RESUMO
Anemia of inflammation (AI) is a very frequent clinical condition affecting globally more than a billion people with chronic inflammatory disorders, such as chronic kidney disease, heart failure, and inflammatory bowel disease. It is usually associated with iron deficiency (ID), which imposes a severe additional burden on the recovery from the primary disease. The pathophysiology of iron dysregulation that may ultimately lead to absolute iron deficiency anemia (IDA) during inflammation is multifactorial and includes reduced iron absorption in the bowel, iron retention in macrophages of the reticuloendothelial system, reduction in circulatory halflife of erythrocytes, inadequate production and activity of erythropoietin, and impaired proliferation and differentiation of erythroid progenitor cells. These result in hypoferremia and iron-restricted erythropoiesis. AI is mostly mild to moderate, normochromic and normocytic with normal or even increased ferritin levels. The current treatment options for AI include iron replacement therapy, treatment with erythropoiesisstimulating agents, and red blood cell transfusion. ID management is based on oral or intravenous iron preparations. Given the pathophysiology, treatment with oral iron, although widely used, presents several limitations that impact its effectiveness in patients with chronic inflammatory conditions. Instead, intravenous iron preparations are a valuable option for patients with chronic inflammatory diseases, as they overcome reduced bowel absorption. Novel therapeutic approaches include downregulation of hepcidin synthesis and function, and stabilization of the hypoxiainducible factor via inhibition of prolyl hydroxylase domain. Several studies in vitro and in vivo are ongoing; however, the results in humans are still elusive.
Assuntos
Anemia , Ferro , Humanos , Anemia/tratamento farmacológico , Doença Crônica , Eritropoese , InflamaçãoRESUMO
BACKGROUND: Iron overload-related heart failure is the principal cause of death in transfusion dependent patients, including those with Thalassemia Major. Linking cardiac siderosis measured by T2* to therapy improves outcomes. T1 mapping can also measure iron; preliminary data suggests it may have higher sensitivity for iron, particularly for early overload (the conventional cut-point for no iron by T2* is 20ms, but this is believed insensitive). We compared T1 mapping to T2* in cardiac iron overload. METHODS: In a prospectively large single centre study of 138 Thalassemia Major patients and 32 healthy controls, we compared T1 mapping to dark blood and bright blood T2* acquired at 1.5T. Linear regression analysis was used to assess the association of T2* and T1. A "moving window" approach was taken to understand the strength of the association at different levels of iron overload. RESULTS: The relationship between T2* (here dark blood) and T1 is described by a log-log linear regression, which can be split in three different slopes: 1) T2* low, <20ms, r2 = 0.92; 2) T2* = 20-30ms, r2 = 0.48; 3) T2*>30ms, weak relationship. All subjects with T2*<20ms had low T1; among those with T2*>20ms, 38% had low T1 with most of the subjects in the T2* range 20-30ms having a low T1. CONCLUSIONS: In established cardiac iron overload, T1 and T2* are concordant. However, in the 20-30ms T2* range, T1 mapping appears to detect iron. These data support previous suggestions that T1 detects missed iron in 1 out of 3 subjects with normal T2*, and that T1 mapping is complementary to T2*. The clinical significance of a low T1 with normal T2* should be further investigated.
Assuntos
Sangue/diagnóstico por imagem , Técnicas de Imagem Cardíaca/métodos , Sobrecarga de Ferro/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Talassemia beta/diagnóstico por imagem , Adulto , Feminino , Humanos , Sobrecarga de Ferro/fisiopatologia , Modelos Lineares , Masculino , Estudos Prospectivos , Talassemia beta/fisiopatologiaRESUMO
Although its prevalence is unknown, liver involvement by sickle cell disease is not uncommon and encompasses different clinical spectra including non cholestatic and cholestatic disorders. Few data have been provided on chronic sickle cell intrahepatic cholestasis (SCIC) clinical course, although cirrhosis has been reported in sickle cell disease. However, no effective therapeutic approaches have been recognized either to prevent or treat this condition. Here we present two cases of adult sickle cell disease patients with decompensated cirrhosis. Their liver biopsies showed sickle cell thrombi within the hepatic sinusoids. Despite erythroexchange (EEX) transfusions, both patients suffered from major sickle cell disease-related events, suggesting that EEX transfusions may not be enough to impact on advanced liver involvement by sickle cell disease.
Assuntos
Anemia Falciforme , Transfusão de Eritrócitos , Cirrose Hepática , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/patologia , Anemia Falciforme/terapia , Feminino , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Cirrose Hepática/terapia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: Plasma markers in addition to serum ferritin (SF) may be useful for the assessment of iron overload; however, predictive utility may differ depending on underlying, transfusion-dependent, anemias. METHODS: Data were collected before and after 1 year of deferasirox treatment (end of study; EOS) from the large, 1-year EPIC (Evaluation of Patients' Iron Chelation with Exjade(®) ) study. Trends were evaluated between liver iron concentration (LIC), transferrin saturation (TfSat), predose labile plasma iron (LPI) and their relationship to SF categories in 1530 patients: thalassemia major (TM; n = 1114), myelodysplastic syndromes (MDS, n = 336), and sickle-cell disease (SCD, n = 80). RESULTS: Baseline and EOS SF values showed a clear and similar relationship to LIC for all disease groups. TfSat also showed a relationship to SF, most clearly in patients with SCD, where TfSat was lowest in the lowest relative SF category. Unlike SF or LIC, TfSat did not decrease at EOS in any disease group. Baseline LPI was raised in TM and MDS, but not in patients with SCD, decreasing at EOS in both patient groups. After 1 year of chelation therapy, there was a significant trend for greater LPI reduction in patients with TM achieving LIC <7 mg Fe/g dw (P = 0.0137). CONCLUSIONS: Despite limitations, SF showed the clearest relationship, of the plasma markers evaluated, to LIC before and after 1 year of deferasirox in patients with TM, MDS, and SCD. In patients with TM, changes in LPI with chelation show a significant relationship to EOS LIC and may provide an additional indicator of chelation response (clinicaltrials.gov identifier: NCT00171821).
Assuntos
Anemia , Benzoatos/administração & dosagem , Ferritinas/sangue , Sobrecarga de Ferro , Ferro/sangue , Transferrina/metabolismo , Triazóis/administração & dosagem , Anemia/sangue , Anemia/tratamento farmacológico , Biomarcadores/sangue , Deferasirox , Feminino , Seguimentos , Humanos , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/tratamento farmacológico , MasculinoRESUMO
BACKGROUND AND AIM: Iron is the most abundant metal in mammalian cells, and plays a pivotal role in many metabolic processes. Dysregulated iron homeostasis is involved in the cause of a number of pathological processes including renal diseases. METHODS AND RESULTS: Longitudinal MRI scans of salt-loaded spontaneously hypertensive stroke-prone rats (SHRSP), an animal model that spontaneously develops hypertensive nephropathy, showed a decrease in renal and hepatic T2 SI (a sign of iron accumulation) of, respectively, 42.3â±â2.5% (Pâ<â0.01) and 60.4â±â15.1% (Pâ<â0.01) in comparison with SHRSP fed a standard diet. This was accompanied by the development of renal inflammation and oxidative stress (as evaluated by immunohistochemical and proteomic analyses), mitochondrial dysfunction, massive proteinuria and sustained intravascular hemolysis with the subsequent depletion of plasma haptoglobin, which was responsible for the renal uptake of hemoglobin and iron accumulation. In order to investigate the role of iron in these pathological processes, we subcutaneously treated the salt-loaded rats with the iron chelator deferoxamine (200âmg/kg per day). The pharmacological treatment prevented iron tissue accumulation, as indicated by the increase in renal and hepatic T2 SI of, respectively, 120.0â±â10.1% (Pâ<â0.01) and 73.9â±â4.4% (Pâ<â0.01) in comparison with salt-loaded rats treated with vehicle alone. Deferoxamine also preserved renal morphology and function, the renal infiltration of ED-1-positive macrophages/monocytes, and the expression of MCP-1 and TGF-ß mRNA, reduced the level of reactive oxygen species, and improved the activity of mitochondrial cytochrome c oxidase. CONCLUSION: These findings suggest that iron dysmetabolism is involved in the development of hypertensive nephropathy in SHRSP.
Assuntos
Hipertensão Renal/metabolismo , Ferro/metabolismo , Ferro/fisiologia , Nefrite/metabolismo , Animais , Pressão Sanguínea , Desferroxamina/farmacologia , Modelos Animais de Doenças , Hemólise/fisiologia , Homeostase , Hipertensão Renal/etiologia , Rim/fisiopatologia , Masculino , Modelos Animais , Nefrite/etiologia , Estresse Oxidativo , Proteinúria/etiologia , Proteinúria/metabolismo , Proteômica , Ratos , Ratos Endogâmicos SHR , Espécies Reativas de Oxigênio/metabolismo , Cloreto de Sódio na Dieta/administração & dosagem , Cloreto de Sódio na Dieta/metabolismo , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia , Fator de Crescimento Transformador beta/metabolismoRESUMO
PURPOSE OF REVIEW: The aim is to overview recent evidence on consequences, assessment, and management of iron overload in transfusion-independent patients with ß-thalassemia intermedia. RECENT FINDINGS: Despite their transfusion-independence, ß-thalassemia intermedia patients can still accumulate iron due to increased intestinal absorption. Recent observational studies show that iron burden in this group of patients can ultimately reach considerably high thresholds, and leads to a variety of serious morbidities involving the liver, endocrine glands, and arguably the vascular system. The diagnosis of iron overload in this patient population can follow established guidelines from ß-thalassemia major patients, although with careful interpretation of spot serum ferritin levels. Data from a recent randomized clinical trial demonstrated the efficacy and safety of iron chelation therapy in decreasing liver iron concentration in this group of patients, which may ultimately help in reducing morbidity risk. SUMMARY: Iron overload in transfusion-independent patients with ß-thalassemia intermedia deserves careful attention, and prompt diagnosis and management are recommended.
Assuntos
Sobrecarga de Ferro/etiologia , Talassemia beta/complicações , Humanos , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/terapia , Talassemia beta/terapiaRESUMO
BACKGROUND: Anemia is a common complication of chronic kidney disease (CKD) that negatively impacts the quality of life and is associated with numerous adverse outcomes. Excess levels of the iron regulatory hormone hepcidin are thought to contribute to anemia in CKD patients by decreasing iron availability from the diet and from body stores. Adenine treatment in rats has been proposed as an animal model of anemia of CKD with high hepcidin levels that mirrors the condition in human patients. METHODS: We developed a modified adenine-induced kidney disease model with a higher survival rate than previously reported models, while maintaining persistent kidney disease and anemia. We then tested whether the small molecule bone morphogenetic protein (BMP) inhibitor LDN-193189, which was previously shown to lower hepcidin levels in rodents, mobilized iron into the plasma and improved iron-restricted erythropoiesis in this model. RESULTS: Adenine-treated rats exhibited increased hepatic hepcidin mRNA, decreased serum iron, increased spleen iron content, low hemoglobin (Hb) and inappropriately low erythropoietin (EPO) levels relative to the degree of anemia. LDN-193189 administration to adenine-treated rats lowered hepatic hepcidin mRNA, mobilized stored iron into plasma and increased Hb content of reticulocytes. CONCLUSIONS: Our data suggest that hepcidin lowering agents may provide a new therapeutic strategy to improve iron availability for erythropoiesis in CKD.
Assuntos
Adenina/toxicidade , Anemia Ferropriva/tratamento farmacológico , Modelos Animais de Doenças , Eritrócitos/efeitos dos fármacos , Hepcidinas/metabolismo , Ferro/metabolismo , Nefropatias/complicações , Pirazóis/farmacologia , Pirimidinas/farmacologia , Anemia Ferropriva/sangue , Anemia Ferropriva/etiologia , Animais , Anti-Infecciosos/antagonistas & inibidores , Anti-Infecciosos/metabolismo , Western Blotting , Proteínas Morfogenéticas Ósseas/antagonistas & inibidores , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Ensaio de Imunoadsorção Enzimática , Eritrócitos/citologia , Eritrócitos/metabolismo , Eritropoese/efeitos dos fármacos , Hepcidinas/antagonistas & inibidores , Humanos , Nefropatias/sangue , Nefropatias/induzido quimicamente , Masculino , RNA Mensageiro/genética , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Genomic DNA of 3 patients, born as healthy carriers and developing a late-onset severe transfusion-dependent beta-thalassemia major was studied by high-density genome wide SNP array analysis. A mosaic loss of heterozygosity for almost the entire 11p was found, not attributable to deletions but involving mosaicism for segmental paternal isodisomy of 11p. Mitotic recombination leading to mosaic segmental uniparental isodisomy on chromosome 11p in multiple tissues has been described as a molecular disease mechanism for a subset of sporadic Beckwith-Wiedemann syndrome cases. A similar mechanism also seems to be involved in causing late-onset disease in carriers of recessive mutations in other genes located in 11p, such as late-onset beta-thalassemia major and sickle cell disease. We suggest that the loss of maternally imprinted IGF-2 and H19 genes may account for the selective advantage of hematopoietic cells containing this segmental paternal isodisomy of 11p carrying the ß-thalassemia mutation.
Assuntos
Mosaicismo , Dissomia Uniparental , Talassemia beta/genética , Talassemia beta/metabolismo , Adolescente , Adulto , Fatores Etários , Alelos , Criança , Cromossomos Humanos Par 11 , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Mutação , Linhagem , Polimorfismo de Nucleotídeo Único , Adulto Jovem , Globinas beta/genética , Talassemia beta/diagnósticoRESUMO
Iron overload due to increased intestinal iron absorption represents an important clinical problem in patients with non-transfusion-dependent thalassemia (NTDT), particularly as they advance in age. Current models for iron metabolism in patients with beta (ß)-thalassemia intermedia (TI) suggest that suppression of serum hepcidin results in increased iron absorption and release of iron from the reticuloendothelial system, leading to depletion of macrophage iron, relatively low levels of serum ferritin, and liver iron loading. The clinical consequences of iron overload in patients with NTDT are multifactorial and include endocrinopathy, bone disease, thromboembolism, pulmonary hypertension, cerebrovascular and neuronal damage, liver fibrosis or cirrhosis, and increased risk of hepatocellular carcinoma. Although serum ferritin levels correlate with liver iron concentration (LIC), they underestimate iron load in these patients compared with transfusion-dependent patients with equivalent LIC. Therefore, direct measurement of LIC is recommended with chelation therapy as indicated.
Assuntos
Sobrecarga de Ferro/metabolismo , Ferro/metabolismo , Talassemia/metabolismo , Transfusão de Sangue , Humanos , Absorção Intestinal , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológicoRESUMO
Beta-thalassemia intermedia (TI) is associated with a variety of serious clinical complications that require proactive and comprehensive management. These include skeletal deformities and osteopenia, compensatory extramedullary hematopoiesis and tumor formation, progressive splenomegaly, a hypercoagulable state resulting in thromboembolic events and pulmonary hypertension, and increased gastrointestinal iron absorption that often results in nontransfusional iron overload and liver damage. Although TI is generally considered a non-transfusion-dependent thalassemia, transfusion therapy may be an important part of the comprehensive management of this disease. This review describes the current state of the art for medical management of TI, with particular focus on the roles of splenectomy, transfusion, and iron chelation therapy.
Assuntos
Talassemia beta/terapia , Transfusão de Sangue , Humanos , Quelantes de Ferro/uso terapêutico , Esplenectomia , Talassemia beta/tratamento farmacológico , Talassemia beta/cirurgiaRESUMO
Transmembrane Protease, Serine 6 (TMPRSS6) has an important role in iron homeostasis and its mutations, performed in TMPRSS6-deficient mice, have been recently associated with iron-refractory iron deficiency anaemia (IRIDA). Several variants of TMPRSS6 have been already identified; however the role of polymorphisms and TMPRSS6 haplotypes, causing iron deficiency anaemia, have not yet been investigated. This study sequenced the TMPRSS6 gene in 16 subjects with IRIDA phenotype and identified 27 DNA polymorphisms. Eight single nucleotide polymorphisms and four haplotypes were significantly associated with iron-refractory anaemia (P < 0·001). Our preliminary results suggest a possible association between specific haplotypes of TMPRSS6 and IRIDA.
Assuntos
Anemia Ferropriva/genética , Proteínas de Membrana/genética , Mutação , Serina Endopeptidases/genética , Adulto , Feminino , Predisposição Genética para Doença , Variação Genética , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Our understanding of the molecular and pathophysiological mechanisms underlying the disease process in patients with thalassemia intermedia (TI) has substantially increased over the past decade. TI encompasses a wide clinical spectrum of beta-thalassemia phenotypes. Some TI patients are asymptomatic until adult life, whereas others are symptomatic from as young as 2 years. A number of clinical complications commonly associated with TI are rarely seen in thalassemia major, including extramedullary hematopoiesis, leg ulcers, gallstones, thrombosis, and pulmonary hypertension. There are a number of options currently available for managing patients with TI, including transfusion therapy, iron chelation therapy, modulation of fetal hemoglobin production, and hematopoietic stem cell transplantation. However, at present, there are no clear guidelines for an orchestrated optimal treatment plan.
Assuntos
Talassemia beta/complicações , Talassemia beta/terapia , Anemia Hemolítica , Eritropoese , Humanos , Sobrecarga de Ferro , Mutação , Globinas beta/genética , Talassemia beta/genéticaRESUMO
Chronic iron overload from frequent blood transfusions to treat patients with severe anemias leads to significant morbidity and mortality. Although desferrioxamine, the current standard of care, is an effective iron chelator with long-term evidence, it requires tedious subcutaneous infusion that reflects negatively on patient compliance. Deferiprone opened the horizon for an era of oral iron chelators. Although collective evidence proved its efficacy, safety issues are still of high concern and require regular monitoring. The experience with these two drugs helps better delineate the optimal goals of iron chelation therapy and the ideal iron chelator.
Assuntos
Terapia por Quelação/métodos , Desferroxamina/uso terapêutico , Piridonas/uso terapêutico , Deferiprona , Desferroxamina/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Quelantes de Ferro/efeitos adversos , Quelantes de Ferro/uso terapêutico , Piridonas/efeitos adversos , Resultado do TratamentoRESUMO
The highest approved dose of deferasirox is currently 30 mg/kg per d in many countries; however, some patients require escalation above 30 mg/kg per d to achieve their therapeutic goals. This retrospective analysis investigated the efficacy (based on change in serum ferritin levels) and safety of deferasirox >30 mg/kg per d in adult and paediatric patients with transfusion-dependent anaemias, including beta-thalassaemia, sickle cell disease and the myelodysplastic syndromes. In total, 264 patients pooled from four clinical trials received doses of >30 mg/kg per d; median exposure to deferasirox >30 mg/kg per d was 36 weeks. In the overall population there was a statistically significant median decrease in serum ferritin of 440 microg/l (P < 0.0001) from pre-dose-escalation to the time-of-analysis; significant decreases were also observed in adult and paediatric patients, as well as beta-thalassaemia patients. The adverse event profile in patients who received deferasirox doses of >30 mg/kg per d was consistent with previously published data. There was no worsening of renal or liver function following dose escalation. Deferasirox >30 mg/kg per d effectively reduced iron burden to levels lower than those achieved prior to dose escalation in patients with transfusion-dependent anaemias. This has important implications for patients who are heavily transfused and may require higher doses to reduce body iron burden.
Assuntos
Anemia/terapia , Benzoatos/uso terapêutico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Reação Transfusional , Triazóis/uso terapêutico , Adolescente , Adulto , Benzoatos/administração & dosagem , Benzoatos/efeitos adversos , Criança , Pré-Escolar , Creatinina/sangue , Deferasirox , Esquema de Medicação , Feminino , Ferritinas/sangue , Humanos , Quelantes de Ferro/administração & dosagem , Quelantes de Ferro/efeitos adversos , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Triazóis/administração & dosagem , Triazóis/efeitos adversos , Adulto JovemRESUMO
Non-transferrin-bound iron (NTBI) was evaluated as an index of iron overload in a cross-sectional randomised study in 74 non-transfused patients with thalassaemia intermedia (TI). Mean NTBI (2.92 +/- 3.43 micromol/l), serum ferritin (1023 +/- 780 ng/ml) and liver iron concentration (LIC; 9.0 +/- 7.4 mg Fe/g dry weight) were increased above reference-range levels. Significant positive correlations occurred between mean NTBI and LIC (Pearson correlation 0.36; P = 0.002) and serum ferritin (Pearson correlation 0.421; P < 0.0001); with higher levels observed in splenectomised patients. NTBI assessment has potential as a simple reliable approach to determining iron status in TI.
Assuntos
Sobrecarga de Ferro/diagnóstico , Ferro/sangue , Talassemia/sangue , Adolescente , Adulto , Biomarcadores/sangue , Criança , Estudos Transversais , Feminino , Ferritinas/sangue , Humanos , Ferro/análise , Sobrecarga de Ferro/sangue , Fígado/química , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Esplenectomia , Adulto JovemRESUMO
Our understanding of the molecular and pathophysiological mechanisms underlying the disease process in patients with thalassaemia intermedia (TI) has substantially increased over the past decade. TI encompasses a wide clinical spectrum of beta-thalassaemia phenotypes. Some TI patients are asymptomatic until adult life, whereas others are symptomatic from as young as 2 years of age. A number of clinical complications commonly associated with TI are rarely seen in thalassaemia major, including extramedullary hematopoiesis, leg ulcers, gallstones, thrombosis and pulmonary hypertension. There are a number of options currently available for managing patients with TI, including transfusion therapy, iron chelation therapy, modulation of foetal haemoglobin production and haematopoietic stem cell transplantation. However, at present, there are no clear guidelines for an orchestrated optimal treatment plan.
Assuntos
Benzoatos/efeitos adversos , Benzoatos/economia , Terapia por Quelação/ética , Doenças Hematológicas/tratamento farmacológico , Quelantes de Ferro/efeitos adversos , Quelantes de Ferro/economia , Triazóis/efeitos adversos , Triazóis/economia , Benzoatos/uso terapêutico , Terapia por Quelação/efeitos adversos , Deferasirox , Deferiprona , Desferroxamina/uso terapêutico , Custos de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Humanos , Quelantes de Ferro/uso terapêutico , Piridonas/uso terapêutico , Medição de Risco , Sideróforos/uso terapêutico , Triazóis/uso terapêuticoRESUMO
Although blood transfusions are important for patients with hemoglobinopathies, chronic transfusions inevitably lead to iron overload as humans cannot actively remove excess iron. The cumulative effects of iron overload lead to significant morbidity and mortality, if untreated. Desferrioxamine (DFO) is the reference-standard iron chelator whose safety and efficacy profile has been established through many years of clinical use. DFO side effects are acceptable and manageable however the prolonged subcutaneous infusion regimen of 5-7 days per week is very demanding and results in poor adherence to therapy. Deferiprone (Ferriprox, L1) is a bidentate molecule, orally administrable three-times/day, licensed in Europe and in other regions but in the USA and Canada, for the treatment of iron overload in patients for whom DFO therapy is contraindicated or inadequate. Preliminary evidences suggest that Deferiprone may be more effective than DFO in chelating cardiac iron. The side effects include gastrointestinal symptoms, liver dysfunction, joint pain, neutropenia and agranulocytosis. A weekly assessment of white blood cell counts is recommended because of the risk of agranulocytosis. Deferasirox is a new, convenient, once-daily oral iron chelator that has demonstrated in various clinical trials good efficacy and acceptable safety profile in adult and pediatric patients affected by transfusion-dependent thalassemia major and by different chronic anemias (SCD, BDA, MDS). The long half-life of Deferasirox (16-18 hours) provides sustained 24 hr iron chelation coverage. The efficacy and safety profile have been evaluated in more than 1000 patients in clinical trials allowing FDA registration. Patient satisfaction with Deferasirox was superior than with DFO therapy.
Assuntos
Terapia por Quelação/tendências , Hemoglobinopatias/tratamento farmacológico , Quelantes de Ferro/uso terapêutico , Terapia por Quelação/economia , Humanos , Quelantes de Ferro/economia , Cooperação do PacienteRESUMO
OBJECTIVES: Iron chelation treatment (ICT) in beta-thalassemia major (beta-TM) patients undergoing blood transfusions can cause low satisfaction, low compliance, with possible negative consequences on treatment success, patients' wellbeing, and costs. The purpose was to estimate the societal burden attributable to beta-TM in terms of direct and indirect costs, health-related quality-of-life (HRQoL), satisfaction and compliance with ICT in patients undergoing transfusions and ICT. RESEARCH DESIGN AND METHODS: The naturalistic, multicenter, longitudinal Italian-THAlassemia-Cost-&-Outcomes-Assessment (ITHACA) cost-of-illness study was conducted involving patients of any age, on ICT for at least 3 years, who were enrolled at 8 Italian Thalassemia Care Centers. Costs were estimated from the societal perspective, quantified with tariffs, prices, or net earnings valid in 2006. RESULTS: One-hundred and thirty-seven patients were enrolled (median age = 28.3, 3-48 years, 49.6% male) and retrospectively observed for a median of 11.6 months. Mean direct costs were euro1242/patient/month, 55.5% attributable to ICT, 33.2% attributable to transfusions. Relevant quantity and quality of productivity was lost. Both physical and mental components of HRQoL were compromised. Little difficulties remembering to take ICT and positive satisfaction with the perceived effectiveness of therapy were declared, but not good levels of satisfaction with acceptance, perception of side effects and burden of ICT. CONCLUSIONS: The management of beta-TM patients undergoing transfusions and ICT is efficacious, although costly, but overall benefits were not always perceived as optimal by patients. Efforts must be focused to improve patients' acceptance and satisfaction with their therapy; this would contribute to a better compliance and hence an increase in treatment effectiveness and patients' overall wellbeing, with expected improved allocation of human and economic resources.