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1.
Ann Hematol ; 103(6): 1887-1896, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38581547

RESUMO

We evaluated the impact of the genotype on clinical and hematochemical features, hepatic and cardiac iron levels, and endocrine, hepatic, and cardiovascular complications in non-transfusion-dependent (NTD) ß-thalassemia intermedia (TI) patients. Sixty patients (39.09 ± 11.11 years, 29 females) consecutively enrolled in the Myocardial Iron Overload in Thalassemia project underwent Magnetic Resonance Imaging to quantify iron overload, biventricular function parameters, and atrial areas and to detect replacement myocardial fibrosis. Three groups of patients were identified: homozygous ß+ (N = 18), heterozygous ß0ß+ (N = 22), and homozygous ß0 (N = 20). The groups were homogeneous for sex, age, splenectomy, hematochemical parameters, chelation therapy, and iron levels. The homozygous ß° genotype was associated with significantly higher biventricular end-diastolic and end-systolic volume indexes and bi-atrial area indexes. No difference was detected in biventricular ejection fractions or myocardial fibrosis. Extramedullary hematopoiesis and leg ulcers were significantly more frequent in the homozygous ß° group compared to the homozygous ß+ group. No association was detected between genotype and liver cirrhosis, hypogonadism, hypothyroidism, osteoporosis, heart failure, arrhythmias, and pulmonary hypertension. Heart remodelling related to a high cardiac output state cardiomyopathy, extramedullary hematopoiesis, and leg ulcers were more pronounced in patients with the homozygous ß° genotype compared to the other genotypes analyzed. The knowledge of the genotype can assist in the clinical management of NTD ß-TI patients.


Assuntos
Genótipo , Sobrecarga de Ferro , Ferro , Talassemia beta , Humanos , Talassemia beta/genética , Talassemia beta/complicações , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Sobrecarga de Ferro/genética , Sobrecarga de Ferro/etiologia , Ferro/metabolismo , Úlcera da Perna/etiologia , Úlcera da Perna/genética , Hematopoese Extramedular/genética , Imageamento por Ressonância Magnética , Miocárdio/patologia , Miocárdio/metabolismo , Cirrose Hepática/genética , Cirrose Hepática/complicações , Homozigoto
2.
Ann Med ; 56(1): 2338246, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38604224

RESUMO

BACKGROUND: Thalassemia is the most prevalent hereditary anaemia worldwide. Severe forms of thalassemia can lead to reduced life expectancy due to disease-related complications. OBJECTIVES: To investigate the survival of thalassemia patients across varying disease severity, causes of death and related clinical factors. PATIENTS AND METHODS: We conducted a retrospective review of thalassemia patients who received medical care at Chiang Mai University Hospital. The analysis focused on survival outcomes, and potential associations between clinical factors and patient survival. RESULTS: A total of 789 patients were included in our study cohort. Among them, 38.1% had Hb H disease, 35.4% had Hb E/beta-thalassemia and 26.5% had beta-thalassemia major. Half of the patients (50.1%) required regular transfusions. Sixty-five patients (8.2%) had deceased. The predominant causes of mortality were infection-related (36.9%) and cardiac complications (27.7%). Transfusion-dependent thalassemia (TDT) (adjusted HR 3.68, 95% CI 1.39-9.72, p = 0.008) and a mean serum ferritin level ≥3000 ng/mL (adjusted HR 4.18, 95% CI 2.20-7.92, p < 0.001) were independently associated with poorer survival. CONCLUSIONS: Our study highlights the primary contributors to mortality in patients with thalassemia as infection-related issues and cardiac complications. It also underscores the significant impact of TDT and elevated serum ferritin levels on the survival of thalassemia patients.


Assuntos
Cardiopatias , Sobrecarga de Ferro , Talassemia , Talassemia beta , Humanos , Talassemia beta/complicações , Talassemia beta/epidemiologia , Talassemia beta/terapia , Tailândia/epidemiologia , Causas de Morte , Talassemia/complicações , Fatores de Risco , Sobrecarga de Ferro/etiologia
3.
Rev Med Interne ; 45(4): 187-193, 2024 Apr.
Artigo em Francês | MEDLINE | ID: mdl-38519305

RESUMO

INTRODUCTION: The life expectancy of ß-thalassemia patients has increased over the last 20 years. In this study, we evaluated the current health status and quality of life of these patients managed in a reference center in Marseille. METHODS: This is a single-center, descriptive study conducted between June and August 2019 in patients over 18 years of age with ß-thalassemia major or intermedia. Clinical and paraclinical data were collected retrospectively and the SF-36 health survey questionnaire was proposed to each patient. RESULTS: 43 of 64 selected patients were included and divided into 2 groups: 35 patients with transfusion-dependent ß-thalassemia and 8 patients with non-transfusion-dependent ß-thalassemia. Liver iron overload is the most frequent complication, present in 80% of transfusion-dependent and 62.5% of non-transfusion-dependent patients. Cardiac iron overload is present only in the transfusion dependent ß-thalassemia group (20%). Hypogonadotropic hypogonadism remains the most common endocrine disorder (41.9%) followed by osteoporosis (37.2%). Among the 31 patients who completed the SF-36 questionnaire, physical and mental quality of life scores were lowered in transfusion dependent (respectively 42.7 and 46.8) as in non-transfusion-dependent patients (respectively 43.8 and 28.9). CONCLUSION: Despite an improvement in medical care, our patients with ß-thalassemia show an alteration in their quality of life that will need to be characterized in the entire French cohort.


Assuntos
Nível de Saúde , Qualidade de Vida , Talassemia beta , Humanos , Talassemia beta/terapia , Talassemia beta/epidemiologia , Talassemia beta/complicações , Talassemia beta/psicologia , França/epidemiologia , Masculino , Feminino , Adulto , Estudos Retrospectivos , Adulto Jovem , Pessoa de Meia-Idade , Transfusão de Sangue/estatística & dados numéricos , Sobrecarga de Ferro/epidemiologia , Sobrecarga de Ferro/etiologia , Inquéritos e Questionários , Adolescente
4.
Ann Hematol ; 103(5): 1525-1539, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38519604

RESUMO

INTRODUCTION: The increase in the number of patients with hemoglobinopathies in Europe in recent decades highlights the need for more detailed epidemiological information in Spain. To fulfil this need, the Spanish Society of Pediatric Hematology and Oncology (SEHOP) sponsored the creation of a national registry of hemoglobinopathies known as REHem-AR (Spanish Registry of Hemoglobinopathies and Rare Anemias). Data from the transfusion-dependent (TDT) and non-transfusion-dependent (NTDT) ß-thalassemia cohorts are described and analyzed. METHODS: We performed an observational, multicenter, and ambispective study, which included patients of any age with TDT and NTDT, registered up to December 31, 2021. RESULTS: Among the 1741 patients included, 168 cases of thalassemia were identified (103 TDT and 65 NTDT-patients). Survival at 18 years was 93% for TDT and 100% for NTDT. Regarding management, 80 patients with TDT (77.7%) and 23 patients with NTDT (35.4%) started chelation treatment during follow-up, with deferasirox being the most widely used. A total of 76 patients within the TDT cohort presented at least 1 complication (73.8%), the most frequent being hemosiderosis and osteopenia-osteoporosis. Comparison of both cohorts revealed significant differences in the diagnosis of hepatic hemosiderosis (p = 0.00024), although these were not observed in the case of cardiac iron overload (p = 0.27). DISCUSSION: Our registry enabled us to describe the management of ß thalassemia in Spain and to analyze the morbidity and mortality of the cohorts of patients with TDT and NTDT. Complications related to iron overload in TDT and NTDT account for most of the morbidity and mortality of the disease, which is associated with a considerable social, psychological, and economic impact, although cardiac, osteopathy and endocrinological complications requiring more attention. The convenience and simplicity of online registries make it possible to homogenize variables and periodically update data, thus providing valuable information on these diseases.


Assuntos
Hemossiderose , Sobrecarga de Ferro , Talassemia beta , Criança , Humanos , Talassemia beta/complicações , Talassemia beta/epidemiologia , Talassemia beta/terapia , Transfusão de Sangue , Sobrecarga de Ferro/etiologia , Demografia
5.
Am J Hematol ; 99(6): 1031-1039, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38429922

RESUMO

Patients with sickle cell disease (SCD) and other anemias who receive blood transfusions are at risk of organ damage due to transfusional iron overload. Deferiprone is an iron chelator with a well-established safety and efficacy profile that is indicated for the treatment of transfusional iron overload. Here, we report safety data from the large-scale, retrospective Ferriprox® Total Care Registry, which involved all patients with SCD taking deferiprone following the 2011 approval of deferiprone in the United States through August 2020. A total of 634 patients who had initiated deferiprone treatment were included. The mean (SD) duration of deferiprone exposure in the registry was 1.6 (1.6) years (range 0 to 9.7 years). In the overall patient population (N = 634), 64.7% (n = 410) of patients reported a total of 1885 adverse events (AEs). In subgroup analyses, 54.6% (n = 71) of pediatric patients and 67.3% (n = 339) of adult patients reported AEs. The most common AEs reported in patients receiving deferiprone were sickle cell crisis (22.7%), nausea (12.1%), vomiting (8.7%), abdominal discomfort (5.4%), and fatigue (5.4%). Neutropenia was reported in four (0.6%) patients and severe neutropenia/agranulocytosis (defined as absolute neutrophil count <0.5 × 109/L) was reported in two (0.3%) patients. Of patients with evaluable data, all cases of neutropenia and severe neutropenia/agranulocytosis resolved with deferiprone discontinuation. Results from the nearly 10 years of real-world data collected in the Ferriprox® Total Care Registry demonstrate that deferiprone is safe and well tolerated in patients with SCD or other anemias who have transfusional iron overload.


Assuntos
Anemia Falciforme , Deferiprona , Quelantes de Ferro , Sistema de Registros , Humanos , Deferiprona/uso terapêutico , Deferiprona/efeitos adversos , Anemia Falciforme/tratamento farmacológico , Masculino , Criança , Adulto , Feminino , Adolescente , Quelantes de Ferro/uso terapêutico , Quelantes de Ferro/efeitos adversos , Quelantes de Ferro/administração & dosagem , Estudos Retrospectivos , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Pré-Escolar , Adulto Jovem , Pessoa de Meia-Idade , Lactente
6.
Pediatr Blood Cancer ; 71(5): e30923, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38385860

RESUMO

BACKGROUND: In pediatric transfusion-dependent thalassemia (TDT) patients, we evaluated the prevalence, pattern, and clinical associations of pancreatic siderosis and the changes in pancreatic iron levels and their association with baseline and changes in total body iron balance. PROCEDURE: We considered 86 pediatric TDT patients consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Iron overload (IO) was quantified by R2* magnetic resonance imaging (MRI). RESULTS: Sixty-three (73%) patients had pancreatic IO (R2* > 38 Hz). Global pancreas R2* values were significantly correlated with mean serum ferritin levels, MRI liver iron concentration (LIC) values, and global heart R2* values. Global pancreas R2* values were significantly higher in patients with altered versus normal glucose metabolism. Thirty-one patients also performed the follow-up MRI at 18 ± 3 months. Higher pancreatic R2* values were detected at the follow-up, but the difference versus the baseline MRI was not significant. The 20% of patients with baseline pancreatic IO showed no pancreatic IO at the follow-up. The 46% of patients without baseline pancreatic IO developed pancreatic siderosis. The changes in global pancreas R2* between the two MRIs were not correlated with baseline serum ferritin levels, baseline, final, and changes in MRI LIC values, or baseline pancreatic iron levels. CONCLUSIONS: In children with TDT, pancreatic siderosis is a frequent finding associated with hepatic siderosis and represents a risk factor for myocardial siderosis and alterations of glucose metabolism. Iron removal from the pancreas is exceptionally challenging and independent from hepatic iron status.


Assuntos
Sobrecarga de Ferro , Siderose , Talassemia , Talassemia beta , Humanos , Criança , Ferro , Talassemia beta/complicações , Talassemia beta/diagnóstico por imagem , Talassemia beta/terapia , Siderose/complicações , Siderose/metabolismo , Siderose/patologia , Sobrecarga de Ferro/diagnóstico por imagem , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/metabolismo , Pâncreas/diagnóstico por imagem , Pâncreas/metabolismo , Pâncreas/patologia , Talassemia/complicações , Fígado/diagnóstico por imagem , Fígado/patologia , Imageamento por Ressonância Magnética/métodos , Ferritinas , Glucose/metabolismo
7.
Hemoglobin ; 48(1): 47-55, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38369714

RESUMO

The study aimed to determine efficacy and safety of generic deferasirox monotherapy. Deferasirox was administered in transfusion-induced iron overloaded thalassemia. Efficacy was defined as responders and nonresponders by ≤ 15 reduced serum ferritin from baseline. Adverse events were also monitored. Fifty-two patients with mainly Hb E/ß-thalassemia at the mean (SD) age of 8.7 (4.1) years, were enrolled. The mean (SD) daily transfusion iron load was 0.47 (0.1) mg/kg and maximum daily deferasirox was 35.0 (6.2) mg/kg. Altogether, 52, 40 and 18 patients completed the first, second and third years of study, respectively. The median baseline serum ferritin 2,383 ng/mL decreased to 1,478, 1,038 and 1,268 ng/mL at the end of first, second and third years, respectively, with overall response rate at 73.1% (38/52). Patients with baseline serum ferritin >2,500 ng/mL showed a change in serum ferritin higher than those ≤2,500 ng/mL starting from the 9th month of chelation. Adverse events were found in 5 of 52 patients (9.6%) including transaminitis (n = 2), one each of proteinuria, rash and proximal tubular dysfunction which resolved after transient stopping or decreasing the chelation dose. Generic deferasirox was effective and safe among pediatric patients with transfusion-induced iron overloaded thalassemia.


Assuntos
Sobrecarga de Ferro , Talassemia , Humanos , Criança , Deferasirox/efeitos adversos , Quelantes de Ferro/efeitos adversos , Benzoatos/efeitos adversos , Triazóis/efeitos adversos , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Talassemia/tratamento farmacológico , Ferro , Ferritinas
8.
BMJ Open ; 14(2): e077342, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331857

RESUMO

INTRODUCTION: Despite the improvement in medical management, many patients with transfusion-dependent ß-thalassaemia die prematurely due to transfusion-related iron overload. As per the current guidelines, the optimal chelation of iron cannot be achieved in many patients, even with two iron chelators at their maximum therapeutic doses. Here, we evaluate the efficacy and safety of triple combination treatment with deferoxamine, deferasirox and deferiprone over dual combination of deferoxamine and deferasirox on iron chelation in patients with transfusion-dependent ß-thalassaemia with very high iron overload. METHODS AND ANALYSIS: This is a single-centre, open-label, randomised, controlled clinical trial conducted at the Adult and Adolescent Thalassaemia Centre of Colombo North Teaching Hospital, Ragama, Sri Lanka. Patients with haematologically and genetically confirmed transfusion-dependent ß-thalassaemia are enrolled and randomised into intervention or control groups. The intervention arm will receive a combination of oral deferasirox, oral deferiprone and subcutaneous deferoxamine for 6 months. The control arm will receive the combination of oral deferasirox and subcutaneous deferoxamine for 6 months. Reduction in iron overload, as measured by a reduction in the serum ferritin after completion of the treatment, will be the primary outcome measure. Reduction in liver and cardiac iron content as measured by T2* MRI and the side effect profile of trial medications are the secondary outcome measures. ETHICS AND DISSEMINATION: Ethical approval for the study has been obtained from the Ethics Committee of the Faculty of Medicine, University of Kelaniya (Ref. P/06/02/2023). The trial results will be disseminated in scientific publications in reputed journals. TRIAL REGISTRATION NUMBER: The trial is registered in the Sri Lanka Clinical Trials Registry (Ref: SLCTR/2023/010).


Assuntos
Sobrecarga de Ferro , Talassemia beta , Adulto , Adolescente , Humanos , Deferasirox/uso terapêutico , Deferiprona/uso terapêutico , Desferroxamina/uso terapêutico , Talassemia beta/complicações , Talassemia beta/tratamento farmacológico , Benzoatos/uso terapêutico , Benzoatos/efeitos adversos , Triazóis/efeitos adversos , Piridonas , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Quelantes de Ferro/efeitos adversos , Ferro/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Br J Haematol ; 204(5): 2049-2056, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38343073

RESUMO

Iron overload from repeated transfusions has a negative impact on cardiac function, and iron chelation therapy may help prevent cardiac dysfunction in transfusion-dependent patients with myelodysplastic syndromes (MDS). TELESTO (NCT00940602) was a prospective, placebo-controlled, randomised study to evaluate the iron chelator deferasirox in patients with low- or intermediate-1-risk MDS and iron overload. Echocardiographic parameters were collected at screening and during treatment. Patients receiving deferasirox experienced a significant decrease in the composite risk of hospitalisation for congestive heart failure (CHF) or worsening of cardiac function (HR = 0.23; 95% CI: 0.05, 0.99; nominal p = 0.0322) versus placebo. No significant differences between the arms were found in left ventricular ejection fraction, ventricular diameter and mass or pulmonary artery pressure. The absolute number of events was low, but the enrolled patients were younger than average for patients with MDS, with no serious cardiac comorbidities and a modest cardiovascular risk profile. These results support the effectiveness of deferasirox in preventing cardiac damage caused by iron overload in this patient population. Identification of patients developing CHF is challenging due to the lack of distinctive echocardiographic features. The treatment of iron overload may be important to prevent cardiac dysfunction in these patients, even those with moderate CHF risk.


Assuntos
Deferasirox , Quelantes de Ferro , Sobrecarga de Ferro , Síndromes Mielodisplásicas , Humanos , Deferasirox/uso terapêutico , Síndromes Mielodisplásicas/terapia , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/complicações , Masculino , Feminino , Quelantes de Ferro/uso terapêutico , Pessoa de Meia-Idade , Idoso , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/tratamento farmacológico , Estudos Prospectivos , Benzoatos/uso terapêutico , Benzoatos/efeitos adversos , Insuficiência Cardíaca/etiologia , Reação Transfusional/etiologia , Ecocardiografia , Adulto , Idoso de 80 Anos ou mais , Triazóis/uso terapêutico , Triazóis/efeitos adversos , Transfusão de Sangue
12.
Rev Invest Clin ; 76(1): 18-28, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38262366

RESUMO

Background: Iron overload is frequent in patients with chronic liver disease, associated with shorter survival after liver transplantation in patients with hereditary hemochromatosis. Its effect on patients without hereditary hemochromatosis is unclear. The aim of the study was to study the clinical impact of iron overload in patients who underwent liver transplantation at an academic tertiary referral center. Methods: We performed a retrospective cohort study including all patients without hereditary hemochromatosis who underwent liver transplantation from 2015 to 2017 at an academic tertiary referral center in Mexico City. Explant liver biopsies were reprocessed to obtain the histochemical hepatic iron index, considering a score ≥ 0.15 as iron overload. Baseline characteristics were compared between patients with and without iron overload. Survival was estimated using the Kaplan-Meier method, compared with the log-rank test and the Cox proportional hazards model. Results: Of 105 patients included, 45% had iron overload. Viral and metabolic etiologies, alcohol consumption, and obesity were more frequent in patients with iron overload than in those without iron overload (43% vs. 21%, 32% vs. 22%, p = 0.011; 34% vs. 9%, p = 0.001; and 32% vs. 12%, p = 0.013, respectively). Eight patients died within 90 days after liver transplantation (one with iron overload). Complication rate was higher in patients with iron overload versus those without iron overload (223 vs. 93 events/100 personmonths; median time to any complication of 2 vs. 3 days, p = 0.043), without differences in complication type. Fatality rate was lower in patients with iron overload versus those without iron overload (0.7 vs. 4.5 deaths/100 person-months, p = 0.055). Conclusion: Detecting iron overload might identify patients at risk of early complications after liver transplantation. Further studies are required to understand the role of iron overload in survival.


Assuntos
Hemocromatose , Sobrecarga de Ferro , Hepatopatias , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Hemocromatose/complicações , Hemocromatose/epidemiologia , Hemocromatose/patologia , Estudos Retrospectivos , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/complicações , Hepatopatias/complicações , Hepatopatias/metabolismo , Hepatopatias/patologia , Fígado/metabolismo
13.
Blood Rev ; 64: 101165, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38182489

RESUMO

α-Thalassemia is an inherited blood disorder characterized by decreased synthesis of α-globin chains that results in an imbalance of α and ß globin and thus varying degrees of ineffective erythropoiesis, decreased red blood cell (RBC) survival, chronic hemolytic anemia, and subsequent comorbidities. Clinical presentation varies depending on the genotype, ranging from a silent or mild carrier state to severe, transfusion-dependent or lethal disease. Management of patients with α-thalassemia is primarily supportive, addressing either symptoms (eg, RBC transfusions for anemia), complications of the disease, or its transfusion-dependence (eg, chelation therapy for iron overload). Several novel therapies are also in development, including curative gene manipulation techniques and disease modifying agents that target ineffective erythropoiesis and chronic hemolytic anemia. This review of α-thalassemia and its various manifestations provides practical information for clinicians who practice beyond those regions where it is found with high frequency.


Assuntos
Doenças Hematológicas , Sobrecarga de Ferro , Talassemia alfa , Talassemia beta , Humanos , Talassemia beta/terapia , Talassemia alfa/diagnóstico , Talassemia alfa/genética , Talassemia alfa/terapia , Eritropoese , Transfusão de Eritrócitos , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/terapia
14.
BMJ Case Rep ; 17(1)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38272521

RESUMO

Crohn's disease patients often need regular home parenteral nutrition (HPN) for intestinal failure due to multiple intestinal resections. Trace elements are necessary for long-term HPN but the requirement volume of iron is undetermined. We describe three patients with Crohn's disease with short bowel syndrome (SBS) who had iron overload as a result of long-term HPN including iron. Serum ferritin level was significantly decreased through depleting intravenous iron administration in all cases. One patient needed regular insulin injection and phlebotomy for diabetes mellitus due to hemochromatosis, and intravenous iron administration had a significant impact on the patient's health. Long-term routine intravenous iron administration should be cautious in SBS patients to avoid the overload.


Assuntos
Doença de Crohn , Sobrecarga de Ferro , Nutrição Parenteral no Domicílio , Síndrome do Intestino Curto , Oligoelementos , Humanos , Doença de Crohn/complicações , Doença de Crohn/cirurgia , Oligoelementos/uso terapêutico , Síndrome do Intestino Curto/complicações , Síndrome do Intestino Curto/terapia , Ferro , Sobrecarga de Ferro/etiologia
15.
Blood Transfus ; 22(1): 75-85, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37146300

RESUMO

BACKGROUND: In transfusion-dependent thalassemia patients who started regular transfusions in early childhood, we prospectively and longitudinally evaluated the efficacy on pancreatic iron of a combined deferiprone (DFP) + desferrioxamine (DFO) regimen versus either oral iron chelator as monotherapy over a follow-up of 18 months. MATERIALS AND METHODS: We selected patients consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia network who received a combined regimen of DFO+DFP (No.=28) or DFP (No.=61) or deferasirox (DFX) (No.=159) monotherapy between the two magnetic resonance imaging scans. Pancreatic iron overload was quantified by the T2* technique. RESULTS: At baseline no patient in the combined treatment group had a normal global pancreas T2* (≥26 ms). At follow-up the percentage of patients who maintained a normal pancreas T2* was comparable between the DFP and DFX groups (57.1 vs 70%; p=0.517).Among the patients with pancreatic iron overload at baseline, global pancreatic T2* values were significantly lower in the combined DFO+DFP group than in the DFP or DFX groups. Since changes in global pancreas T2* values were negatively correlated with baseline pancreas T2* values, the percent changes in global pancreas T2* values, normalized for the baseline values, were considered. The percent changes in global pancreas T2* values were significantly higher in the combined DFO+DFP group than in either the DFP (p=0.036) or DFX (p=0.030) groups. DISCUSSION: In transfusion-dependent patients who started regular transfusions in early childhood, combined DFP+DFO was significantly more effective in reducing pancreatic iron than was either DFP or DFX.


Assuntos
Sobrecarga de Ferro , Talassemia , Talassemia beta , Humanos , Pré-Escolar , Ferro/uso terapêutico , Deferasirox , Deferiprona/uso terapêutico , Desferroxamina/uso terapêutico , Quelantes de Ferro/uso terapêutico , Piridonas/uso terapêutico , Talassemia beta/diagnóstico por imagem , Talassemia beta/tratamento farmacológico , Benzoatos/uso terapêutico , Triazóis/uso terapêutico , Quimioterapia Combinada , Sobrecarga de Ferro/diagnóstico por imagem , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Pâncreas/diagnóstico por imagem
16.
Pediatr Hematol Oncol ; 41(4): 251-259, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38088332

RESUMO

Patients with beta-thalassemia major require lifelong and frequent red blood cell transfusions for survival, impacting their quality of life and life expectancy. This treatment approach poses risks of organ damage, iron overload, and increased transfusion-transmitted diseases. N-acetylcysteine (NAC) has been studied for its potential antioxidant effects on hemoglobin stability, aiming to reduce the burden of red blood cell transfusions. To explore this possibility further, we conducted a quasi-experimental study involving 35 individuals with thalassemia major over six months All subjects were already receiving iron chelators and blood transfusions. They were given a daily oral dose of 10 mg/kg NAC for three months. After three months of treatment with NAC, the serum levels of ferritin and liver enzymes (SGOT and SGPT) did not show significant changes (p = 0.35, p = 0.352, and p = 0.686, respectively). However, the red blood cell transfusion burden was significantly reduced in all patients after NAC therapy (p = 0.029), with no corresponding decrease in serum hemoglobin levels (p = 0.931), indicating maintained hemoglobin concentration despite reduced transfusion volume. The study indicates that NAC can effectively decrease the burden of red blood cell transfusions without significant toxicity in these patients. This finding suggests the potential for NAC as a cost-effective and manageable treatment option for these patients. A larger clinical trial with more robust statistical methods could further confirm these results and pave the way for using NAC as a valuable therapeutic agent for managing beta-thalassemia major patients.


Assuntos
Sobrecarga de Ferro , Talassemia beta , Humanos , Transfusão de Eritrócitos , Acetilcisteína/uso terapêutico , Qualidade de Vida , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Hemoglobinas/análise
17.
Ann Hematol ; 103(5): 1423-1433, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37405444

RESUMO

Coronavirus disease 19 (COVID-19) is an infectious disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) causing acute systemic disorders and multi-organ damage. ß-thalassemia (ß-T) is an autosomal recessive disorder leading to the development of anemia. ß-T may lead to complications such as immunological disorders, iron overload, oxidative stress, and endocrinopathy. ß-T and associated complications may increase the risk of SARS-CoV-2, as inflammatory disturbances and oxidative stress disorders are linked with COVID-19. Therefore, the objective of the present review was to elucidate the potential link between ß-T and COVID-19 regarding the underlying comorbidities. The present review showed that most of the ß-T patients with COVID-19 revealed mild to moderate clinical features, and ß-T may not be linked with Covid-19 severity. Though patients with transfusion-dependent ß-T (TDT) develop less COVID-19 severity compared to non-transfusion-depend ß-T(NTDT), preclinical and clinical studies are recommended in this regard.


Assuntos
COVID-19 , Sobrecarga de Ferro , Talassemia beta , Humanos , Talassemia beta/complicações , Talassemia beta/epidemiologia , Talassemia beta/terapia , COVID-19/complicações , SARS-CoV-2 , Transfusão de Sangue , Sobrecarga de Ferro/etiologia
18.
Auris Nasus Larynx ; 51(2): 271-275, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37903661

RESUMO

OBJECTIVE: The role of iron chelation in causing hearing loss (HL) is still unclear. The present study assessed the prevalence of HL among transfusion-dependent thalassemia (TDT) patients who underwent audiological follow-up over a 20-year period. METHODS: We retrospectively analyzed clinical records and audiological tests from January 1990 (T0) to December 2022 (T22) of a group of TDT patients who received iron chelation therapy with deferoxamine (DFO), deferiprone (DFP) or deferasirox (DFX), in monotherapy or as part of combination therapy. RESULTS: A total of 42 adult TDT patients (18 male, 24 female; age range: 41-55 years; mean age: 49.2 ± 3.7 years) were included in the study. At the T22 assessment, the overall prevalence of sensorineural HL was 23.8 % (10/42). When patients were stratified into two groups, with and without ototoxicity, no differences were observed for sex, age, BMI, creatinine level, pre-transfusional hemoglobin, start of transfusions, cardiac or hepatic T2 MRI; only ferritin serum values and duration of chelation were significantly higher (p = 0.02 and p = 0.01, respectively) in patients with hearing impairment in comparison to those with normal hearing. CONCLUSION: This study with long-term follow-up suggests that iron chelation therapy might induce ototoxicity; therefore, a long and accurate audiological follow-up should be performed in TDT patients.


Assuntos
Sobrecarga de Ferro , Ototoxicidade , Talassemia beta , Adulto , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Talassemia beta/complicações , Talassemia beta/tratamento farmacológico , Talassemia beta/epidemiologia , Deferasirox/uso terapêutico , Deferiprona/uso terapêutico , Desferroxamina/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/epidemiologia , Sobrecarga de Ferro/etiologia , Seguimentos , Estudos Retrospectivos , Ototoxicidade/complicações , Ototoxicidade/tratamento farmacológico , Benzoatos/uso terapêutico , Triazóis/uso terapêutico , Piridonas/uso terapêutico , Quelantes de Ferro/uso terapêutico , Ferro/uso terapêutico , Audição
19.
World Neurosurg ; 184: e25-e31, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37979684

RESUMO

BACKGROUND: Hereditary hemochromatosis (HH) is a common autosomal recessive disorder. This disease affects gut iron transport, leading to iron overload, which affects immune function, coagulation mechanics, and bone health. Within the spine, HH contributes to decreased bone mineral density and accelerated intervertebral disc degeneration. The purpose of this study was to discover the differences in the rates of common 90-day postoperative complications and 1-year and 2-year surgical outcomes in patients with and without HH after anterior cervical discectomy and fusion (ACDF). METHODS: Using the PearlDiver database, patients with active diagnoses of HH before ACDF were matched to patients without HH using a 1:5 ratio on the basis of age, sex, body mass index, and comorbidities. Postoperative complications were assessed at 90 days, and 1-year and 2-year surgical outcomes were assessed. All outcomes and complications were analyzed using multivariate logistic regression with significance achieved at P < 0.05. RESULTS: Patients with HH had significantly higher rates of 1-year and 2-year reoperation rates compared with patients without HH (29.19% vs. 3.94% and 37.1% vs. 5.93%, respectively; P < 0.001). The rates of 90-day postoperative complications significantly increased in patients with HH including dysphagia, pneumonia, cerebrovascular accident, deep vein thrombosis, acute kidney injury, urinary tract infection, hyponatremia, surgical site infection, iatrogenic deformity, emergency department visit, and hospital readmission. CONCLUSIONS: Patients with HH undergoing ACDF showed increased 90-day postoperative complications and significantly increased rates of 1-year and 2-year reoperation compared with patients without HH. These findings suggest that iron overload may contribute to adverse outcomes in patients with HH undergoing 1-level and 2-level ACDF.


Assuntos
Hemocromatose , Sobrecarga de Ferro , Fusão Vertebral , Humanos , Hemocromatose/complicações , Hemocromatose/cirurgia , Estudos Retrospectivos , Vértebras Cervicais/cirurgia , Discotomia/efeitos adversos , Infecção da Ferida Cirúrgica/etiologia , Sobrecarga de Ferro/etiologia , Fusão Vertebral/efeitos adversos , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
20.
J Clin Ultrasound ; 52(2): 124-130, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37933208

RESUMO

PURPOSE: To evaluate correlation between serum iron parameters and liver T2* value in hemodialysis patients with iron overload due to parenteral iron therapy. MATERIALS AND METHODS: We evaluated 30 hemodialysis patients using a multiecho T2*-weighted MRI sequence. Age, sex, duration of dialysis, iron and erythropoietin doses taken in the past year, and serum iron parameters were recorded. Liver T2* values were averaged from three distinct liver regions. A T2* value of 33 ± 7 ms is considered normal. Declines below 24, 21, and 14 ms signify iron overload grades 1, 2, and 3, respectively. RESULTS: There was no statistically significant difference comparing the measurements of 3 different ROIs (p > 0.05). A total of 23 patients (76.6%) had iron overload. Serum ferritin levels of patients with iron overload were significantly higher than those without iron overload (687.25 [186.5-1489] ng/mL vs. 371.25 [127.5-542.5] ng/mL, p = 0.008). No linear correlation was observed between age, dialysis duration, serum iron metrics, medication doses, and T2* values. Likewise, no significant differences were found among patients based on iron overload status or its grades concerning these parameters. CONCLUSION: While standard serum markers might overlook iron overload, elevated ferritin levels are promising. MRI reliably detects iron overload in patients receiving parenteral iron.


Assuntos
Ferritinas , Sobrecarga de Ferro , Humanos , Sobrecarga de Ferro/diagnóstico por imagem , Sobrecarga de Ferro/etiologia , Ferro/metabolismo , Fígado/diagnóstico por imagem , Fígado/metabolismo , Diálise Renal/efeitos adversos , Imageamento por Ressonância Magnética
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