Jadenu Substituting Exjade in Beta Thalassemia Major (BTM) Patients with Iron Overload: Effect on Serum Ferritin Concentration, Liver Iron Content and Biochemical Profiles

Abstract Thalassemia major (TM) requires chronic blood transfusions ultimately cause iron overload and subsequently end-organ damage unless corrected. Iron chelation has been proven to decrease organ dysfunction and improve survival in transfusion-dependent β-thalassemia. However, taking iron chelation therapy every day has sometimes been a challenge in patients. Deferasirox is a once-daily, oral iron chelator that developed out of a need for a long-acting chelator. The approved mode of administration requires taking deferasirox on an empty stomach with water, apple juice, or orange juice to limit variation in bioavailability. This required administration schedule might not be palatable for patients. Additionally, approximately one-quarter of patients experience mild to moderate gastrointestinal symptoms, which may pose additional challenges. Jadenu is a new oral formulation of Exjade tablets for oral suspension. While Exjade is a dispersible tablet that must be mixed in liquid and taken on an empty stomach ,Jadnu can be taken in a single step, with or without a light meal, simplifying administration of treatment and allows greater convenience and may be associated with fewer gastrointestinal side effects versus the original formulation. This may significantly improve compliance. In addition, the new formulation may be associated increased bioavailability. Jadenu is 36% more bioavailable than the original formulation, Exjade®. Therefore, to convert from Exjade to Jadenu the dose of Jadenu should be about 30% lower, rounded to the nearest whole tablet. To date, the new formulation of deferasirox has only been evaluated in pharmacokinetic studies in healthy volunteers. No clinical data are available yet in patients taking this formulation. The objective of this study was to compare the effect of Jadenu substituting Exjade on serum Ferritin concentration, liver iron content and biochemical profile in (BTM) patients with iron overload. Patients and Methods: Twelve adult patients with BTM were studied. All patients were on regular packed cell transfusion therapy monthly to keep their Hb not less than 9 g/dl before transfusion. They were on Exjade therapy (30 mg/kg per day) for 5 years or more before changing them to Jadenu therapy (14-28mg/kg/day). We evaluated Serum ferritin and the liver iron (LIC) measured by the Ferriscan method. Investigations included measuring hepatic functions (alanine transferase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP) and albumin) , creatinine and fasting blood glucose (FBG) every clinic visit (q 3 months). In addition thyroid function (free T4 (FT4), thyrotropin (TSH), 25 OH vitamin D and PTH levels were measured before and one year after starting Jadenu therapy. Patients were monitored for gastrointestinal and other reported side-effects related to the drugs. All patients were on vitamin D 800 U/day and folic acid 5 mg / day. Paired t student test was used to compare lab results before versus after Jadenu treatment. Linear regression equation was used to investigate possible relation between variables. Results A year after treating patients with Jadenu serum ALT decreased (non-significant) but there was no significant change in circulating concentrations of creatinine, albumin, ALP or FBG. (Table 1) Apart from some gastrointestinal complaints reported in 3 patients that did not require discontinuation of therapy, patients did not have any other side effects. There was a non-significant decrease in LIC and ferritin levels after 1 year of using Jadenu. Thyroid and parathyroid hormone did not change during Jadenu therapy. (Table 2) A positive significant correlation was found between serum ferritin level and LIC measured by ferriscan method. LIC and serum ferritin level were correlated significantly with ALT level ( r = 0.31 and 0.45 respectively, p < 0.05) . No significant correlation was detected between LIC and other biochemical or hormonal levels. This study showed that the use of Jadenu after Exjade was associated with non-significant decrease in liver iron and ALT. There was no change in FBG, creatinine albumin or thyroid function. No side effects required discontinuation of the medicine. Conclusion: Jadenu is more palatable and improve quality of life for patients with BTM, however it was associated with minimal decrease in LIC and ALT level suggesting marginal improvement of iron chelation probably due to easier administration. Disclosures No relevant conflicts of interest to declare.

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SEVERE LIVER IRON CONCENTRATIONS (LIC) IN 24 PATIENTS WITH Β-THALASSEMIA MAJOR: CORRELATIONS WITH SERUM FERRITIN, LIVER ENZYMES AND ENDOCRINE COMPLICATIONS

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2018.062 ◽

2018 ◽

Vol 10 ◽

pp. e2018062 ◽

Cited By ~ 3

Author(s):

Vincenzo De Sanctis

Keyword(s):

Iron Overload ◽

Adrenal Insufficiency ◽

Serum Ferritin ◽

Chelation Therapy ◽

Ferritin Level ◽

Iron Chelation ◽

Dry Weight ◽

Thalassemia Major ◽

Liver Iron

Abstract. Introduction: Chronic blood transfusion is the mainstay of care for individuals with β-thalassemia major (BTM). However, it causes iron-overload that requires monitoring and management by long-term iron chelation therapy in order to prevent endocrinopathies and cardiomyopathies, that can be fatal. Hepatic R2 MRI method (FerriScan®) has been validated as the gold standard for evaluation and monitoring liver iron concentration (LIC) that reflects the total body iron-overload. Although adequate oral iron chelation therapy (OIC) is promising for the treatment of transfusional iron-overload, some patients are less compliant with it and others suffer from long-term effects of iron overload. Objective: The aim of our study was to evaluate the prevalence of endocrinopathies and liver dysfunction, in relation to LIC and serum ferritin level, in a selected group of adolescents and young adult BTM patients with severe hepatic iron overload (LIC from 15 to 43 mg Fe/g dry weight). Patients and Methods: Twenty-four selected BTM patients with severe LIC, due to transfusion-related iron-overload, followed at the Hematology Section, National Center for Cancer Care and Research, Hamad Medical Corporation of Doha (Qatar), from April 2015 to July 2017, were retrospectively evaluated. The prevalence of short stature, hypogonadism, hypothyroidism, hypoparathyroidism, impaired fasting glucose (IFG), diabetes, and adrenal insufficiency was defined and assessed according to the International Network of Clinicians for Endocrinopathies in Thalassemia (ICET) and American Diabetes Association criteria. Results: Patients have been transfused over the past 19.75 ± 8.05 years (ranging from 7 to 33 years). The most common transfusion frequency was every 3 weeks (70.8%). At the time of LIC measurements, the mean age of patients was 21.75 ± 8.05 years, mean LIC was 32.05 ± 10.53 mg Fe/g dry weight (range: 15 to 43 mg Fe/g dry weight). Their mean serum ferritin level was 4,488.6 ± 2,779 µg/L. The overall prevalence of growth failure was 26.1% (6/23), IFG was 16.7% (4/24), sub-clinical hypothyroidism was 14.3% (3/21), hypogonadism was 14.3% (2/14), diabetes mellitus was 12.5% (3/24), and biochemical adrenal insufficiency was 6.7% (1/15). The prevalence of hepatitis C positivity was 20.8% (5/24). No case of clinical hypothyroidism, adrenal insufficiency or hypoparathyroidism was detected in this cohort of patients. The prevalence of IFG impaired fasting glucose was significantly higher in BTM patients with very high LIC (>30 mg Fe/g dry liver) versus those with lower LIC (p = 0.044). LIC was correlated significantly with serum ferritin levels (r = 0.512; p = 0.011), lactate dehydrogenase (r = 0.744; p = 0.022) and total bilirubin (r = 0.432; p = 0.035). Conclusions: A significant number of BTM patients, with high LIC and endocrine disorders, still exist despite the recent developments of new oral iron chelating agents. Therefore, physicians’ strategies shall optimize early identification of those patients in order to optimise their chelation therapy and to avoid iron-induced organ damage. We believe that further studies are needed to evaluate if serial measurements of quantitative LIC may predict the risk for endocrine complications. Until these data are available, we recommend a close monitoring of endocrine and other complications, according to the international guidelines.

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LONGITUDINAL STUDY ON LIVER FUNCTIONS IN PATIENTS WITH THALASSEMIA MAJOR BEFORE AND AFTER DEFERASIROX (DFX) THERAPY

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2014.025 ◽

2014 ◽

Vol 6 (1) ◽

pp. e2014025 ◽

Cited By ~ 5

Author(s):

Ashraf Tawfik Soliman ◽

Mohamed Yassin ◽

Fawzia AlYafei ◽

Lolwa Al-Naimi ◽

Noora Almarri ◽

...

Keyword(s):

Liver Function ◽

Iron Overload ◽

Serum Ferritin ◽

Negative Correlation ◽

Ferritin Level ◽

Iron Chelation ◽

Thalassemia Major ◽

Growth Potential ◽

Igf I ◽

Liver Functions

With regular blood transfusion and iron chelation therapy, most patients with thalassemia major (BTM) now survive beyond the third decade of life . Liver disease is becoming an important cause of morbidity and mortality in these patients. Chronic hepatitis and/or severe iron overload are important causes of liver pathology. Iron chelation with desferrioxamine (Desferal) reduces excessive body iron, but its efficacy is limited by poor compliance and dose related toxicity. The recent use of Deferasirox (Exjade- DFX ), an oral single dose therapy has improved the compliance to chelation therapy.Aims: To study the long-term liver functions in BMT patients, seronegative for liver infections before versus after DFX therapy in relation to ferritin level and IGF-I level.Methods: Liver function tests including: serum bilirubin, alanine transferase (ALT), aspartate transferase (AST) , albumin, insulin-like growth factor – I (IGF-I) and serum ferritin concentrations were followed every 6 months in 40 patients with BTM, with hepatitis negative screening (checked every year), for at least five years of DFO therapy and 4-5 years of DFX therapy .Results: DFX therapy (20 mg/kg/day) significantly decreased serum ferritin level in patients with BTM, this was associated with significant decrease in serum ALT, AST, ALP and increase in IGF-I concentrations. Albumin concentrations did not change after DFX treatment. ALT and AST levels were correlated significantly with serum ferritin concentrations ( r = 0.45 and 0.33 respectively , p < 0.05) . IGF-I concentrations were correlated significantly with serum ALT (r= 0.26, p = 0.05) but not with AST, ALP, bilirubin or albumin levels.The negative correlation between serum ferritin concentrations and ALT suggests that impairment of hepatic function negatively affects IGF-I synthesis in these patients due to iron toxicity, even in the absence of hepatitis.Conclusions: Some impairment of liver function can occur in hepatitis negative BMT patients with iron overload. The use of DFX was associated with mild but significant reduction of ALT, AST and ALP and increase in IGF-I levels. The negative correlation between IGF-I and ALT concentrations suggest that preventing hepatic dysfunction may improve the growth potential in these patients.

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Iron Overload and Haematopoiesis in MDS: Does Blood Transfusion Promote Progression to AML?

Blood ◽

10.1182/blood.v112.11.2685.2685 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2685-2685 ◽

Cited By ~ 7

Author(s):

Lap Shu Alan Chan ◽

Rena Buckstein ◽

Marciano D. Reis ◽

Alden Chesney ◽

Adam Lam ◽

...

Keyword(s):

Bone Marrow ◽

Dna Damage ◽

Iron Overload ◽

Serum Ferritin ◽

Chelation Therapy ◽

Bone Marrow Cells ◽

Ferritin Level ◽

Iron Chelation ◽

Iron Chelation Therapy ◽

Ferritin Concentration

Abstract Introduction: The biology of myelodysplastic syndrome (MDS) is poorly understood, and treatment options are limited. Thus, most MDS patients require chronic red blood cell transfusion, and many develop secondary iron overload. Although the pathophysiological consequences of iron overload to the heart, liver, and endocrine organs have been well characterized, its effects on haematopoiesis have not been studied. However, it has been observed that chelation therapy in iron-overloaded MDS patients may result in reduction of transfusion requirements, and recent studies have suggested a correlation between the use of iron chelation therapy and improvement in leukaemia-free survival in MDS. At the cellular level, iron toxicity is mediated in large part via the generation of reactive oxygen species (ROS). It has been shown in animal models that accumulation of ROS leads to senescence of haematopoietic stem cells, and that ROS cause DNA damage and promote the development of malignancy. These effects of ROS may be particularly important in MDS, in which haematopoiesis is already severely compromised and genetic instability is a striking feature. Hypothesis: We hypothesize that iron overload secondary to transfusion leads to increased levels of intracellular ROS in early haematopoeitic cells in MDS. The increase in intracellular ROS in MDS would be predicted to lead further impairment of haematopoiesis via stem cell exhaustion and while promoting accumulation of DNA damage by myelodysplastic stem cells and early progenitors, thus accelerating progression of MDS to acute leukaemia. Results: To test this hypothesis, we examined the relationship between transfusion-related iron overload and ROS content of CD34+ bone marrow cells in MDS. ROS content was measured in CD34+ cells by flow cytometry in bone marrow aspirates from 34 consecutive MDS patients (CMML=4, MDS/MPD=2, RA=4, RARS=3, RCMD=2, RAEB 1=6, RAEB 2=12, RAEB-t/AML=1). The patients represented a wide range of prior transfusion burden (0->300 units PRBC) and serum ferritin levels (11->10000 μg/L). ROS was strongly correlated with serum ferritin concentration for patients with iron overload (serum ferritin >1000 μg/L; n=14, R=0.733, p<0.005). The correlation between ROS and ferritin level was even stronger in the subset of patients with RAEB 1 or RAEB 2 and iron overload (n=11, R=0.838, p<0.005). In contrast, no correlation between ROS and ferritin level was demonstrated for patients with serum ferritin <1000 μg/L (n=20). Importantly, iron chelation therapy was associated with a reduction in CD34+ cell ROS content in one patient. To assess the effect of iron overload on normal stem cell and progenitor function, we established a mouse model of subacute bone marrow iron overload. B6D2F1 mice were loaded with iron dextran by intraperitoneal injection (150mg total iron load over 21 days), and sacrificed three days after the end of iron loading. Iron staining of tissue sections confirmed iron deposition in the bone marrow, liver, and myocardium. The development of splenomegaly was noted in iron-loaded animals. Flow cytometric analysis revealed increased apoptosis of bone marrow cells in iron loaded mice based on annexin V+/7 AAD-staining (6.26±0.96% versus 3.54±0.99% for control mice, paired student’s t-Test p<0.005). However, ROS content in CD117+ progenitors of iron loaded mice was similar to control mice. Thus, subacute iron loading in mice increases apoptosis but does not alter the ROS content of HSCs; we postulate that chronic iron overload is required to achieve this effect. Conclusions: These results establish a relationship between CD34+ cell ROS content and serum ferritin concentration in MDS patients with iron overload, and indicate that iron chelation therapy in this patient population reverses this ROS accumulation. The physiological consequences of this relationship are currently being investigated in this patient set by haematopoietic colony assays and assessment of DNA damage in CD34+ cells. Nonethelesss, these data may have key implications for the deployment of iron chelation therapy in MDS patients, and may explain the association between the use of iron chelation and improved leukaemia-free survival in MDS.

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Serum Metabolite Profiles Are Reflective of Iron Overload in Thalassemia Major Patients on Chelation Therapy

Blood ◽

10.1182/blood.v118.21.2112.2112 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2112-2112

Author(s):

Farzana Sayani ◽

Niloufar Abdolmohammadi ◽

Anne Marie Lauf ◽

Aalim Weljie

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Cardiac Mri ◽

Chelation Therapy ◽

Thalassemia Major ◽

Multivariate Regression Analysis ◽

Liver Iron ◽

Liver Iron Content ◽

Metabolic Systems ◽

Metabolite Profiles

Abstract Abstract 2112 Introduction: Iron overload (IO) either through blood transfusions or increased gastrointestinal absorption is associated with organ dysfunction and increased morbidity and mortality in patients with various hematological disorders including thalassemia. Despite improved methods of iron load detection and chelation therapy, patients still continue to be at risk for iron-associated toxicities. Methods for predicting IO include serum ferritin, liver iron content by MRI, and cardiac MRI T2*. Limited information is available regarding the effects of IO on the different metabolic systems in the liver and heart, which may change with chelation therapy. Different chelators, including deferoxamine (DFO), deferiprone (DFP) and deferasirox (DFX), chelate iron at different rates and effectiveness from the liver and heart. The liver is involved in maintenance of glucose and lipid homeostasis, and iron-triggered injury increases secondary metabolites including triacylglycerols and glucose. IO alters the stability of hepatic and myocardial lysosomal membranes releasing higher levels of lysosomal enzymes in liver compared to heart in animal models. These and other metabolic pathways have not been studied extensively in iron-overloaded patients. The new technology of metabolomics allows for the concurrent measurement and analysis of multiple metabolites and has the potential to provide more valuable information on the metabolic systems affected by iron overload that could have clinical relevance. Aim: To determine if novel metabolomics technologies can identify specific metabolites and pathways affected by iron overload including energy, carbohydrate, and lipid metabolism. Methods: In this pilot project, we included twelve iron overloaded patients (thalassemia major N=7, thalassemia intermedia N=2, hemoglobin H disease N=2, pure red cell aplasia N=1) (age > 18 years) and 12 sex and age-matched controls. Clinical parameters including age, sex, chelator therapy, pre-transfusion hemoglobin, serum ferritin, liver iron content, and cardiac MRI T2* were collected on patient samples. The metabolite profile on fasting serum samples was analyzed in triplicate using gas chromatography-mass spectrometry (GC-MS) along with MetaboliteDetector a software. Significant metabolites were identified using multivariate regression analysis by supervised projection methods (two-way orthogonal partial least squares discriminant analysis, O2PLS-DA) using Simca-P (Umetrics). Results: A total of 291 analytes were detected and quantified for each samples by GC-MS metabolomics. Clear differences were detected in serum metabolite profiles between patients with iron overload and control samples (p = 0.03) (Figure 1). Metabolite differences between the two groups consisted of amino acids, their breakdown products, and sugars. Multivariate regression analysis showed correlation between the different metabolite profiles and diagnosis of thalassemia major (p = 0.02). No significant differences were seen comparing age, sex, pre-transfusion hemoglobin, serum ferritin, LIC, and cardiac MRI T2*. There was a non-significant but detectable difference observed in the metabolic profile of the 3 patients on combination therapy with DFO and DFP (p<0.3) suggesting possible differences related to the presence DFP. Conclusion: We conclude that metabolomics is a valid and useful tool to detect differences in the iron-associated metabolic changes in iron overloaded patients, specifically, thalassemia major. Combination therapy with DFO and DFP has a possibly different metabolic profile compared to other chelators. Further work is needed to delineate the specific metabolic changes due to iron chelation, specifically, effects on oxidative damage, as chelation therapy is known to reduce the levels of non-transferrin bound iron and reactive oxygen species. A larger sample size may also be needed to further detect any metabolite differences in relation to organ iron load. Disclosures: No relevant conflicts of interest to declare.

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Monitoring Cardiac Siderosis in Patients with Beta-Thalassemia Major on Various Chelation Regimens,

Blood ◽

10.1182/blood.v118.21.3177.3177 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3177-3177

Author(s):

Srikanth R. Ambati ◽

Rachel Randolph ◽

Kevin Mennitt ◽

Dorothy A Kleinert ◽

Patricia Giardina

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Iron Concentration ◽

Iron Chelation ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Liver Iron ◽

Beta Thalassemia Major ◽

Cardiac Siderosis ◽

Hepatic Iron Overload

Abstract Abstract 3177 Background: Patients with Beta-thalassemia major develop progressive iron overload in various organs. Cardiac siderosis is a major cause of mortality and morbidity in these patients, and also poses a significant treatment challenge. Methods: We have reviewed 101 beta-thalassemia major patients 39 Male (M) 62 Female (F) with a mean age of 27.9 (range: 2 to 60 years). All received regular transfusions to maintain pre transfusion Hb levels of 9 to10 gm/dl and all received iron chelation initially with deferoxamine (DFO) and subsequently treated with deferasirox (DFX) or deferiprone (DFP) in combination with DFO. Each patient was monitored yearly for iron excess by hepatic and cardiac magnetic resonance imaging (MRI) T2*. They were also assessed with monthly evaluations for liver and renal function (Bili, AST, ALT, BUN, Creatinine), serum ferritin, CBC (or weekly if on DFP), and urinalysis. Annual EKG, ECHO, hearing and vision testing and endocrine evaluations were also performed. The patients were grouped according to the severity of cardiac siderosis. Mild to moderate cardiac siderosis was defined as a T2* 12–20 msec and severe cardiac siderosis T2*≤ 11 msec. Annual studies were compared using paired student T test and repeated measures Analysis Of Variance (ANOVA) when necessary. Patient population: Twenty one of the 101 patients (7M and 14F) with a mean age of 30.6 yr, age range 15 to 56 yr, had abnormal cardiac T2* of <20 msec and three or more subsequent annual cardiac T2* measurements. Thirteen patients, 3 M 10 F with a mean age of 33 (range: 19 to 60), had severe cardiac siderosis and 8 patients, 3 M 5 F with mean age of 38 (range: 25 to 49), had mild-moderate cardiac siderosis. During the course of the observation their iron chelation therapy was optimized to reduce serum ferritin levels < 1500 μg/dl and to reduce or maintain liver iron concentration (LIC) ≤ 7 mg/gm dw. Data analysis: At the time of their first annual MRI study (baseline), 8 patients were on DFO of which 6 were switched to DFX, 13 patients were on DFX, 11 patients were dose escalated on DFX, and 4 patients were switched to combination chelation with DFO and DFP. At baseline, patients with severe cardiac siderosis had a mean cardiac T2* level = 7.4 ± 0.47 SEM (range: 4.6 to 11msec). Over the treatment course of 6 years annual cardiac T2* levels consistently improved and by 6 years cardiac T2* reached a mean level =14.3 ±1.5 SEM (range: 12 to 17 ms) (Fig 1). Those patients who at baseline had a mild to moderate cardiac siderosis with mean cardiac T2* of 14.6 ± 1.02 SEM (range: 12 to 19 msec) improved by 3 years of treatment when they achieved a mean cardiac T2* of 26.3 ± 3.4 SEM (range of 16 to 42 msec) (Fig 2). Liver iron concentration (LIC) was measured annually by MRI. Initially the majority, 16 out of 21 of patients, had hepatic iron overload LIC ≤ 10 mg/ gm dw of whom 56% (9 of the 16) had severe cardiac siderosis. 5 of 21 patients had a LIC > 15 mg/ gm dw of whom 80% (4 out of 5) patients had severe cardiac siderosis (Fig 3). Patients with LIC ≤10 mg/ gm dw had ferritin levels ranging from 166 to 3240 μg/ dl and patients with LIC >15 mg/ gm dw had elevated serum ferritin levels of 1180 to 17,000 μg/ dl. Patients with severe cardiac siderosis had mean MRI ejection fraction (EF)= 55.8% (range: 31 to 70%) while patients with mild to moderate cardiac siderosis had mean MRI EF= 60% (range: 53 to 66%). One patient with severe cardiac siderosis was recovering from symptomatic congestive heart failure. Conclusion: Cardiac siderosis can be noninvasively diagnosed utilizing MRI T2* techniques and subsequently to monitor treatment. The majority of patients improve cardiac T2* over time with optimal chelation therapy. Severe cardiac siderosis occurs even with mild to moderate hepatic iron overload. Left ventricular EF may not predict severe cardiac siderosis. Therefore it is important to annually monitor cardiac siderosis with MRI T2*. Disclosures: No relevant conflicts of interest to declare.

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LIVER IRON CONTENT (LIC) IN ADULTS WITH NON-TRANSFUSION DEPENDENT SICKLE CELL DISEASE (NT-SCD). CORRELATION WITH SERUM FERRITIN AND LIVER ENZYMES CONCENTRATIONS

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2017.037 ◽

2017 ◽

Vol 9 (1) ◽

pp. 2017037 ◽

Cited By ~ 3

Author(s):

Vincenzo De Sanctis

Keyword(s):

Serum Ferritin ◽

Iron Content ◽

Serum Ferritin Level ◽

Ferritin Level ◽

High Serum ◽

Liver Iron ◽

Ferritin Concentration ◽

Liver Iron Content ◽

Serum Ferritin Concentration ◽

High Liver

Abstract. Introduction: Sickle cell disease (SCD) is an important cause of morbidity and mortality worldwide, causing damage and dysfunction in multiple organs. The complications of this disease are numerous, affect every organ and/or tissue in the body and vary considerably among patients over the time which challenge its management. Aim of our study: To determine the iron status of 17 patients with NT-SCD patients and 6 patients with TD- SCD using both serum ferritin level (SF ) and Ferriscan® evaluation of liver iron content (LIC) and correlate values of LIC on the one hand with SF levels and some hepatic functions (ALT, AST, ALP and albumin). Results: 17 adults with NT-SCD (n = 17, age: 32±15 years) were studied. Seven of NT-SCD had serum ferritin > 500 μg/L, 4 out of the seven had high liver iron measured by FerriScan® (> 30 mg/kg/ tissue dry weight - DW). Two patients had high liver iron content despite a concomitant serum ferritin concentration < 500 μg/L. Two patients had high serum ferritin (1.117 μg/L and 675 μg/L) while their LIC was normal (< 30 mg/kg/DW). 5 patients had elevated ALT and/or AST concentrations. In TD-SCD (n = 6, age = 25 ±11 years), 2 patients had serum ferritin <500 μg/L, one of them had high LIC (127 mg/kg/DW). Liver enzymes were high in two patients. Serum ferritin concentration was correlated significantly with LIC (r = 0.85, p < 0.001). Neither serum ferritin level, nor LIC was correlated significantly with hepatic enzyme levels. Conclusions: A significant number of our patients with ND-SCD had high LIC , high serum ferritin and elevated hepatic enzymes (ALT and AST). Despite some limitations of our study (small NT-SCD cohort), these findings have important clinical implications. We recommend to measure serum ferritin and LIC in NT-SCD patients to apply therapeutic preventive measures with iron chelation therapy in patients with high LIC.

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Variables associated with malondialdehyde level in thalassemia major patients

Paediatrica Indonesiana ◽

10.14238/pi52.3.2012.125-31 ◽

2012 ◽

Vol 52 (3) ◽

pp. 125

Author(s):

Arum Gunarsih ◽

Pustika Amalia ◽

Imam Boediman

Keyword(s):

Oxidative Stress ◽

Vitamin E ◽

Iron Overload ◽

Serum Ferritin ◽

Medical Records ◽

Serum Ferritin Level ◽

Ferritin Level ◽

Iron Chelation ◽

Thalassemia Major ◽

Indirect Measurement

BackgmundThalassemia is the most cormnon hereditary haemolyticanaemia in the world, including in Indonesia. The main treatmentfor thalassemia is regular transfusions, but these are knO\vn to causeiron overload. Moreover, iron overload in jJ􀁮thalassemia patientsgenerates oxygen free radicals and peroxidative lipid injury. Ferritinserum concentration is used as indirect measurement of iron overload.Malondialdehyde (MDA), a terminal compound oflipid peroxidation,is used as an index of oxidative stress status.Objective To assess the correlation between iron overload (serumferritin level) and MDA as a marker of oxidative stress in thalassemiamajor patients.Methods This c ross􀁮sectional study was conducted at CiptoMangunkusumo Hospital, Jakarta, from May􀁮June 2009. Subjectswere thalassemia major patients (homozygous jJ􀁮thalassemia orjJ􀁮thalassemia;HbE) who received regular blood transfusions, iron􀁮chelation, and vitamin E as an antioxidant. Data was collected by his􀁮tory􀁮taking, physical examination, medical records, and questionnaires.Blocd specimens were dra\Vll from the thalassemia major subjects beforetransfusion and examined for serum ferritin and MDA levels.Results Fifty􀁮five subjects Mth thalassemia major (34 homozygousjJ􀁮thalassemia and 21 jJ􀁮thalassemia;HbE) were included in ourstudy. Mean serum ferritin level was 3693.2 (SD 21423),ug/L andme811 MDA level was 0.641 (SD 0.283) nmolimL. No cor relationwas found between serum ferritin and MDA levels in thalassemiamajor subjects (r=0.147, P=0.285). As additional results, this studyalso showed no correlation between MDA to reguler vitamin Econsumption (r=0.277, P=0.028) as well as MDA and nutritionalstatus (F0371, P􀁯0.()J4).Conclusion There was no cor relation between serum ferritin leveland plasma MDA level in thalassemia major subjects, no cor relationsbetween MDA and regular vitamin E consumption, as well as MDAand nutritional status. [paediatr Indones. 2012;52:125,31].

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Lack of Correlation between Serum Ferritin and Liver Iron Concentration in Beta-Zero Thalassemia Intermedia.

Blood ◽

10.1182/blood.v104.11.3620.3620 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3620-3620 ◽

Cited By ~ 1

Author(s):

Renzo Galanello ◽

Nicolina Giagu ◽

Susanna Barella ◽

Liliana Maccioni ◽

Raffaella Origa

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Regulatory Protein ◽

Iron Concentration ◽

Iron Chelation ◽

Dry Weight ◽

Thalassemia Major ◽

Thalassemia Intermedia ◽

Liver Iron Concentration ◽

Liver Iron

Abstract Serum ferritin and liver iron concentration (LIC) are the most commonly used methods for assessment of iron overload in thalassemia. While in patients with thalassemia major a significant correlation has been found between these two parameters, data are lacking in patients with thalassemia intermedia. In this study we measured the serum ferritin and LIC in 22 adult patients with beta-zero thalassemia intermedia never transfused (14 patients) or sporadically transfused, i.e. less than 10 units in total (8 patients), who maintained a mean hemoglobin of 8.8 ± 1.1 g/dl. Serum ferritin levels were measured by an automated chemiluminescence immunoassay analyzer, whereas LIC was determined by atomic absorption in liver biopsies. We compared the results obtained in those patients with those obtained in 22 regularly transfused (mean annual Hb = 11.3 ± 0.3 g/dl) and iron chelated thalassemia major patients, matched by sex, age and liver iron concentration. We also determined serum erythropoietin (s-epo) and serum transferrin receptor (s-TfR) in a cohort of the two patient groups (12 thalassemia intermedia; 15 thalassemia major). Mean LIC was 11.3 ± 6 mg/g dry weight tissue in thalassemia intermedia, and 11.8 ± 7 mg/g d.w. in thalassemia major group. Mean serum ferritin (at least 2 determinations from each patient within ± 2 months of liver biopsy) was 627 ± 309 ng/ml in thalassemia intermedia and 2748 ± 2510 ng/ml in thalassemia major. The difference was statistically significant (p = 0.0001). LIC was weakly correlated with serum ferritin in thalassemia major patients (r2=0.46; p=0.001) and uncorrelated in patients with thalassemia intermedia (r2=0.04; p=0.37) (Figure). S-epo and s-TfR were significantly higher in thalassemia intermedia than in thalassemia major [s-epo 467 ± 454 mU/ml versus 71 ± 44 mU/ml (p<0.001); s-TfR 43 ± 13 mU/ ml versus 13 ± 6 mU/ml (p<0.0001)]. The discrepancy between LIC and serum ferritin in thalassemia intermedia patients may be due to the higher levels of s-epo (secondary to anemia) in those patients, which through the iron regulatory protein 1 determine an up-regulation of s-TfR and a repression of ferritin translation (Weiss et al 1997). The mechanism of iron overload may also be mediated by hepcidin, whose synthesis could be suppressed as a consequence of anemia. The observation reported has important implications for iron chelation in patients with thalassemia intermedia. In such patients serum ferritin levels have little value for the monitoring of iron overload. Figure Figure

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Reduction of Liver Iron Load in Adult Patients with β-Thalassemia Major Treated with Modern Chelation Modalities

Folia Medica ◽

10.3897/folmed.62.e39518 ◽

2020 ◽

Vol 62 (2) ◽

pp. 265-270

Author(s):

Pencho G. Georgiev ◽

Katya G. Sapunarova ◽

Veselina S. Goranova-Marinova ◽

Stefan E. Goranov

Keyword(s):

Iron Overload ◽

Ferritin Level ◽

Normal Liver ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Liver Mri ◽

Liver Iron ◽

Ferritin Concentration ◽

Female Ratio ◽

Beta Thalassemia Major

Background: Management of beta-thalassemia major (TM) requires life-long hemotransfusions leading to iron overload. Iron elimination is enhanced by the use of modern chelators.  Aim: To assess the effect of modern chelation therapy by dynamics of serum ferritin concentration and liver MRI T2*. Patients and methods: Forty-six patients with TM (male to female ratio =1:1, mean age 33.2±10.9 years) were prospectively studied between 2011 and 2014. Twenty-one patients (45.7%) were treated with deferasirox, 17 (37%) – with deferiprone, and 8 (17.3%) – with deferiprone in combination with deferoxamine. Ferritin was measured by ELISA. MRI T2* was assessed by Siemens Magnetom Avanto 1.5T. The patients were allocated into 3 groups based on their initial ferritin level and liver MRI T2*. Statistical analysis was performed using SPSS v. 18 for Windows. Data were analysed by descriptive analysis, analysis of variance and correlative analysis, means were compared using t-test and one-way ANOVA. Results: In 2011, 9 (19.5%) patients had normal liver MRI T2*; in 2014 they were 17 (37%). The patients with mild grade liver siderosis were 12 (26%) in 2011, and in 2014 they were 14 (30.4%). In 2011, the patients with moderate liver siderosis were 14 (30.4%), and in 2014 – 12 (26.0%). Eleven patients (23.9%) had severe liver siderosis in 2011 and only two patients (4.0%) were diagnosed with the condition in 2014. Conclusion: A reduction of iron overload was found in all studied groups. This positive effect is attributed to the use of modern chelators and the ease of access to accurate monitoring.

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