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 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.

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.

scholarly journals 329 Heart failure predictive value of the electric risk score in patients suffering from thalassemia major

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Elisa Tomarelli ◽  
Federica Moscucci ◽  
Anna Annunziata Losardo ◽  
Pellegrina Pugliese ◽  
Mauro Schina ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Score ◽  
Ventricular Hypertrophy ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Myocardial Damage ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
P Value ◽  
Iron Chelation Therapy

Abstract Aims Complications associated with iron accumulation were highly recurrent in thalassemia patients, who underwent frequent blood transfusions, in particular hemosiderotic cardiomyopathy which could lead to heart failure and arrhythmias. Nowadays, the better iron chelation therapy has improved cardiovascular morbidity in these patients; nevertheless, mild impairment should be seek for and eventually treated. The objective of our study was to evaluate the possibility of using early electrocardiographic markers of myocardial damage and predictors of mortality, such as the Electric Risk Score (ERS). Methods and results 73 patients with thalassemia major were enrolled in this study, which were divided into two groups, with 45 years old as cut off. Anamnestic, clinical, electrocardiographic, and echocardiographic data were collected. From ECG, ERS was obtained. over 45 yrs-old group of pts, in addition to a predictable increase in the prevalence of traditional cardiovascular risk factors and drug intake, an alteration of the QRS-T angle (14[30] vs. −4[28], p value: &lt;0.0001) and an increased prevalence of left ventricular hypertrophy (2.88 ± 0.86 vs. 2.40 ± 0.57 p value: &lt;0.05) were found. In patients taking drugs with possible interactions with the ventricular repolarization phase, there is a slight increase in the QT interval, left ventricular hypertrophy and a reduction in Tpeak-Tend (Table 1). Electrocardiographic values in groups of patients with different age groups who are taking therapies that can affect QT. The echocardiogram revealed an increase in the end-diastolic diameter of the right ventricle (26 ± 3 vs. 28 ± 3 mm, P-value: 0.05) in the group of patients over the age of 45, a decrease in the acceleration time of the pulmonary systolic flow (138 ± 25 vs. 125 ± 13 ms, P-value: 0.04) and TAPSE (25 ± 3 vs. 22 ± 4 mm, P-value: 0.002). Conclusions From the data in our study it emerged that an appropriate iron-chelation therapy is able to effectively counteract the hemosiderotic cardiomyopathy of thalassemic patients so as to detect electro- and echocardiographic anomalies only in patients of more advanced age, a result that we think both the consequence, not so much of iron overload, but of an increase in the prevalence of age- and gender-related cardiovascular risk factors. The initial changes in cardiac electromechanics, which can be assessed with the aforementioned methods, we believe, can become a very early sign of specific myocardial damage. 329 Figure 1Electrical risk score parameters.

scholarly journals Testicular function in patients with regular blood transfusion for thalassemia major

2015 ◽  
Vol 9 (2) ◽  
Author(s):  
Sukumarn Siripunthana ◽  
Taninee Sahakitrungruang ◽  
Suttipong Wacharasindhu ◽  
Darintr Sosothikul ◽  
Vichit Supornsilchai
Keyword(s):  
Blood Transfusion ◽  
Chelation Therapy ◽  
Cell Function ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Delayed Puberty ◽  
Control Group ◽  
Blood Transfusions ◽  
Testicular Function ◽  
Iron Chelation Therapy

AbstractBackgroundRegular blood transfusion and iron chelation therapy have improved the quality of life of patients with thalassemia and increased their longevity, but transfusion also increases the frequency of endocrine complications, possibly because of iron deposition in the pituitary gland or the gonads, or both.ObjectiveTo evaluate testicular function in patients with thalassemia major by basal hormonal study, and identify risk factors for dysfunction.MethodsWe performed a cross-sectional study of 28 patients with thalassemia major aged 11.7 ± 1.8 (8–14.9) years (15 in prepuberty, 13 in puberty with no delayed puberty) who had regular blood transfusions. A normal control group comprised 64 boys who were matched for age and Tanner genital stage.ResultsThe mean level of serum ferritin in the previous year was 1,575 ± 642 ng/mL, and the onset of blood transfusion was at 3.8 ± 2.3 years and iron chelation therapy was 6.6 ± 2.8 years. The trend for anti-Müllerian hormone levels in patients and controls was similar with age, and although higher in the patients, particularly at Tanner stage II, was not significantly different. Testosterone levels were lower in the patients compared with controls; particularly at Tanner stages IV–V (290.88 vs. 537.4 ng/dL,ConclusionPatients who received regular blood transfusions had normal Sertoli cell function. Leydig cell dysfunction may occur, even though the patients had a normal pubertal onset.

Long-Term Safety and Effectiveness of Iron-Chelation Therapy with Deferiprone for Thalassemia Major

1998 ◽  
Vol 339 (7) ◽  
pp. 417-423 ◽  
Author(s):  
Nancy F. Olivieri ◽  
Gary M. Brittenham ◽  
Christine E. McLaren ◽  
Douglas M. Templeton ◽  
Ross G. Cameron ◽  
...  
Keyword(s):  
Chelation Therapy ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Iron Chelation Therapy
Sign in / Sign up

Export Citation Format

Share Document