Serum Ferritin Versus T2*Mri For Estimation Of Iron Overload In Children Treated For Hematological Malignancies

Abstract Background. Iron overload (IO) is a complication in transfusion dependent beta thalassaemmia (TDT). Pathogenic variants in genes involving iron metabolism may confer increased risk of IO. The objective of this study was to determine the magnitude of the cardiac and hepatic IO and determine whether pathogenic variants in HFE, SLC40A1 and TFR2 genes increase the risk of IO in a cohort of TDT patients in Sri Lanka.Materials and Methods. Fifty-seven (57) patients with TDT were recruited for this study. Serum ferritin was done once in 3 months for one year in all. Those who were ≥ 8 years of age underwent T2* MRI of the liver and heart. Fifty-two (52) patients underwent next generation sequencing (NGS) to identify pathogenic variants in HBB, HFE, SLC40A1 and TFR2 genes.Results. The mean age (SD) of this cohort was 9.5 (±4.6) years. It comprised of 30 (52.6%) boys and 27 (47.4%) girls. The mean serum ferritin was 3405 (±2670.5) ng/dl. Hepatic IO was seen in 38 (95%) patients and cardiac IO was seen in 17 (42.5%) patients. All patients with cardiac IO were asymptomatic and had normal echocardiogrammes. There was no statistically significant correlation between serum ferritin and hepatic or cardiac IO.32 (61.5%), 18 (34.6%), 2 (3.8%) of patients were homozygotes, compound heterozygotes and heterozygotes for pathogenic variants in the HBB gene. 9 (17.3%) and 3 (5.8%) patients were heterozygotes for pathogenic variants of HFE and SLC40A1 genes respectively. There were no pathogenic variants for the TfR2 gene. The heterozygotes of the pathogenic variants of the HFE and SLC40A1 genes were not at increased risk of IO.Conclusions. Cardiac T2* MRI helps to detect cardiac IO prior to the onset of symptoms when the echocardiogramme is normal. It is important to perform hepatic and cardiac MRI T2* to detect IO in patients with TDT.

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Serum Ferritin and Cardiac/Liver Magnetic Resonance Imaging In Evaluating Iron Overload for Patients with Bone Marrow Failure Conditions Undergoing Non-Myeloablative HSCT

Blood ◽

10.1182/blood.v116.21.1331.1331 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1331-1331

Author(s):

Victoria J Tindell ◽

Victoria T Potter ◽

Rachel Kesse-Adu ◽

Laura Reiff-Zall ◽

Aloysius Y Ho ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Bone Marrow Failure ◽

Acute Phase Reactant ◽

Hepatic Iron ◽

Red Cell ◽

Resonance Imaging ◽

Phase Reactant ◽

The Impact ◽

T2 Mri

Abstract Abstract 1331 Several groups have identified iron overload, in terms of raised pre-transplant serum ferritin levels, as an independent adverse prognostic factor for patients undergoing myeloablative HSCT. While serum ferritin has been used as a common marker in clinical studies to evaluate the impact of iron overload following allogeneic transplantation, there are limitations to its use with it being an acute phase reactant, as well as its lack of specificity for predicting end-organ toxicities. Patients undergoing HSCT for bone marrow failure (BMF) syndromes usually have a significant red cell transfusion history, and although the majority of these patients receive non-myeloablative HSCT regimens, it is unclear as to the impact of iron overload in these patients on subsequent transplant outcomes. In order to address these questions, we performed a prospective study evaluating the pre-transplant serum ferritin together with concurrent T2* cardiac magnetic resonance imaging (MRI) and R2 liver MRI in 18 patients with BMF syndromes undergoing allogeneic HSCT. The diagnosis of the patients included MDS (RCMD/hypoplastic MDS) =10, acquired aplastic anaemia =7, fanconi anaemia =1. The median age of the patients at transplantation was 42 years, and all patients received a T-cell depleted non-myeloablative HSCT. All patients were transfusion dependent pre-HSCT, with a median number of red cell transfusions of 45 (range: 8–115). Pre-HSCT ferritin was performed within 2 weeks of HSCT, and the results were correlated with albumin and C-reactive protein to reduce the impact of ferritin as an acute phase reactant. T2* and R2 MRI were similarly performed within 2 weeks of HSCT. The median pre-HSCT ferritin was significantly raised at 2119 ug/l(range: 559–12235). In contrast, the T2* cardiac MRI was normal for all but one patient who had evidence of mild cardiac iron overload. All patients had a corresponding cardiac echocardiogram performed with an ejection fraction within normal limits. For the liver T2* MRI, 7 patients had evidence of none or mild hepatic iron overload, while 11 patients had moderate to severe iron overload. There was no correlation between pre-HSCT transfusion burden and serum ferritin levels. Furthermore, there was no correlation between either the transfusion burden or serum ferritin, and the T2*MRI readings. In terms of HSCT outcome, the median time to neutrophil engraftment was 14 days. 2 patients had primary graft failure and only 1 patient died within 100 days due to an intra-cerebral haemorrhage. No patients had any clinical features of hepatic veno-occlusive disease (VOD), and 5 patients had evidence of grade I-II acute grade versus-host-disease. Data were also collected on the incidence of bacterial, fungal and viral infections post-HSCT for the cohort. There was however no significant association between transfusion burden, serum ferritin or T2* imaging and any of the HSCT outcomes (engraftment/day 100 TRM, GvHD, VOD or infections). In the context of heavily transfused BMF patients receiving allogeneic HSCT, serum ferritin does not correlate with end-organ deposition of iron. Despite the high transfusion burden in our cohort of patients, cardiac deposition of iron appears minimal while hepatic iron deposition is significant in a large proportion of patients. Reassuringly, a raised iron overload by either of the above mentioned parameters had no effect on HSCT outcomes. Our findings highlight the limitations of using serum ferritin as a marker of iron overload pre-HSCT. The role of active pre-HSCT chelation of BMF patients receiving non-myeloablative HSCT regimens remains unclear, and further studies are warranted. Disclosures: No relevant conflicts of interest to declare.

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Correlation between serum ferritin level, cardiac and hepatic T2-star MRI in patients with β-thalassemia major in Al-Diwaniya thalassemia center

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v9ispl1.1392 ◽

2018 ◽

Vol 9 (SPL1) ◽

Author(s):

Alaa Mutter Jabur Al-Shibany ◽

AalanHadi AL-Zamili

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Chelation Therapy ◽

Ferritin Level ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Iron Level ◽

The Mean ◽

T2 Mri

Patients with transfusion dependent thalassemia major is often associated with iron overload. Proper use of iron chelators to treat iron overload requires an accurate measurement of iron levels. Magnetic resonance T2-star (T2* MRI) is the preferred method to measure iron level in the liver andthe heart. The goal of our study was to see if there is an association exists between serum ferritin level and T2* MRI results in patients with beta thalassemia major.This study was done in Al-Diwaniya Thalassemia center,Maternity and children teaching hospital,Iraq. During the period from 1st of January to 31st of October. Fifty eight patients with a diagnosis of beta thalassemia major were enrolled in the study. They were older than five years old,transfusion dependent and on chelation therapy. Hepatic and Myocardial T2*MRI and the mean serum ferritin levels were measured during the study period for all patients.There is a significant correlation was observed between serum ferritin level and cardiac T2*MRI (p=0.018 ). also a significant correlation was observed between serum ferritin and hepatic T2*MRI (p=0.02). Neither cardiac T2* MRI nor hepatic T2* MRI show any correlation with the mean age.our study also showa positive correlation between the patients withcardiac T2* MRI and the development of diabetes mellitus in contrast to hepatic T2* MRI in which there is no any correlation. Hypothyroidism was observedno correlation with either cardiac or hepatic T2* MRI.Our results showed a positiveassociation between hepatic, cardiac T2*MRI and serum ferritin levels.

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Discrepancy between Serum Ferritin and Liver Iron Concentration in a Patient with Hereditary Hemochromatosis – The Value of T2* MRI

Case Reports in Oncology ◽

10.1159/000507756 ◽

2020 ◽

Vol 13 (2) ◽

pp. 712-715

Author(s):

Mustafa A. Al-Tikrity ◽

Mohamed A. Yassin

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Ferritin Level ◽

Hereditary Hemochromatosis ◽

Iron Concentration ◽

Hfe Gene ◽

Liver Iron Concentration ◽

C282y Mutation ◽

Liver Iron ◽

T2 Mri

Primary hemochromatosis is an inherited disorder, and the homeostatic iron regulator (HFE) gene C282Y mutation is a common cause of hemochromatosis in Europe. We are reporting a case of a 56-year-old female known to have hemochromatosis with the HFE gene C282Y mutation with a serum ferritin level of 482 μg/L who underwent heart and liver T2* MRI which showed no evidence of iron overload – neither in the heart nor in the liver. This indicates that there is a discrepancy between serum ferritin and liver iron concentration by MRI and the superiority of T2* MRI in diagnosis and follow-up of iron overload in patients with hereditary hemochromatosis.

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Phlebotomy and Hydroxyurea for Non-Transfusion Dependent Iron Overload in Beta-Thalassemia Intermedia

Blood ◽

10.1182/blood.v124.21.4031.4031 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4031-4031

Author(s):

Oscar Boutros Lahoud ◽

Velta Willis ◽

William B. Solomon

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Chelating Agents ◽

Iron Deposition ◽

Beta Thalassemia ◽

Thalassemia Intermedia ◽

Ineffective Erythropoiesis ◽

Clinically Significant ◽

Iron Chelating Agents ◽

T2 Mri

Abstract Background: Patients with beta-thalassemia intermedia are at increased risk of developing clinically relevant iron overload independent of blood transfusions, which can result in serious sequelae, including liver, myocardial and endocrine dysfunction. This is thought to be modulated by downregulation of hepcidin and upregulation of ferroportin1. Standard of care in these patients has essentially consisted of iron-chelating agents such as deferasirox, presumably based on the hypothesis that phlebotomy would worsen clinical anemia and potentially exacerbate further ineffective erythropoeisis2. We present the cases of two patients with non-transfusion dependent iron overload secondary to beta-thalassemia intermedia, who were treated with serial phlebotomies as well as hydroxyurea. Case #1: Patient A was heterozygous for the Gln39X beta zero thalassemic allele as well as heterozygous for the H63D HFE-1 allele, and presented with a serum ferritin of 1928 ng/ml. T2* MRI of liver and myocardium demonstrated mild iron deposition in the liver and none in the heart. During a period of 18 months Patient A received serial phlebotomies and hydroxyurea 500 mg daily with decrease in serum ferritin to 770 ng/ml with no change in her baseline Hb and an increase in Hb F from 7% to 15%. Repeat T2*MRI of the liver and myocardium demonstrated no clinically significant iron deposition. Patient A continues to be phlebotomized every one to two months. Case #2: Patient B was heterozygous for the Gln39X beta zero allele with no mutant HFE-1 alleles, and presented with a serum ferritin of 1230 ng/ml. T2* MRI of the liver and myocardium demonstrated iron deposition in the liver and none in the heart. Over a period of twelve months patient B received serial phlebotomies and hydroxyurea 500 mg daily with decrease in his serum ferritin to 450 ng/mL, with no change in baseline Hb and no increase in Hb F. Repeat T2* MRI demonstrated no cardiac iron overload and slight improvement in the liver T2* relaxation time. Patient B continues to be phlebotomized every one to two months. Discussion: We presented two cases of non-transfusion dependent iron overload secondary to beta thalassemia intermedia managed with the combination of phlebotomy and low dose hydroxyurea, which resulted in clinically significant decrease in serum ferritin. In both patients the decrease in serum ferritin averaged ~65 ng/ml/month. As a reference, the higher dose regimen of deferasirox 10 mg/kg/d has a reported average decrease in serum ferritin of around 222 ng/mL/year, corresponding to an estimated 18.5 ng/mL/month2. There was no change in either patient’s Hb/Hct or markers of ineffective erythropoiesis such as LDH, indirect bilirubin and reticulocyte count. This could be due to a somewhat protective effect from hydroxyurea, which may decrease unbound alpha-globin chains, thereby permitting phlebotomy while maintaining adequate counts. Conclusion: These two cases suggest that in some non-transfusion dependent patients, the combination of phlebotomy and hydroxyurea may be an appropriate first-line treatment of iron overload due to beta-thalassemia. It appears to potentially offer enhanced efficacy with presumably less toxicity than standard iron-chelating agents in selected patients. Further investigation is needed to determine the specific population that would benefit most from this combination. The optimal treatment modality/combination in those patients has yet to be determined. Additional studies about treatment effect on iron-regulatory pathways are warranted. References: (1) Gardenghi S, et al. Ineffective erythropoiesis in beta-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin. Blood 2007: 109(11):5027-5035. (2) Taher AT, et al. Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia: 1-year results from a prospective, randomized, double-blind, placebo-controlled study. Blood 2012; 120(5): 970-977. Disclosures No relevant conflicts of interest to declare.

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Evaluation of iron overload by cardiac and liver T2* in β-thalassemia: Correlation with serum ferritin, heart function and liver enzymes

Journal of Cardiovascular and Thoracic Research ◽

10.34172/jcvtr.2021.18 ◽

2021 ◽

Vol 13 (1) ◽

pp. 54-60

Author(s):

Hengameh Khadivi Heris ◽

Babak Nejati ◽

Khatereh Rezazadeh ◽

Hossein Sate ◽

Roya Dolatkhah ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Liver Enzymes ◽

Heart Function ◽

Ferritin Level ◽

Diagnostic Methods ◽

Iron Load ◽

The Relationship ◽

T2 Mri

Introduction: In this study, we aimed to assess the relationship of cardiac and hepatic T2* magnetic resonance imaging (MRI) values as a gold standard for detecting iron overload with serum ferritin level, heart function, and liver enzymes as alternative diagnostic methods. Methods: A total 58 patients with beta-thalassemia major who were all transfusion dependent were evaluated for the study. T2* MRI of heart and liver, echocardiography, serum ferritin level, and liver enzymes measurement were performed. The relationship between T2* MRI findings and other assessments were examined. Cardiac and hepatic T2* findings were categorized as normal, mild, moderate, and severe iron overload. Results: 22% and 11% of the patients were suffering from severe iron overload in heart and liver, respectively. The echocardiographic findings were not significantly different among different iron load categories in heart or liver. ALT level was significantly higher in patient with severe iron overload than those with normal iron load in heart (P=0.005). Also, AST level was significantly lower in normal iron load group than mild, moderate, and severe iron load groups in liver (P<0.05). The serum ferritin level was significantly inversely correlated with cardiac T2* values (r = -0.34, P=0.035) and hepatic T2* values (r = -0.52, P=0.001). Conclusion: Cardiac and hepatic T2* MRI indicated significant correlation with serum ferritin level.

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The Role of Cardiovascular T2*MRI and Tissue Doppler Measurement in Assesment of Cardiac Status in β-Thalassemia Major

Blood ◽

10.1182/blood.v124.21.1363.1363 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1363-1363

Author(s):

Adalet Meral Gunes ◽

Melike Sezgin Evim ◽

Özlem Mehtap Bostan ◽

Aysel Kaderli ◽

Birol Baytan

Keyword(s):

Iron Overload ◽

Right Ventricular ◽

Serum Ferritin ◽

Systolic Function ◽

Ferritin Level ◽

Study Group ◽

Left And Right ◽

Cardiac Status ◽

Mri Score ◽

T2 Mri

Abstract Introduction: Early detection of myocardial dysfunction and modification of treatment may prevent from progressing into the end stage heart failure and lethal arrhythmias in beta-thalassemia major (β-TM). T2* magnetic resonance imaging (MRI), a non-invasive technic determining iron accumulation in myocardium has been widespreadly used in these patients. Cardiac T2* MRI is not capable to evaluate cardiac functions but, indicates patients with risk for developing cardiac disease. Therefore, combining T2*MRI with tissue Doppler (TD) echocardiography, another technic defining both functional and structural evaluation of myocardium, could give a better information in evaluating the actual status of myocardium. The aim of this study was to evaluate cardiac status of thalassemics by using both T2*MRI and TD measurement. Methods: The study group includedpatientswith β-TM on regular transfusion and chelation program with preserved systolic function; ejection fraction > 55% and fractional shortening > 30% determined by conventional echocardiography. None of them had other organ dysfunctions adversely effecting cardiac functions. The control group was consisted of age and sex matched healthy persons. Serum ferritin levels were measured in both groups. In addition, TD measurements (S,E,A waves, time intervals; ejection time, total systolic time, isovolumetric accelaration time, isovolumetric contraction time, isovolumetric relaxation time and myocardial performance index) were obtained from three different regions of myocardium; septum, left and right ventricular posterior walls. T2* MRI was only determined in thalassemics. The study group was divided into two different subgroups according to serum ferritin level (low ferritin < 2500 ng/ml and high ferritin > 2500 ng/ml) and T2* MRI score (iron overloaded <20 ms and unloaded >20ms). The results obtained by TD within these subgroups were compared. TD measurements in thalassemics without cardiac iron overload were separately compared with the controls. Results: The study and control groups were consisted of 33 β-TM patients (16 girls/17 boys, mean age 18,7±7,7 years) and 37 healthy individuals (18 girls/19 boys, age 19,9±8,4 years), in respectively. Gender and age were similar (p>0,05). Systolic and diastolic functions by TD were found significantly impaired in thalassemics compared to the controls (p<0,05). S-lateral wave measurement showing early myocardial systolic function was more adversely effected in thalassemics (p<0,001). The patients' mean ferritin level was found 2242,3±2174,2 ng/ml (109-9843). Twelve patients (36,4%; 12/33) had high ferritin level and the rest (63,6%; 21/33) had low. T2*MRI and TD measurements did not differ in both subgroups (p>0.05). The mean T2*MRI score was 18,7±7,7 (7,3-29,8) ms in the study group. Twenty-one patients (63,6%; 21/33) had myocardial iron overload. Serum ferritin levels were similar between iron overloaded and unloaded groups (p>0.05). Both isovolumetric acceleration time of left ventricule and myocardial performance index (MPI-septal) showing systolic and diastolic functions were found significantly impaired in iron overloaded subgroup (p<0,05). There was negative correlation between MPI-septal and T2*MRI measurements in thalassemics (r:-0,343, p=0,050, fig 1). When we compared the velocity measurements (S,E,A waves) of iron unloaded thalassemics with the controls; only S wave velocity obtained from left ventricular wall was found significantly low (p<0,05). The time intervals measured from septum were found similar with the controls (p>0,05) but, the same measurements obtained from left and right ventricular posterior walls were significantly impaired (p<0,05). Figure 1: Correlation between Cardiac T2*MRI score and MPI-septal Figure 1:. Correlation between Cardiac T2*MRI score and MPI-septal Conclusions: This study showed that thalassemics with iron overload had significantly impaired TD measurements and MPI-septal index worsened when the mycardial iron load was increased (fig 1). Patients considered as iron unloaded according to T2*MRI result had left and right ventricular dysfunction determined by TD. Normal cardiac T2*MRI does not always associated with normal cardiac function. Therefore, we conclude that combining T2*MRI with TD measurements in evaluating cardiac status in β-TM, especially in patients with normal T2*MRI score, could lead to a better management of cardiac complications. Disclosures No relevant conflicts of interest to declare.

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Transient Elastography of Liver in Hb E Beta Thalassemia: A Novel Tool to Determine Hepatic Iron Overload?

Blood ◽

10.1182/blood.v126.23.3368.3368 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3368-3368

Author(s):

Debmalya Bhattacharyya ◽

Maitreyee Bhattacharyya ◽

Saswata Chatterjee ◽

Abhijit Chowdhury ◽

Pramit Ghosh

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Ferritin Level ◽

Liver Stiffness ◽

Beta Thalassemia ◽

Hepatic Iron ◽

Hepatic Iron Overload ◽

Number Of Patients ◽

T2 Mri

Abstract Introduction: Transient Elastography (TE) of liver is a well established tool to measure liver stiffness, mainly used for assessment of hepatic fibrosis due to chronic hepatitis. Liver biopsy is the gold standard test for measurement of liver iron concentration (LIC) whereas T2* MRI is the best available non-invasive method for the same in thalassemia. We intended to use hepatic TE as an alternative cheaper tool to assess hepatic iron overload so that it can be applied to larger number of patients. Objective: To assess degree of liver stiffness by TE in patients with HbE beta thalassemia and correlate the findings with LIC calculation by T2* MRI of liver. Materials and Method: 53 patients with HbE beta thalassemia from the thalassemia clinic of Institute of Haematology and Transfusion Medicine, Medical College, Kolkata were enrolled for the study. Patients with known liver disease were excluded. Baseline data like HbE%, mutations, transfusion requirement, growth status, serum ferritin level etc were collected. All of them underwent TE of liver in the School of Digestive and Liver Diseases, IPGMER using the FibroScan Touch 502 machine (Di Marco et al, British Journal of Haematology, Volume 148,3, 476-479, February 2010). 20 randomly selected patients were also assessed by T2*MRI of liver for hepatic iron assessment at the same time. LIC calculation was done from T2* value (J S Hankins et al, Blood, 14 May 2009, Volume 113:20). Data were analyzed by SPSS software-19, IBM. Results: The patients with HbE beta thalassemia had a mean HbE level of 53.66 (±18.45) %. Common beta mutations [mostly IVS-1-5(G-C)] usually found in this part of India, were detected. Mean and median age of the study population was 24.11±13.11 years and 20 years, respectively. Median age of 1st transfusion was 11 years. 35.84% patients were non-transfusion dependent. 39/53 patients had facial deformity and growth retardation. Mean baseline hemoglobin was 7.10±0.76 gm/ dl. Mean serum ferritin level was 3183.66±338.45 ng/ml. TE showed 30.18 % patients had severe liver stiffness (Liver stiffness measurement, LSM >15 kPa) whereas 43.34% had minimum stiffness (LSM≤7 kPa). No significant statistical correlation was found between serum ferritin and LSM. 12/20 patients showed very high calculated LIC (>15 mg/g) and lower T2* value (<1.8 ms) whereas only 10% of them showed mildly elevated calculated LIC. Rest had intermediate LIC. Discussion: There is lack of data regarding hepatic iron overload in HbE beta thalassemia and so also from this part of India. There was a trend that higher the age, higher was the LSM irrespective of the serum ferritin level though not found statistically significant (Figure 1). Serum ferritin level was also not significantly correlated with the calculated LIC in those 20 patients assessed with T2* MRI. 2 patients with mildly elevated LIC had a high ferritin level. Preliminary report indicates that with increase in LSM there was increase in calculated LIC also. Statistical analysis revealed patients with LSM≥7.2 kPa had moderate or severe hepatic iron overload and thus undermine the need for routine T2*MRI. The cut off value signifies that patients with LSM<7.2 kPa might or might not have significantly high liver iron overload, so obviously to be assessed by T2*MRI (Table 1). Therefore use of TE may be an alternative preliminary diagnostic method to gauge hepatic iron overload in HbE beta thalassemia patients. It would be of more value in countries like India where T2* MRI facility is not yet feasible in many centers catering to huge number of HbE-beta thalassemia patients. However, further exploration with larger number of patients is necessary to establish association of LIC and LSM in a more robust way. Conclusion: In resource-poor countries like India, TE may be a relatively cheap tool to be used as a marker of hepatic iron overload in future. Table 1. Finding Cut off: ROC (TE-value and LIC categories), n=20 Positive if Greater Than or Equal Toa Sensitivity 1 - Specificity 2.3 1.00 1.00 3.4 1.00 .50 4.4 .94 .50 5.7 .88 .50 6.2 .83 .50 6.5 .77 .50 7.2 .77 .00 8.2 .72 .00 8.85 .66 .00 9.45 .61 .00 10.2 .55 .00 11.85 .50 .00 13.85 .44 .00 15.75 .38 .00 18.3 .33 .00 22.9 .27 .00 27.9 .22 .00 35.9 .16 .00 44.7 .11 .00 48.0 .05 .00 49.8 .00 .00 Table 2. The smallest cutoff value is the minimum observed test value minus 1, and the largest cutoff value is the maximum observed test value plus 1. LSM more than 7.2 had a sensitivity of 77.2 % and specificity of 100%. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

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T2* MRI Provides No Evidence for Myocardial and Pancreatic Iron Overload in Multitransfused Patients with Sickle/β-Thalassemia.

Blood ◽

10.1182/blood.v112.11.1422.1422 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1422-1422 ◽

Cited By ~ 1

Author(s):

Hussam Ghoti ◽

Orly Goitein ◽

Elie Konen ◽

Ariel Koren ◽

Carina Levin ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Iron Content ◽

Transferrin Saturation ◽

Left Ventricular ◽

Iron Deposition ◽

Liver Iron ◽

Cardiac Iron ◽

Cardiac Iron Overload ◽

T2 Mri

Abstract Introduction: Transfusion-dependent hemolytic anemias particularly thalassemia major (thal.m) and also sickle cell disease (SCD) result in iron deposition in the reticuloendothelial system in major organs, mainly in the liver and also in the heart and endocrine glands. However, liver iron levels in patients with thal.m measured by other techniques were found to have no predictive values for the extent of their cardiac iron deposition. T2* MRI sequences have been previously addressed as a reliable tool for non invasive evaluation of iron load in the liver, heart and pancreas. Patients with T2* value > 20 ms have normal cardiac function while the prevalence of myocardial dysfunction and arrhythmias increases as a consequence of cardiac iron overload (T2* < 20 ms). A previous study comparing cardiac iron overload in transfusion dependent thal.m and SCD patients matched for age and liver iron content, found abnormally low cardiac T2* values (<20 ms) in nearly 40% of patients with thal.m, while the T2* values were normal in the patients with SCD (1) (Blood:103;1934, 2004). The purpose of the present study was to quantify iron content (T2* values) in the liver, heart and pancreas of multitransfused patients with sickle/β-thal. Patients and Methods: Eleven patients with sickle/β-thal., 3 males and 8 females, mean age 31 years ± 9.5 (SD) were analyzed, 6 of them were splenectomized. Their mean ± SD values for hemoglobin was 9.0 gr/dl, for serum ferritin - 3900 ng/ml ± 3944 and for transferrin saturation - 80% ± 23. All of them were transfused and received a mean of 97 packed cell units ± 88 (SD). Only one patient received iron chelation for 10 months until 6 months prior to entering the study. Seven patients received regularly Hydrea 1–1.5 gr/day for > 10 years. MRI evaluation (1.5T, GE MRI system) included: Left ventricular (LV) function (ejection fraction)- steady-state free procession (SSFP) cine sequence as well as iron load quantification- breath-hold multi echo gradient echo T2*, sampled across regions of interest in the LV septum, liver parenchyma and pancreatic tissue. (Eur. Heart J22:2171, 2001) Results: All patients had normal T2* values in the heart (>20ms) and in the pancreas (>30ms). The left ventricular ejection fraction, left ventricular endsystolic and endiastolic volumes (evaluated both by echo-cardiography and by cine function MRI) were normal in all patients. There was no evidence for pleural or pericardial effusion. The diameter of the pulmonary artery and right ventricle were normal. Seven patients demonstrated evidence of mild to moderate iron deposition in the liver (T2* <6.3 ms). In these patients mean serum ferritin (5656 ng/ml) and transferrin saturation (92.4%) were significantly higher (p=0.001) than in 4 patients with normal T2* levels in the liver (>6.3ms) where mean serum ferritin was 872ng/ml and transferrin saturation 59.5%. Conclusion: The T2* MRI values of 11 patients with sickle/β-thal. showed that whereas 7 patients had a certain degree of iron deposition in the liver, none demonstrated cardiac or pancreatic iron deposition. Therefore, with respect to iron deposition, multitransfused patients with sickle/β-thal. are similar to patients with homozygous SCD and not to patients with thal.m and thal intermedia. The reasons for this observation are still unclear. This similarity could be related in part to the relativly low number of transfusions, starting later in life, of patients with homozygous SCD or sickle/β- thal. compared to patients with thal.m. (1) The liver is the dominant iron storage organ and iron liver concentration correlates closely with the total body iron content. While iron uptake by hepatocytes is predominately mediated via transferrin and correlates with serum ferritin levels, as confirmed in the present study, this is not the case in regulation of cardiac and endocrine iron uptake. These organs might acquire the excess metal differently. It is possible that additional and/or different forms of iron, which have been identified, such as non-transferrin bound iron and labile plasma iron, are involved in determining iron loading in the heart and endocrine glands and/or because regulation of iron entry into the plasma by hepcidin might differ. Additional studies are in progress to address these issues.

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T2* MRI in Hypertransfused Children with Thalassemia Intermedia: Serum Ferritin Does Not Reflect the Reality

Blood ◽

10.1182/blood.v118.21.5304.5304 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5304-5304

Author(s):

Surekha Tony ◽

Shahina Daar ◽

Shoaib Al Zadjali ◽

Murtadha K. Al-Khabori ◽

Mohammed El Shinawy ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Conflicts Of Interest ◽

Iron Deposition ◽

Hepatic Iron ◽

Thalassemia Intermedia ◽

Hepatic Iron Overload ◽

T2 Mri ◽

Beta Gene ◽

Group 1

Abstract Abstract 5304 Background: Non-transfused patients with thalassemia intermedia (TI) accumulate iron in their body due to increased gastrointestinal absorption of iron and release of iron from the macrophages. Earlier studies have revealed that serum ferritin does not reflect the severity of iron overload in non-transfused TI patients. The current study aims at evaluating the iron overload status in a group of young hypertransfused TI children. Materials and Methods: Eleven patients (mean age 13.18±4.094 years) with TI on regular follow-up at the Pediatric Thalassemia Day Care Centre, Sultan Qaboos University Hospital, Oman were included in the study after approval by the Medical Research and Ethics Committee. All patients had beta gene mutational analysis. They were diagnosed as intermedia because of their definitive TI mutation, late age at presentation (>5 years) and transfusion independence (mean baseline Hb 6.9 g/dl). Patients were treated conventionally with hypertransfusion, and chelation, as guided by their serum ferritin levels. Serum ferritin (2 monthly) was analyzed using the Beckman Coulter Access 2 Immunoassay System. Based on serum ferritin levels, patients were classified into 2 groups, group 1(six patients) and 2 (five patients) with serum ferritin levels below and above 1000 ng/ml respectively. All patients underwent cardiac T2* MRI assessment. Based on local reference values for T2*MRI, quantification of cardiac iron deposition was categorized as normal, mild, moderate and severe iron overload at values > 20 ms, 14–20 ms, 10–14 ms and < 10 ms respectively. Simultaneous liver iron T2* values were categorized into normal, mild, moderate and severe iron overload at values > 9.1 ms, 7.1–9.0 ms, 3.1– 7.0 ms and <3.0 ms respectively. Results: Patients in group 1 and 2 had mean serum ferritin levels of 817.300±244.690 ng/ml and 1983.80±662.862 ng/ml respectively (p = 0.003). Despite this very high variation in serum ferritin values, T2* MRI showed comparable hepatic iron overload status in both the groups with mean hepatic T2* value of 2.51±0.46 ms and 3.4±1.63 ms in group 1 and group 2 respectively. The difference in hepatic T2* between the 2 groups is −0.88 (95% confidence interval −2.44 to 0.68) which is statistically insignificant (p =0.23, t-test). None of the studied patients had myocardial iron deposition (overall mean 36.86±7.8 ms). Other confounders like initial ages at presentation, pre-transfusion hemoglobin levels, durations of transfusion and chelation therapies were statistically insignificant for the 2 groups. No specific pattern of beta gene sequence was noted in either group. Conclusions: We conclude in our patients with TI on hypertransfusion, serum ferritin does not reflect their moderate to severe hepatic iron overload status. Inspite of steady serum ferritin trends, evaluation of iron overload by T2* MRI and optimal chelation is strongly recommended in hypertransfused TI patients. Disclosures: No relevant conflicts of interest to declare.

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