scholarly journals Efficacy and safety of combined oral iron chelation therapy with deferasirox and deferiprone in a patient with beta-thalassemia major and persistent iron overload

2014 ◽  
Vol 49 (1) ◽  
pp. 72 ◽  
Author(s):  
Samin Alavi ◽  
Elham Sadeghi ◽  
Azin Ashenagar
Keyword(s):  
Iron Overload ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Oral Iron ◽  
Beta Thalassemia ◽  
Iron Chelation Therapy ◽  
Efficacy And Safety ◽  
Beta Thalassemia Major

scholarly journals Covid-19 Infection in a Case of Transfusion Dependent Beta Thalassemia Major - A Case Report and Review of Literature

2021 ◽  
Vol 10 (18) ◽  
pp. 1365-1368
Author(s):  
Anamika Giri ◽  
Sameera Dronamraju ◽  
Sourya Acharya ◽  
Samarth Shukla ◽  
Sunil Kumar
Keyword(s):  
Chelation Therapy ◽  
Indian Subcontinent ◽  
Killer Cell ◽  
Iron Chelation ◽  
Suppressor Cells ◽  
Thalassemia Major ◽  
Sub Saharan Africa ◽  
Beta Thalassemia ◽  
Iron Chelation Therapy ◽  
Beta Thalassemia Major

Thalassemia, derived from Thalassa [Greek: Sea] refers to a cluster of hereditary haemoglobinopathies initially reported in areas of Sub-Saharan Africa, the Indian subcontinent, Southeast Asia, and the Mediterranean where malaria was (or is) endemic. Currently, it is the most frequently recognized haemoglobinopathy, and has been correlated with a plethora of immune system changes such as neutropenia, natural killer cell dysfunctions, increased activity of CD8 suppressor cells, along with disturbances in macrophage function, chemotaxis, phagocytosis, and interferons INFγ production.1 The reduction in the alpha or beta chain that leads to the production of haemoglobin is the key pathophysiology behind thalassemia. Therefore, weakened red blood cells can contribute to inadequate erythropoiesis and haemolytic anaemia. Thalassemia diseases are known as transfusion-dependent or non-dependent according to either their beta-globin chain genotype or their clinical path. The most serious type of thalassemia is beta-thalassemia major, and it is transfusiondependent, presenting in early infancy.2 A diagnosis of β-thalassemia major (BTM) means lifelong, regular transfusions, supplemented with adequate iron chelation therapy for the patient.3 This also means that unless adequate blood screening and hygiene procedures are in place, patients with BTM are at a risk of transfusion transmitted infections (TTI).4 Many countries have been prompted by the spread of Covid-19 infection to shutter routine outpatient coronary health care units before the pandemic is over, which also extends to people with thalassemia, who require regular follow-ups. While Covid-19 infection rates remain high, patients with thalassemia with planned cardiovascular examinations are advised to delay their medical appointments for a minimum of 3 months.1 In addition, according to the statement published by the Thalassemia International Foundation on the 13th of July, 2020, patients with hemoglobinopathies are at a greater risk in acquiring the Covid-19 infection, posing an additional challenge to the patients, families, and medical staff managing these disorders.5 Thalassaemic patients have reduced levels of protein S and protein C; elevated aggregation of platelets; and recruitment of monocytes, granulocytes, and endothelial cells. Patients of thalassemia also show elevated markers of platelet and coagulation activation, even in the absence of major thromboembolic events. An increase in D-Dimer levels is also seen in most Covid-19 patients who are hospitalised, attributable to the underlying inflammatory process.1 A variety of questions have been raised during the ongoing Covid-19 pandemic with respect to diagnostic and clinical approaches towards this particular population. The precise path of infection with Covid-19 in those patients has yet to be elucidated.2 The progression of Covid-19 infection in patients with hemoglobinopathy in general and thalassemia in particular is not fully known and is still an area of discussion and under review. We report a case of a 30-year-old male patient, a known case of beta thalassemia major on maintenance transfusion and iron chelation therapy who acquired Covid-19 infection.

Renal Dysfunction in Patients with Beta-Thalassemia Major Receiving Iron Chelation Therapy either with Deferoxamine and Deferiprone or with Deferasirox

2010 ◽  
Vol 123 (3) ◽  
pp. 148-152 ◽  
Author(s):  
Marina Economou ◽  
Nikoletta Printza ◽  
Aikaterini Teli ◽  
Vassiliki Tzimouli ◽  
Ioanna Tsatra ◽  
...  
Keyword(s):  
Renal Dysfunction ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Iron Chelation Therapy ◽  
Beta Thalassemia Major

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.

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.

Effective and Safe Deferasirox Treatment of Patients with Various anemia's and Transfusional Iron-Overload in the Medical Practice: Results From Two German Observational Studies

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5165-5165
Author(s):  
Christian Junghanss ◽  
Rudolf Schlag ◽  
Bernd Gaede ◽  
Matthias Moelle ◽  
Steffen Doerfel ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Observational Studies ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Beta Thalassemia ◽  
Final Visit ◽  
Iron Chelation Therapy ◽  
The Mean

Abstract Abstract 5165 Background: Progressive anaemia is highly prevalent amongst many malignant diseases leading to RBC transfusion-dependency. Therefore transfusion-related iron overload (IOL) is common in these patients (pts) and can result in multiple organ failure. Iron chelation therapy prevents organ failure, reduces the risk of infections and can improve hematopoesis in some diseases. The once-daily oral iron chelator deferasirox has been shown to reduce iron overload in pts with various transfusion-dependent anaemias assessed by serum ferritin (SF). Despite extensive knowledge of iron chelation in MDS or beta-thalassemia pts, data in pts with other anaemias is limited. Here, we present data from a subgroup of transfusion-related IOL pts that were included two non-interventional studies (EXTEND, EXJANGE) performed in Germany and who suffered from diseases other than MDS or beta thalassemia. Methods: 130 pts with various malignant diseases such as myeloproliferative disorders (43 pts, including 31 pts particular specified as myelofibrosis), acute myeloid leukaemia (14 pts), sickle cell anaemia (6 pts), aplastic anaemia (11), congenital aplastic anaemia (5) or Non-Hodgkin's lymphoma (6 pts) were treated with deferasirox in the daily-routine setting of office-based physicians and included in either the EXTEND or EXJANGE study. Patient with MDS or beta-thalassemia were also included in the studies, but are excluded from this analysis. Analysis is based on 1-year pooled data of these two, multicenter, non-interventional observational studies. Transfusion-dependent pts with IOL with or without prior chelation were enrolled and received the iron chelator deferasirox. Prescription of deferasirox, just as inclusion and exclusion criteria was in accordance with the terms of Exjade marketing authorization in the EU. Efficacy and safety parameters, including serum ferritin and adverse events (AEs), were collected in 2-monthly intervals. Results: 98 pts had no prior chelation therapy (51 M, 45 F, 2 missing; mean age 63.3, range 3.2–91.9 yrs) and a median baseline SF of 2,968 (range 561–11, 423) ng/mL. 32 pts had prior received prior chelation therapy (mainly with desferal; 17 M, 15 F; mean age 50.1, range 3.5–80.9 yrs) and a median baseline SF of 2,635 (range 539–19, 540) ng/mL. The mean number of prior red blood cell transfusions was 55. The mean prescribed daily dose of deferasirox at the first visit was 16.3 mg/kg/d rising up to 18.1 mg/kg/d after 12 months. During treatment, median SF levels clearly decreased from first to final visit [-806 ng/mL; p<0.0001 (explorative analysis)] in the chelation-naïve and also in the pre-chelated population [-300 ng/ml; p = 0.1705 (explorative analysis)]. The median observation period and days on therapy was 349 and 343 days, respectively. At final visit 74 pts (56.9%) were still on deferasirox therapy. Reasons for discontinuation by the final visit included 19 AEs (35.2%). 45 pts (34.6%) experienced an investigator assessed drug-related AE. The most common drug-related AEs were diarrhea (n=17; 37.8%), nausea (n=11; 24.4%) and blood creatinine increased (n=6; 13.3%). As in previous clinical trials, serum creatinine clearances showed a minor decrease over the study period (median decrease until final visit: 4 ml/min). Conclusion: Our analysis confirmed that deferasirox is effective and well tolerated in chelation-naïve as well as in previously chelated pts with transfusion-related IOL and diseases other than MDS or beta thalassemia. As baseline serum ferritin values were >2,500 ng/mL even in pts with prior chelation therapy, adequate chelation treatment should be considered earlier at a serum ferritin >1,000 ng/mL in pts with transfusion-dependent IOL for adequate iron chelation therapy. Disclosures: Junghanss: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Haus:Novartis Pharma: Employment. Junkes:Novartis: Employment. Leismann:Novartis: Employment.

Supportive care and chelation therapy in MDS: are we saving lives or just lowering iron?

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 664-672 ◽  
Author(s):  
Heather A. Leitch ◽  
Linda M. Vickars
Keyword(s):  
Iron Overload ◽  
Supportive Care ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Beta Thalassemia ◽  
Ventricular Ejection Fraction ◽  
The Impact

AbstractThe myelodysplastic syndromes (MDS) are characterized by cytopenias and risk of transformation to acute myeloid leukemia (AML). Although new treatments are available, a mainstay in MDS remains supportive care, which aims to minimize the impact of cytopenias and transfusion of blood products. Red blood cell (RBC) transfusions place patients at risk of iron overload (IOL). In beta-thalassemia major (BTM), IOL from chronic RBC transfusions inevitably leads to organ dysfunction and death. With iron chelation therapy (ICT), survival in BTM improved from the second decade to near normal and correlated with ICT compliance. Effects of ICT in BTM include reversal of cardiac arrhythmias, improvement in left ventricular ejection fraction, arrest of hepatic fibrosis, and reduction of glucose intolerance.It is not clear whether these specific outcomes are applicable to MDS. Although retrospective, recent studies in MDS suggest an adverse effect of transfusion dependence and IOL on survival and AML transformation, and that lowering iron minimizes this impact. These data raise important points that warrant further study. ICT is potentially toxic and cumbersome, is costly, and in MDS patients should be initiated only after weighing potential risks against benefits until further data are available to better justify its use. Since most MDS patients eventually require RBC transfusions, the public health implications both of transfusion dependence and ICT in MDS are considerable. This paper summarizes the impact of cytopenias in MDS and treatment approaches to minimize their impact, with a focus on RBC transfusions and their complications, particularly with respect to iron overload.

Assessment of the Relationship Between Iron Overload Based on Cardiac T2* MRI and Fragmented QRS in Beta-Thalassemia Major Patients

2020 ◽  
Vol 21 (8) ◽  
Author(s):  
Yazdan Ghandi ◽  
Danial Habibi ◽  
Aziz Eghbali
Keyword(s):  
Iron Overload ◽  
Chelation Therapy ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Cardiac Iron ◽  
Fragmented Qrs ◽  
Beta Thalassemia Major ◽  
Cardiac Iron Overload ◽  
The Mean ◽  
T2 Mri

Background: Cardiac involvement in beta-thalassemia major patients is an important cause of mortality. Therefore, in these patients, timely diagnosis of cardiac disorder is essential. Objectives: The present study aimed at determining the association between cardiac iron overload and fragmented QRS (fQRS). Methods: This cross-sectional study was conducted on 40 β-TM patients, aged 5 - 40 years. The presence of fQRS was evaluated in 12-lead surface electrocardiograms. Cardiac T2* MRI was performed to determine the iron overload. The patients were divided into four groups of chelation therapy. Results: The mean age of patients was reported to be 22.50 ± 6.75 years. The groups showed no significant difference regarding gender, age, or left ventricular ejection fraction. The presence of fQRS was detected in 10 patients (25%), while T2* value was lower than 20 ms in 10 patients (25%). The mean age of patients with and without fQRS was 26.23 ± 2.71 and 19.40 ± 2.61 years, respectively (P = 0.001). The univariate analysis indicated that fQRS had a significant relationship with cardiac iron overload (OR = 5; 95% CI: 1.04 - 23.99; P < 0.044). The multiple logistic regression analysis represented a significant association between iron overload and fQRS (OR = 5.556; 95% CI: 1.027 - 30.049). The sensitivity and specificity of the fQRS against MRI were equal to 50% and 83.3% respectively. Conclusions: The absence of fQRS on ECGs could be a good predictor of the lack of cardiac iron overload in β-TM patients. The results showed that fQRS might indicate the no need for close monitoring for cardiac overload with cardiac MRI and aggressive chelation therapy.

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