemoglobin H disease (HbH disease). NTDT patients can be at risk of iron overload due to increased intestinal iron absorption triggered by chronic anemia, ineffective erythropoiesis and, possibly, decreased serum hepcidin. Despite NTDT is popular in southern China, there is little data evaluating iron overload in Chinese patients. This study aimed at investigating the occurrence, prevalence and severity of iron overload in Chinese population with NTDT. Methods: We evaluated the serum ferritin (SF), liver iron concentration (LIC) and cardiac T2* in 158 NTDT patients (83 with HbH disease, 45 with Beta-TI and 30 with HbE/Beta thalassemia) in China. The median age was 22 years old. The main characteristics of these patients along with the main results of the study were summarized in Table 1. Blood samples were obtained for the assessment of hemoglobin (Hb) and serum ferritin (SF) levels. LIC was assessed by using validated R2 magnetic resonance imaging [MRI] (FerriScan®). Cardiac iron level was measured by MRI T2*. Patients were scanned with MRI 1.5 T (Siemens Avanto, Germany). The study was performed at the First Affiliated Hospital of Guangxi Medical University. LIC < 3mg Fe/g dw and cardiac T2* > 20ms was considered normal. Abnormal LIC can be divided into mild: 3-7mg Fe/g dw, moderate: 7-15mg Fe/g dw, severe: >15mg Fe/g dw. All patients or parents/guardians provided their written informed consent to participate in this study. The study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Guangxi Medical University. Results: The median SF level of 158 NTDT patients was 1,037(27.0-19,704) ng/ ml. LIC was detected in 155 patients (98.1%) and the median LIC value was 8.9(0.6-43) mg Fe/g dw. There were 15 patients (60%) (8 with HbH disease, 5 with Beta-TI and 2 with HbE/Beta thalassemia)<10 years old found liver iron overload. The youngest patient with liver iron overload was 5 years old with 5.6mg Fe/g dw in LIC. Cardiac T2*was assessed in 111 patients (70.2%) and the median cardiac T2* was 32.8(7.5-75.1)ms. The 7 patients (4.4%) (4 with HbH disease and 3 with Beta-TI) had cardiac T2*=<20ms. There was a significant correlation between LIC and SF (r=0.809, p<0.001). No correlation between LIC and Hb, cardiac T2* values can be verified. There was a significant correlation between LIC and age (r=0.497, p<0.001)(Fig 1). The levels of LIC in patients > 30-year old group are significantly higher than those in other groups (Fig 2).The patients with Beta-TI and HbE/Beta thalassemia showed a statistically significant lower Hb and higher values of SF and LIC than those of HbH disease patients. Conclusions: Chinese NTDT patients have a high prevalence of iron overload. The iron overload in patients with Beta-TI and HbE/Beta thalassemia are more serious than those in HbH disease patients. The age of patient is a risk factor of iron overload in NTDT patient. Patients > 30 years old have a high burden of iron overload. Our data shows that the first assessment of MRI LIC should be performed as early as 5 years old. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Deferasirox for the Treatment of Transfusional Iron Overload in Sickle Cell Anemia. Preliminary Results

Blood ◽

10.1182/blood.v112.11.2879.2879 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2879-2879

Author(s):

Rodolfo D Cancado ◽

Maria Cristina A Olivato ◽

Paula Bruniera ◽

Carlos Chiattone

Keyword(s):

Serum Creatinine ◽

Iron Overload ◽

Sickle Cell ◽

Serum Ferritin ◽

Sickle Cell Anemia ◽

The Body ◽

Once Daily ◽

Body Iron ◽

Endocrine Organs ◽

The Impact

Abstract The majority of patients with sickle cell anaemia have received repeated blood transfusions by adulthood. Because the body has no physiological mechanism to actively excrete the excess of iron, chelation therapy is important for the management of iron overload and its complications, including iron deposition into the liver, heart and endocrine organs, eventual death. While studies are limited, progressive iron loading and subsequent tissue injury in sickle cell disease appears similar to other transfused populations. Deferasirox (Exjade, ICL670) is a once-daily, oral iron chelator that is approved for the first-line treatment of chronic transfusional iron overload. Its safety, tolerability and efficacy in reducing body iron burden have been demonstrated in patients with β-thalassaemia major and in other chronic transfusion-dependent anaemias. The objectives of this prospective, non-randomised, phase IV trial were to evaluate the iron overload status, before and after one year-treatment with deferasirox, using liver iron concentration (LIC) by MRI of the liver, MRI cardiac (Cardiac T2*), serum ferritin and the impact of deferasirox treatment on these measurements, and to evaluate the safety and tolerability of this drug. A total of 30 patients with sickle cell anemia and iron overload, defined as the use of ≥ 20 units of RBC units and/or two plasma ferritin levels ≥ 1000 mcg/L during the 6 months preceding enrollment, received starting dose of 20mg/kg/day of deferasirox. Efficacy was assessed monthly by measuring change from baseline in serum ferritin levels. Safety was evaluated on a monthly basis according to the incidence and type of adverse events and measurement of laboratory parameters, including serum creatinine and liver enzyme levels. Mean (range) age 26.4 ± 12.3y (9–49), 83% female, 93% afrodescendent, 60% on regular blood transfusion, mean deferasirox exposure 30.1 ± 5.6 weeks (16–39), mean MRI hepatic (LIC, μmol/g) 233.0 ± 98.8 (45 – 350), mean MRI cardiac (Cardiac T2*, ms) 41.20 ± 5.46 (27.52 – 51.19). Median ± SD and mean (range) serum ferritin level (mcg/L) at baseline and 6 months varied from 2315.5 ± 1083.9 to 2062.5 ± 1320.8 (p=0.032) and 2012.0 (1013–6074) to 1654.0 (688–6729), respectively. The proportion of patients with serum ferritin levels < 2000, 2000- <3000 and ≥ 3000 mcg/L from baseline to 6 months by percentage of patients changed from 50% to 60%, 26.7% to 26.7% and 23.3% to 13.3%, respectively. The most common drug-related AEs were mild, transient diarrhea (23.3%), headache (20.0%) and nausea (16.7%). Maculo-papular skin rash and serum creatinine increases upper limit of normal were observed in 2 (6.7%) patients. No patient experienced progressive increases in serum creatinine or renal failure. Our preliminary data, over 6-month-period of treatment, confirms that deferasirox is effective and generally well tolerated in pediatric and adult patients, and appears to have similar efficacy to deferoxamine in reducing body iron burden in transfused patients with sickle cell anemia. The availability of deferasirox as a once-daily, oral alternative would potentially facilitate improved compliance, and thereby reduce morbidity and mortality from iron overload.

Download Full-text

Iron Overload in a Patient with Non-Transfusion-Dependent Hemoglobin H Disease and Borderline Serum Ferritin: Can We Rely on Serum Ferritin for Monitoring in This Group of Patients?

Case Reports in Oncology ◽

10.1159/000507653 ◽

2020 ◽

Vol 13 (2) ◽

pp. 668-673

Author(s):

Mohammad Ali ◽

Mohamed A. Yassin ◽

Maya Aldeeb

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Ferritin Level ◽

The Body ◽

Gastrointestinal Absorption ◽

Specific Method ◽

Increased Risk ◽

Endocrine Organs ◽

Secondary Iron Overload ◽

Hemoglobin H Disease

Secondary iron overload is a common complication in the context of hematological diseases, as iron accumulates due to different mechanisms including chronic transfusion, increased gastrointestinal absorption, chronic hemolysis and underlying genetic defects leading to an increase in gastrointestinal absorption of iron. Since the body does not have a mechanism to excrete excess iron, it gets deposited in the heart, endocrine organs, and the liver with the latest being affected less commonly than in primary iron overload disorders like hemochromatosis. Patients with hemoglobin H disease, which is a type of α-thalassemia, are usually transfusion independent, except in occasions where an external stressful factor leads to a drop in hemoglobin and necessitates blood transfusion. Despite this, secondary iron overload is commonly encountered in these patients due to increased gastrointestinal absorption of iron. To avoid the complications associated with iron overload, these patients are usually monitored with serum ferritin, which is an inexpensive widely available method to monitor iron overload. MRI of the liver (Ferriscan) is a more sensitive and specific method to monitor these patients and avoid the long-lasting and sometimes irreversible effect of secondary iron overload. Here we present an interesting case of a patient with hemoglobin H disease, who was monitored with serum ferritin. She had a serum ferritin level considered as a borderline risk for morbidities secondary to iron overload, and an MRI of her liver (Ferriscan) showed significant iron deposition in the liver associated with increased risk of complications secondary to iron overload.

Download Full-text