scholarly journals Some aspects of thyroid dysfunction in thalassemia major patients with severe iron overload

2011 ◽  
Vol 51 (2) ◽  
pp. 66
Author(s):  
Cynthia Rindang ◽  
Jose R. L. Batubara ◽  
Pustika Amalia ◽  
Hindra Satari
Keyword(s):  
Iron Overload ◽  
Chelation Therapy ◽  
Elevated Serum ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Primary Hypothyroidism ◽  
Iron Chelation Therapy ◽  
Free T4 ◽  
Cross Sectional ◽  
Female Ratio

Background Severe iron overload due to recurrent transfusions for chronic anemia and inadequate iron chelation therapy in thalassemia major patients result in various complications, including hypothyroidism. Currently, there has been no data on the prevalence of hypothyroidism in thalassemia major patients at the Thalassemia Centers, Department of Child Health, CiptoMangunkusumo Hospital (DCH CMH).Objective To study the prevalence of primary hypothyroidism in thalassemia major patients in the Thalassemia Center, DCH MCH.Methods We performed a cross-sectional, descriptive study. All thalassemia major subjects aged O􀁬18 years with severe iron overload underwent thyroid functionexamination. Primary hypothyroidism was defined as either normal (compensated) or decreased (decompensated) free T4 (FT4) levels, along with elevated sensitive thyroid􀁬stimulatinghonnone (TSH)levels. Results 179 subjects enrolled this study Mth male: female ratio of 1: 1.6. The prevalence of primary hypothyroidism in thalassemia majorpatients Mth severe iron overloadws26.8% (48/179). Of those 48,45 had compensated hypothyroidism and 3 had decompensated hypothyroidism, 25.1% and 1.7% of the total subjects, respectively. Compensated hypothyroidism was observed in 17 subjects aged ≤1O years and in 28 subjects aged> 10 years. All 3 decompensated hypothyroidism cases were> 10 years of age. No relationship was found between the occurrence of primary hypothyroidism and mean pre-tr811sfusion Hb levels (P=0.481, OR 1.30; 95% CI 0.63 to 2.68), elevated serum ferritin levels (P=0.74, OR 0.89; 95% CI 0.46 to 1.75), and compliance to iron chelation therapy (P=0.570, OR 0.76; 95% CI 035 to 1.65). Based on multivariate analysis, only age of <10 year-old (P=O.029, OR 0.469; 95% CI 0.23 to 0.93) was significantly associated Mth primary hypJthyroidism. Further analysis using receiver operator curve (ROC) technique found that age of 8.5 year-old was the cutoff value to predict the risk of hypothyroidism. Conclusion The prevalence of primary hypothyroidism in our study is high. The occurrence of hypothyroidism is associated with age.

Clinical Effectiveness of Iron Chelation Therapies in Syrian Patients with β Thalassemia Major: Suboptimal Clinical Outcomes and High Prevalence of Iron Overload

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1719-1719
Author(s):  
Youssef A Lama ◽  
Hanan Touma ◽  
Khawla AlKeba ◽  
Osama Maksoud
Keyword(s):  
Combination Therapy ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Clinical Effectiveness ◽  
Thalassemia Major ◽  
Iron Chelation Therapy ◽  
Ferritin Concentration ◽  
Therapeutic Outcomes ◽  
High Prevalence

Abstract Background Thalassemia is the most prevalent autosomal abnormality in the population of Syria. In 2013, the total number of registered thalassemia patients is 8300. Disease prevalence is reinforced by the high rate of consanguineous marriages especially in the rural regions of this Middle Eastern and Mediterraneancountry. Regular blood transfusions and iron chelation therapy (ICT) have significantly improved survival and reduced morbidity of patients withβ thalassemia major (BTM). Although ICTs are provided free of charge by the government to all (BTM) patients, adequate monitoring of therapeutic outcomes is lacking, and cardiac complications still represent significant morbidity and remain the leading cause of mortality. Objective This study aimed at evaluating the prevalence of poor chelation in Syrian patients with BTM, and assessing the effectiveness of different iron chelation regimens provided by the National Thalassemia Program. Methods We conducted a single-centered study encompassing two phases; i) a retrospective chart review of serum ferritin levels of all female and male patients (≥ 3y) with (BTM) receiving iron chelation regimens (mono- or combination therapy) in 2009 and 2010; and ii) a 15 month prospective observational study to evaluate the effectiveness of desferrioxamine (DFO) monotherapy (at a dose of 40-50 mg/kg given over 8–10 h on 5-7 d/week), versus DFO (at the same dose used for DFO monotherapy) in combination with deferiprone (DFP) (at a dose of 75 mg/kg/day) [DFO+DFP] in patients received prior monotherapy with DFO but had poor response. Endpoints were defined as reducing iron stores in iron overloaded patients and improving cardiac function assessed by left ventricular ejection measurements using Doppler Echocardiogram. Statistical analysis of data sets was performed using Prism Graphpad, version 5. Results A total of 493 records of all patients registered at the National Thalassemia Centre in Homs were evaluated. 280 (56.8%) of these patients were diagnosed with BTM, and 245/280 (87.5%) were receiving iron chelation therapy. The average age was 11.35 ± 5.69 year-old (mean ± SD), age range [3-32 year], and male-to-female sex ratiowas 102:103. 39% of the patients were administered DFO, 30% and 10% received oral deferasirox (DFX) and deferiprone (DFP) respectively, whereas 21% received a combination of [DFO + DFP]. The average ferritin concentration of the study population was 3954.89 ± 1431.37 [range from 1362 to 8656] ug/l in 2009, and 4038.22 ± 1572.49 [range from 1173 to 8210] ug/l in 2010. Strikingly, 98% of patients had iron overload; [15% mild, 35% moderate and 48% severe] in 2009, and [12.3% mild, 42.5% moderate and 45.2% severe] in 2010. Patients on DFX had the lowest ferritin concentrations when compared with these of their peers on the DFO and [DFO + DFP] regimens (P=0.0001 and P=0.02 respectively). Patients of DFX also had the lowest percentage of sever iron overload (31%) in comparison with 58%, 51%, and 40% in patients on DOF, [DFO+DFP], and DFP respectively. In the prospective observational phase of our study, several comparative assessments were conducted. The combination of [DFO+DFP] reduced ferritin concentration by 14% from a mean baseline concentration of 4662.4 ±1266.17 to 3697.1 ±1547.9 (μg/l) after the study 15 month follow up period (P=0.0006), whereas DFO alone was ineffective. Cardiac function decreased by a percentage of (-4.74 ± 12.89) from 68.64%±6.97% to 60.98%±7.22% in patients on DFO (p= 0.0001) and from 67.39%±6.49% to 63.91%±8.51% in patients receiving combination therapy (p= 0.031). Mean decrease was greater in DFO regimen (-10.53 ± 11.89) than that seen in patients on combination therapy (-4.74 ± 12.89) (p= 0.035). Conclusions This study reveals aspects of the current status of ICT outcomes in Syria. Our results prove high prevalence of iron overload in patients with BTM despite their receiving ICTs free of charge. Patients are not achieving target serum ferritin thresholds despite chronic treatment with DFO for iron overload. This may suggest its poor clinical effectiveness within the real-world, and necessitates active measures to improve patients’ compliance. The underlying causes of these suboptimal therapeutic outcomes of all ICT regimens should be further investigated, and the cost-effectiveness of ICTs should be reconsidered by decision makers. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Iron Chelation Therapy with Deferasirox Results in Improvement of Liver Enzyme Level in Patients with Iron Overload-Associated Liver Dysfunction

2010 ◽  
Vol 2010 ◽  
pp. 1-3 ◽  
Author(s):  
Yasuo Miura ◽  
Yusuke Matsui ◽  
Hitomi Kaneko ◽  
Mitsumasa Watanabe ◽  
Mitsuru Tsudo
Keyword(s):  
Iron Overload ◽  
Liver Dysfunction ◽  
Chelation Therapy ◽  
Enzyme Level ◽  
Elevated Serum ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Similar Efficacy ◽  
Iron Chelation Therapy ◽  
Red Blood Cell Transfusions

Iron chelation therapy (ICT) has been applied for the patients with iron overload-associated liver dysfunction since it is one of the causes of death in patients with intractable hematological diseases requiring multiple red blood cell transfusions. Recently, deferasirox (DSX), a novel, once-daily oral iron chelator, was demonstrated to have similar efficacy to the conventional continuous infusion of deferoxamine on a decrease in serum ferritin (SF) level in heavily transfused patients. We show three cases of transfusion-mediated iron-overloaded patients with an elevated serum alanine aminotransaminase (ALT). All three patients who received the ICT with DSX showed a decrease in ALT level in association with a decrease in SF level. It is suggested that DSX therapy could be considered to expect the improvement of liver damage for iron-overloaded patients with an abnormal ALT level.

scholarly journals Potential Effects of Silymarin and Its Flavonolignan Components in Patients withβ-Thalassemia Major: A Comprehensive Review in 2015

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Hadi Darvishi Khezri ◽  
Ebrahim Salehifar ◽  
Mehrnoush Kosaryan ◽  
Aily Aliasgharian ◽  
Hossein Jalali ◽  
...  
Keyword(s):  
Iron Overload ◽  
Chelation Therapy ◽  
Experimental Studies ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Multiple Organ ◽  
Cochrane Library ◽  
Iron Chelation Therapy ◽  
Globin Chains ◽  
Multiple Blood

Majorβ-thalassemia (β-TM) is one of the most common inherited hemolytic types of anemia which is caused as a result of absent or reduced synthesis ofβ-globin chains of hemoglobin. This defect results in red blood cells lysis and chronic anemia that can be treated by multiple blood transfusions and iron chelation therapy. Without iron chelation therapy, iron overload will cause lots of complications in patients. Antioxidant components play an important role in the treatment of the disease. Silymarin is an antioxidant flavonoid isolated fromSilybum marianumplant. In the present study, we reviewed clinical and experimental studies investigating the use of silymarin prior to September 1, 2015, using PubMed, ISI Web of Knowledge, Science Direct, Scopus, Ovid, and Cochrane Library databases and we evaluated the potential effects of silymarin on controlling the complications induced by iron overload in patients withβ-TM. Based on the results of the present study, we can conclude that silymarin may be useful as an adjuvant for improving multiple organ dysfunctions.

scholarly journals Comparison of Visual Evoked Potential in Thalassemia Patients Receiving Iron Chelation Therapy

2021 ◽  
Vol 8 (12) ◽  
pp. 125-129
Author(s):  
Mridul Yadav ◽  
Shelja Deswal ◽  
Deswal .
Keyword(s):  
Side Effects ◽  
Iron Overload ◽  
Visual Evoked Potential ◽  
Evoked Potential ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Iron Chelation Therapy ◽  
Ocular Toxicity ◽  
Visual Evoked

Patients of thalassemia require iron chelation therapy for the treatment of iron overload in the form of desferrioxamine (DFO), combination of DFO and deferiprone and oral deferiprone only. One of the side effects of DFO is ocular toxicity. Present study was conducted to elicit the subclinical effects of DFO on visual pathways by doing Visual Evoked Potential (VEP). Forty five patients of thalassemia major were divided into three groups (I, II &III) based on their iron chelation therapy as desferrioxamine, combination of desferrioxamine& deferiprone and only deferiprone respectively. VEP was recorded in each group and comparison was done. In VEP P100 was significantly prolonged in the group of thalassemia patients receiving DFO and combination of DFO and deferiprone suggesting vulnerability to ocular toxicity of DFO. We can suggest that in patients receiving chronic DFO therapy, VEPs may be considered to monitor the toxic effects of DFO on visual system. Keywords: Thalassemia, iron chelation, visual evoked potential.

scholarly journals Earlier detection of glomerular dysfunction in β-thalassemia major patients

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Waseem F. Al Tameemi ◽  
Zainab M. J. Altawry
Keyword(s):  
Serum Creatinine ◽  
Iron Overload ◽  
Cystatin C ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Therapeutic Index ◽  
Thalassemia Major ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Thalassemia Major Patient

Chronic transfusions program in β-thalassemia patients will inevitably lead to iron overload with a significant morbidity and mortality. Glomerular filtration rate (GFR) is progressively declined in relation to iron overload as well as chronic anemia. Objective is to define levels of Cystatin C in transfusion dependent β-thalassemia major patients as a sensitive marker for detection of earlier glomerular dysfunction in addition to understand the effect of iron overload, chelating therapy and hepatitis infection. A cross sectional study conducted at Al-Basrah Hemoglobinopathy Centre for the period from September 2017 to January 2018 to enroll 75 β-thalassemia major patients. Data collected included duration of the disease, total transfusion requirement, details of chelation therapy and its therapeutic index. In addition to blood urea, serum creatinine and Cystatin C with estimated GFR (eGFR). The mean Cystatin C was 1.075 mg/L where 66.6% of patients had abnormal renal function which is higher proportion than those with renal (42.6%) detected according to serum creatinine level Cystatin C was significantly higher in patients who received desferrioxamine as compared to those received deferasirox (P=0.007), in accordance with GFR which is significantly higher in patients receiving the latter chelation therapy (P=0.009). A significant inverse relationship between Cystatin C, and GFR, while positive relationship between ferritin and Cystatin C (P=0.0001, 0.001 respectively). Cyctatin C is better for detection and monitoring of glomerular dysfunction in B thalassemia major patient which is already not uncommon complications for the disease and iron chelation therapy.

scholarly journals Systemic Heme and Iron Overload Results in Depletion of Serum Hemopexin, Haptoglobin and Transferrin and Correlates with Markers of Endothelial Activation and Lipid Oxidation in Beta Thalassemia Major and Intermedia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2469-2469
Author(s):  
Francesca Vinchi ◽  
Gregory M Vercellotti ◽  
John D. Belcher ◽  
Eitan Fibach ◽  
Hala Zreid ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Iron Overload ◽  
Research Funding ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Endothelial Activation ◽  
Beta Thalassemia ◽  
Iron Chelation Therapy ◽  
Cell Disease

Abstract Beta thalassemia is an inherited hemoglobinopathy due to reduced synthesis of Beta globin chains and, consequently, of hemoglobin A (a2b2). The clinical manifestations are mainly the result of chronic anemia and iron overload. The latter is due to increased iron absorption, induced by accelerated but ineffective erythropoiesis, and recurrent red blood cell transfusions. Alfa-chains and iron excess promote oxidative damage of red blood cell membrane, resulting in macrophage sequestration and extravascular hemolysis, and to a lower extent, in intravascular hemolysis, with consequent release of hemoglobin (Hb), heme and iron. Increasing evidence suggests that free heme exerts vasculotoxic, pro-inflammatory and procoagulant effects due to its ability to trigger endothelial and immune cells activation. In addition, a role for heme and iron has been postulated in the pathogenesis of other vascular diseases, including atherosclerosis. In mouse models of Beta thalassemia and sickle cell disease, circulating heme levels are elevated and correlate with the exhaustion of systemic scavengers for hemoglobin and heme, haptoglobin and hemopexin, respectively, as well as with severe endothelial dysfunction and inflammation. Hemopexin-based therapies significantly improve endothelial damage, vascular oxidative stress and inflammation in these mice (Vinchi et al., Circulation 2013, Blood 2016; Vercellotti GM. et al., Mol Med 2016). Whereas more data are reported on sickle patients in this regard, few data are available in patients with Beta thalassemia. In the present study, we examined serum samples from a cohort of 60 patients with Beta thalassemia major (age 11.5 ± 6.8, 44% males-56% females, Hb 7.69 ± 1.22 mg/dl, transfused every 3-4 weeks) and 7 patients with Beta thalassemia intermedia (age 14 ± 12 , 70% males-30% females, Hb 8.4 ± 0.74 mg/dl, transfused every 4-5 weeks). 10% of the patients received inconsistent iron chelation therapy. Serum from 10 healthy subjects (age 22.7±15.3, 50% males-50% females, Hb 13.12±1.15 mg/dl) served as control. Both groups of patients show high systemic heme and iron levels, which associate with a severe drop in serum haptoglobin, hemopexin and transferrin. Consistently, transferrin saturation (12.4±2 vs 79.6±24 %) and serum ferritin (55.14 ±0.23 vs 4919.2 ±2657.4 ng/ml) are elevated. Interestingly, these patients present with high systemic levels of the soluble adhesion molecules sVCAM-1 and sICAM-1, markers of enhanced endothelial activation. In addition, they show increased levels of serum malondialdehyde, a well-known marker of lipid peroxidation and oxidative stress, and high levels of circulating oxidized low density lipoproteins (oxLDL). All parameters significantly correlate with increased systemic heme and iron indices as well as decreased haptoglobin, hemopexin and transferrin levels. In conclusion, Beta thalassemia patients show a strong correlation between systemic heme and iron overload, depletion of the respective scavengers, and markers of oxidative stress and endothelial dysfunction, thus confirming studies in animal models. These results emphasize the involvement of serum hemoglobin, heme and iron in the pathophysiology of Beta thalassemia, including vascular dysfunction, and the key protective role of their carriers. These findings are relevant for disorders hallmarked by vasculopathy, such as sickle cell disease and Beta thalassemia, as well as cardiovascular diseases, such as atherosclerosis. Our data support the potential therapeutic benefit of the administration of hemoglobin/heme scavengers along with efficient iron chelation therapy to counteract heme- and iron-driven toxicity. (The last three authors equally contributed to the work) ****P<0.0001 Disclosures Vercellotti: CSL-Behring: Research Funding; Imara: Research Funding. Belcher:Cydan/Imara: Research Funding; CSL-Behring: Research Funding.

Iron Chelation Therapy in CAPD: A New and Effective Treatment of Iron Overload Disease in Esrd Patients

1983 ◽  
Vol 3 (2) ◽  
pp. 99-101 ◽  
Author(s):  
Glen H Stanbaugh ◽  
A. W, Holmes Diane Gillit ◽  
George W. Reichel ◽  
Mark Stranz
Keyword(s):  
Peritoneal Dialysis ◽  
Iron Overload ◽  
End Stage Renal Disease ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Iron Chelation Therapy ◽  
Peritoneal Dialysate ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

A patient with end-stage renal disease on CAPD, and with massive iron overload is reported. This patient had evidence of myocardial and hepatic damage probably as a result of iron overload. Treatment with desferoxamine resulted in removal of iron in the peritoneal dialysate. On the basis of preliminary studies in this patient it would appear that removal of iron by peritoneal dialysis in conjunction with chelation therapy is safe and effective. This finding should have wide-ranging signficance for patients with ESRD.

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