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1.
Artigo em Inglês | MEDLINE | ID: mdl-32032239

RESUMO

Greece is a country of ~11 million people, where hemoglobinopathies are the most common genetic diseases. The reported data describe the clinical phenotype of cases with coinheritance of triplicated α-globin (anti-α3.7 kb) and ß-globin gene mutations in Northern Greece, that were referred within the last 10 years, in The Adult Thalassemia Unit of "Hippokration" Hospital, Thessaloniki, Northern Greece. The description of specific genotypes of the ß-globin gene mutations in coinheritance with the triplicated α-globin gene (anti-α3.7 kb) and correlation with the hematological and clinical data in adulthood may be useful in the evaluation of pediatric patients' prognosis and in genetic counseling of couples at risk.

2.
Hemoglobin ; 43(1): 27-33, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31039620

RESUMO

Hemoglobinopathies exhibit a remarkable phenotypic diversity in terms of disease severity, while individual genetic background plays a key role in differential response to drug treatment. In the last decade, genomic variants in genes located within, as well as outside the human ß-globin cluster have been shown to be significantly associated with Hb F increase, in relation to hydroxyurea (HU) therapy in patients with these diseases. Here, we aim to determine the effect of genomic variants located in genes, such as MAP3K5, ASS1, NOS2A, TOX, PDE7B, NOS1, FLT1 and ARG2, previously shown to modulate fetal hemoglobin (Hb F) levels in patients with ß type hemoglobinopathies and reflecting disease severity and response to HU therapy in an independent cohort of Greek patients with these diseases. We recruited and genotyped 45 ß-thalassemia patients (ß-thal), either transfusion-dependent (TDT) or non transfusion-dependent (NTDT), 42 Hb S (HBB: c.20A>T)-ß-thal compound heterozygotes, who were treated with HU, as well as 53 healthy individuals, all of Hellenic origin. Our study showed that genomic variants of the MAP3K5, NOS2A and ARG2 gene are associated with HU therapy efficacy in Hb S-ß-thal compound heterozygotes. We have also shown that FLT1 and ARG2 genomic variants are associated with the mild phenotype of NTDT patients. Our findings provide evidence that MAP3K5, NOS2A, ARG2 and FLT1 genomic variants could be considered as genomic biomarkers to predict HU therapy efficacy in Hb S-ß-thal compound heterozygotes and also to describe disease severity in patients with ß type hemoglobinopathies.


Assuntos
Biomarcadores , Hemoglobina Fetal , Hidroxiureia/uso terapêutico , Globinas beta/genética , Talassemia beta/tratamento farmacológico , Talassemia beta/genética , Alelos , Feminino , Genômica/métodos , Genótipo , Humanos , Masculino , Mutação , Fenótipo , Índice de Gravidade de Doença , Resultado do Tratamento , Talassemia beta/sangue , Talassemia beta/diagnóstico
3.
Hematology ; 24(1): 426-438, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30947625

RESUMO

OBJECTIVES: Beta-thalassemias are a group of recessively autosomal inherited disorders of hemoglobin synthesis, which, due to mutations of the beta-globin gene, lead to various degrees of defective beta-chain production, an imbalance in alpha/beta-globin chain synthesis, ineffective erythropoiesis, and anemia. Improved survival in thalassemic patients has led to the emergence of previously unrecognized complications, such as renal disease. METHODS: A comprehensive literature review through PubMed was undertaken to summarize the published evidence on the epidemiology and pathophysiology of renal disease in thalassemia. Literature sources published in English since 1990 were searched, using the terms beta-thalassemia, renal disease. RESULTS: Renal disease is considered to be the 4th cause of morbidity among patients with transfusion dependent thalassemia. Chronic anemia, hypoxia and iron overload are the main mechanisms implicated in development of renal injury, whereas several studies also suggested a contributive role of iron chelators. DISCUSSION AND CONCLUSION: Kidney disease may develop through progressive renal tubular and glomerular damage; thus, its early recognition is important in order to prevent and/or reverse deterioration. This review will provide an insight on the involved mechanisms implicated in kidney disease in thalassemic patients and will discuss the updates on diagnosis and prevention of renal complications in thalassemia.


Assuntos
Hipóxia , Sobrecarga de Ferro , Nefropatias , Talassemia beta , Feminino , Humanos , Hipóxia/complicações , Hipóxia/metabolismo , Hipóxia/mortalidade , Hipóxia/terapia , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/mortalidade , Sobrecarga de Ferro/terapia , Nefropatias/etiologia , Nefropatias/metabolismo , Nefropatias/mortalidade , Nefropatias/terapia , Masculino , Talassemia beta/complicações , Talassemia beta/metabolismo , Talassemia beta/mortalidade , Talassemia beta/terapia
4.
Ann Hematol ; 98(1): 55-66, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30196444

RESUMO

National registries constitute an invaluable source of information and contribute to the improvement of hemoglobinopathy management. Herein, we present the second updated report of the National Registry for Haemoglobinopathies in Greece (NRHG) and critically discuss the time trends in demographics, affected births, and causes of mortality. Thirty-eight Greek hemoglobinopathy units reported data from diagnosis to the last follow-up or death by retrospectively completing an electronic form. Four thousand thirty-two patients were eligible for inclusion; more than half of them had thalassaemia major. Compared to the previous report, a reduction in the total number of all hemoglobinopathies except for hemoglobinopathy "Η" was evident. The total number of affected births was also reduced; most of them were attributable to diagnostic errors and lack of awareness. Importantly, data on iron overload are reported for the first time; although most patients had low or moderate liver iron concentration (LIC) values, a non-negligible proportion of patients had high LIC. The burden due to heart iron overload was less prominent. Cardiac- and liver-related complications are the major causes of morbidity and mortality. From 2000 to 2015, a decrease in heart-related deaths along with an increase in liver-associated fatalities was observed. The Hellenic Prevention Program along with advances in chelation regimens and iron status monitoring have resulted in improved patient outcomes. The NRHG gives insight into the effectiveness of prevention programs, the therapeutic management of hemoglobinopathies and associated outcomes. NRHG may contribute to the formulation of a roadmap for hemoglobinopathies in Europe and promote the implementation of effective public health policies.


Assuntos
Hemoglobinopatias/epidemiologia , Sistema de Registros , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Grécia/epidemiologia , Cardiopatias/sangue , Cardiopatias/epidemiologia , Cardiopatias/etiologia , Hemoglobinopatias/complicações , Hemoglobinopatias/metabolismo , Humanos , Lactente , Ferro/metabolismo , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/epidemiologia , Sobrecarga de Ferro/etiologia , Fígado/metabolismo , Hepatopatias/sangue , Hepatopatias/epidemiologia , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade
5.
Mol Pharm ; 15(12): 5665-5677, 2018 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-30375878

RESUMO

Protein replacement therapy (PRT) has been applied to treat severe monogenetic/metabolic disorders characterized by a protein deficiency. In disorders where an intracellular protein is missing, PRT is not easily feasible due to the inability of proteins to cross the cell membrane. Instead, gene therapy has been applied, although still with limited success. ß-Thalassemias are severe congenital hemoglobinopathies, characterized by deficiency or reduced production of the adult ß-globin chain. The resulting imbalance of α-/ß-globin chains of adult hemoglobin (α2ß2) leads to precipitation of unpaired α-globin chains and, eventually, to defective erythropoiesis. Since protein transduction domain (PTD) technology has emerged as a promising therapeutic approach, we produced a human recombinant ß-globin chain in fusion with the TAT peptide and successfully transduced it into human proerythroid K-562 cells, deficient in mature ß-globin chain. Notably, the produced human recombinant ß-globin chain without the TAT peptide, used as internal negative control, failed to be transduced into K-562 cells under similar conditions. In silico studies complemented by SDS-PAGE, Western blotting, co-immunoprecipitation and LC-MS/MS analysis indicated that the transduced recombinant fusion TAT-ß-globin protein interacts with the endogenous native α-like globins to form hemoglobin α2ß2-like tetramers to a limited extent. Our findings provide evidence that recombinant TAT-ß-globin is transmissible into proerythroid K-562 cells and can be potentially considered as an alternative protein therapeutic approach for ß-thalassemias.


Assuntos
Proteínas Recombinantes de Fusão/uso terapêutico , Globinas beta/uso terapêutico , Talassemia beta/terapia , Produtos do Gene tat do Vírus da Imunodeficiência Humana/uso terapêutico , Terapia Biológica/métodos , Linhagem Celular , Humanos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/isolamento & purificação , Transdução Genética/métodos , alfa-Globinas/metabolismo , Globinas beta/genética , Globinas beta/isolamento & purificação , Talassemia beta/genética , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética , Produtos do Gene tat do Vírus da Imunodeficiência Humana/isolamento & purificação
6.
Hum Genomics ; 12(1): 45, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30285874

RESUMO

BACKGROUND: We aimed to clarify the emerging epigenetic landscape in a group of genes classified as "modifier genes" of the ß-type globin genes (HBB cluster), known to operate in trans to accomplish the two natural developmental switches in globin expression, from embryonic to fetal during the first trimester of conception and from fetal to adult around the time of birth. The epigenetic alterations were determined in adult sickle cell anemia (SCA) homozygotes and SCA/ß-thalassemia compound heterozygotes of Greek origin, who are under hydroxyurea (HU) treatment. Patients were distinguished in HU responders and HU non-responders (those not benefited from the HU) and both, and in vivo and in vitro approaches were implemented. RESULTS: We examined the CpG islands' DNA methylation profile of BCL11A, KLF1, MYB, MAP3K5, SIN3A, ZBTB7A, and GATA2, along with γ-globin and LRF/ZBTB7A expression levels. In vitro treatment of hematopoietic stem cells (HSCs) with HU induced a significant DNA hypomethylation pattern in ZBTB7A (p*, 0.04) and GATA2 (p*, 0.03) CpGs exclusively in the HU non-responders. Also, this group of patients exhibited significantly elevated baseline methylation patterns in ZBTB7A, before the HU treatment, compared to HU responders (p*, 0.019) and to control group of healthy individuals (p*, 0.021), which resembles a potential epigenetic barrier for the γ-globin expression. γ-Globin expression in vitro matched with detected HbF levels during patients' monitoring tests (in vivo) under HU treatment, implying a good reproducibility of the in vitro HU epigenetic effect. LRF/ZBTB7A expression was elevated only in the HU non-responders under the influence of HU. CONCLUSIONS: This is one of the very first pharmacoepigenomic studies indicating that the hypomethylation of ZBTB7A during HU treatment enhances the LRF expression, which by its turn suppresses the HbF resumption in the HU non-responders. Its role as an epigenetic regulator of hemoglobin switching is also supported by the wide distribution of ZBTB7A-binding sites within the 5' CpG sequences of all studied human HBB cluster "modifier genes." Also, the baseline methylation level of selective CpGs in ZBTB7A and GATA2 could be an indicator of the negative HU response among the ß-type hemoglobinopathy patients.


Assuntos
Anemia Falciforme/genética , Metilação de DNA/genética , Proteínas de Ligação a DNA/genética , Hidroxiureia/administração & dosagem , Fatores de Transcrição/genética , Talassemia beta/genética , Anemia Falciforme/sangue , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/patologia , Proteínas de Transporte/genética , Metilação de DNA/efeitos dos fármacos , Feminino , Fator de Transcrição GATA2/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Heterozigoto , Humanos , Hidroxiureia/efeitos adversos , Fatores de Transcrição Kruppel-Like/genética , MAP Quinase Quinase Quinase 5/genética , Masculino , Proteínas Nucleares/genética , Proteínas Repressoras/genética , Globinas beta/genética , Talassemia beta/sangue , Talassemia beta/tratamento farmacológico , Talassemia beta/patologia
8.
Hemoglobin ; 42(3): 194-195, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-30205726

RESUMO

The rare point mutation Cap +1570 (T>C) (HBB: c*96T>C) has been reported in families of Czech, Greek, Turkish and Italian origin. The mutation contributes to a reduction of the ß-globin chain synthesis, and in heterozygous carriers, it causes a silent phenotype, while in compound heterozygosity with severe ß-thalassemia (ß-thal) mutations, it leads to a non transfusion dependent ß-thal intermedia (ß-TI) state. We report a case of compound heterozygosity for codon 39 (C>T) (HBB: c.118C>T) and Cap +1570, in addition to the presence of αααanti-3.7/αα.


Assuntos
Heterozigoto , Mutação , Globinas beta/genética , Talassemia beta/genética , Frequência do Gene , Grécia , Humanos , Mutação Silenciosa , alfa-Globinas/genética
9.
Metabolism ; 87: 18-24, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29936174

RESUMO

Both Helicobacter pylori infection and metabolic syndrome present significant global public health burdens. Metabolic syndrome is closely related to insulin resistance, the major underlying mechanism responsible for metabolic abnormalities, and Helicobacter pylori infection has been proposed to be a contributing factor. There is growing evidence for a potential association between Helicobacter pylori infection and insulin resistance, metabolic syndrome and related morbidity, including abdominal obesity, type 2 diabetes mellitus, dyslipidemia, hypertension, all of which increase mortality related to cardio-cerebrovascular disease, neurodegenerative disorders, nonalcoholic fatty liver disease and malignancies. More specifically, insulin resistance, metabolic syndrome and hyperinsulinemia have been associated with upper and lower gastrointestinal tract oncogenesis. Apart from cardio-cerebrovascular, degenerative diseases and nonalcoholic fatty liver disease, a number of studies claim that Helicobacter pylori infection is implicated in metabolic syndrome-related Barrett's esophagus and esophageal adenocarcinoma development, gastric and duodenal ulcers and gastric oncogenesis as well as lower gastrointestinal tract oncogenesis. This review summarizes evidence on the potential impact of Helicobacter pylori-related metabolic syndrome on gastroesophageal reflux disease-Barrett's esophagus-esophageal adenocarcinoma, gastric atrophy-intestinal metaplasia-dysplasia-gastric cancer and colorectal adenoma-dysplasia-colorectal cancer sequences. Helicobacter pylori eradication might inhibit these oncogenic processes, and thus further studies are warranted.


Assuntos
Carcinogênese , Neoplasias Gastrointestinais/etiologia , Infecções por Helicobacter/metabolismo , Helicobacter pylori , Síndrome Metabólica/metabolismo , Animais , Gastroenteropatias/etiologia , Gastroenteropatias/microbiologia , Neoplasias Gastrointestinais/microbiologia , Infecções por Helicobacter/complicações , Humanos , Síndrome Metabólica/complicações
10.
J Obstet Gynaecol ; 38(4): 443-447, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29057687

RESUMO

The management of iron deficiency anaemia (IDA) consists of oral or intravenous administration of iron supplements. The aim of this narrative review is to summarise information regarding the treatment of IDA in women who have postpartum anaemia or uterine bleeding with intravenous (IV) or oral iron supplements. Fourteen randomised control studies comparing IV to oral iron treatment for IDA in 2913 women with uterine bleeding or postpartum haemorrhage are included. All reviewed studies suggest that IV iron administration is important in treating the IDA in such women and in improving their physical performance and quality of life. Comparisons among intravenous iron supplements show advantages of ferric carboxymaltose over others in time of reaching desired haemoglobin and ferritin values and in adverse reactions. Despite the limitation that the above evidence emerges from not systematically collected data, our review highlights that new forms of IV iron supplements seem safe and efficient in treating IDA.


Assuntos
Anemia Ferropriva/tratamento farmacológico , Hematínicos/administração & dosagem , Compostos de Ferro/administração & dosagem , Transtornos Puerperais/tratamento farmacológico , Administração Intravenosa , Administração Oral , Feminino , Hematínicos/efeitos adversos , Humanos , Compostos de Ferro/efeitos adversos , Gravidez , Resultado do Tratamento
12.
Balkan Med J ; 35(1): 112-115, 2018 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-28903884

RESUMO

BACKGROUND: Acquired coagulation factor inhibitors are antibodies that either inhibit activity or increase the clearance of a clotting factor and lead to an increased risk of bleeding. Most of the time, the disorder is attributed to factor VIII inhibition (acquired haemophilia A); however, other coagulation factors could also be implicated. CASE REPORT: Herein, we report an interesting case of a patient who underwent coronary artery bypass grafting and received antibiotic treatment after surgery with third generation cephalosporin. A month later, he presented with extreme bleeding diathesis and cerebral haemorrhage. Following a thorough clinical and laboratory investigation, an acquired factor V inhibitor was diagnosed. The patient received treatment with corticosteroids, intravenous immunoglobulins, anti-CD20 monoclonal antibodies (rituximab), cyclophosphamide and recombinant factor VIIa. Finally, despite the poor initial prognosis, the patient managed to achieve a full recovery. CONCLUSION: As there are no clear guidelines on acquired coagulation inhibitor treatment, reports of such cases could offer insight for future therapy choices. The case was unique because the treatment regimen included a combination of multiple therapeutic agents including rituximab.


Assuntos
Hemorragia Cerebral/etiologia , Ciclofosfamida/uso terapêutico , Fator V/antagonistas & inibidores , Rituximab/uso terapêutico , Idoso , Hemofilia A , Heparina de Baixo Peso Molecular , Humanos , Masculino , Resultado do Tratamento
13.
Hemoglobin ; 42(5-6): 339-341, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30626228

RESUMO

Delayed hemolytic transfusion reaction (DHTR) is a life-threatening complication in patients with sickle cell disease, characterized by difficulties in diagnosis and management. Certain reports have suggested successful salvage treatment with the terminal complement inhibitor, eculizumab. We here report evidence of complement activation and successful complement inhibition with one dose of eculizumab in an adult sickle cell disease patient presenting DHTR with hyperhemolysis. A 21-year old female sickle cell disease patient [Hb S (HBB: c.20A>T)/ß-thalassemia (ß-thal)] presented at our Adult Thalassaemia Unit, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece, with headaches, perioral numbness and pain in both antibrachia. The patient was admitted with the diagnosis of vaso-occlussive crisis (VOC) and treated symptomatically. On her third day of admission, due to hemoglobin (Hb) value of 6.9 g/dL with increase in reticulocytes, the patient was transfused with one unit of compatible leukodepleted red blood cells (RBC). The following day, hemolytic parameters increased, although Coombs, panel antibodies and screening tests were negative. Five days later, she again received a unit of RBCs, resulting in another increase of hemolytic parameters. During the following 2 days, there was a dramatic decrease of Hb levels to 5.4 g/dL with reticulocytes at 6.0%, negative Coombs testing and negative alloantibodies. Based on these findings, we recognized the syndrome of DHTR with hyperhemolysis. Given the lack of immediate access to other treatment, we administered intravenous rituximab, immunoglobulins and corticosteroids. As there was no response, one dose of eculizumab (900 mg) was then administered with ciprofloxacin as prophylaxis. The patient remains well 6 months post treatment.


Assuntos
Anemia Falciforme/complicações , Anticorpos Monoclonais Humanizados/administração & dosagem , Reação Transfusional/etiologia , Anemia Falciforme/terapia , Antibioticoprofilaxia , Anticorpos Monoclonais Humanizados/uso terapêutico , Ciprofloxacino , Feminino , Hemólise , Humanos , Terapia de Salvação , Resultado do Tratamento , Adulto Jovem
15.
Surg Innov ; 24(6): 543-551, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28877644

RESUMO

BACKGROUND: To investigate the early and late antiadhesive effect and any changes of fibrin matrix regulation enzymes on rat peritoneum, after local administration of bevacizumab. METHODS: Rats were subjected to cecal abrasion. Bevacizumab (5 mg/kg) against placebo was given intraperitoneally. On the 2nd, 14th, and 28th postoperative days adhesions were scored, and tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-9 (MMP-9), degree of fibrosis, and angiogenesis were measured in abrased cecum and in intact parietal peritoneum. RESULTS: Bevacizumab significantly reduced adhesions up to 15% on the 2nd, 52.5% on the 14th, and 55% on the 28th postoperative day, and significantly increased tPA concentrations in peritoneum. PAI-1 was decreased, and a significantly higher tPA/PAI-1 ratio along with an increase of MMP-9 was measured at all time points. Fibrosis and angiogenesis were significantly lower on the 14th and 28th postoperative days. CONCLUSIONS: Local bevacizumab administration has a strong early and late antiadhesive action on rat peritoneum, mediated by changes in the tPA/PAI-1 and MMP balance in favor of fibrinolysis up to 28 days after operations.


Assuntos
Inibidores da Angiogênese/farmacologia , Bevacizumab/farmacologia , Ceco/efeitos dos fármacos , Fibrinólise/efeitos dos fármacos , Peritônio/efeitos dos fármacos , Aderências Teciduais/prevenção & controle , Animais , Ceco/patologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Peritônio/patologia , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Ratos , Ratos Wistar , Ativador de Plasminogênio Tecidual/metabolismo
16.
Ann Hematol ; 96(11): 1937-1944, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28884221

RESUMO

The aim of our study was to evaluate the Greek version of the transfusion-dependent quality of life (TranQol) questionnaire and report our experience of using this novel disease-specific quality of life (QoL) measure in patients with transfusion-dependent thalassemia (TDT). The TranQol and SF-36v2 questionnaires were administered to 94 adult TDT patients with a mean age of 32.1 years (SD = 7, range = 19-58), recruited from the Adult Thalassemia Unit of Hippokration General Hospital of Thessaloniki, Greece. The TranQol was evaluated in terms of construct validity, reliability, and responsiveness. There was a moderately strong correlation between the TranQol summary and both the SF-36v2 physical and mental component summaries (r = 0.4, p < 0.001 and r = 0.5, p < 0.001, respectively). There was also a moderately strong correlation between the physical health scale of TranQol and the relevant SF-36v2 scales, including physical functioning (r = 0.4, p < 0.001), role-physical (r = 0.6, p < 0.001), and bodily pain (r = 0.5, p < 0.001). TranQol also exhibited good internal consistency (Cronbach's alpha coefficient = 0.9) and excellent test-retest reliability (intra-class correlation coefficient = 0.9). The subgroup of patients that reported a better QoL 1 week after transfusion also demonstrated a significant improvement in their TranQol score. These are the first data regarding the administration of the Greek TranQol in a single thalassemia unit. The psychometric properties of the Greek TranQol confirmed it is a valid, reliable, and responsive to change questionnaire, which can be incorporated into future clinical trials.


Assuntos
Transfusão de Sangue/psicologia , Qualidade de Vida/psicologia , Inquéritos e Questionários/normas , Talassemia beta/psicologia , Adulto , Estudos Transversais , Feminino , Grécia/epidemiologia , Humanos , Quelantes de Ferro/uso terapêutico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Talassemia beta/diagnóstico , Talassemia beta/terapia
18.
Hemoglobin ; 41(3): 223-224, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28950780

RESUMO

The use of rivaroxaban in patients with hemoglobinopathies and thrombotic events has not been studied extensively. Here we present eight cases of such patients, five receiving rivaroxaban for stroke and systemic embolism prevention due to non-valvular atrial fibrillation and three for deep vein thrombosis treatment. The follow-up period ranged from 6 to 34 months. During this period none of the patients experienced any thrombotic or bleeding event.There were no other adverse events reported. Further studies with larger numbers of patients with hemoglobinopathies are needed to determine the use of rivaroxaban and ensure its safety in this patient setting.


Assuntos
Inibidores do Fator Xa/uso terapêutico , Hemoglobinopatias/complicações , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Adulto , Idoso , Anemia Falciforme/complicações , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Resultado do Tratamento , Talassemia beta/complicações
20.
Br J Haematol ; 178(1): 130-136, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28439915

RESUMO

Interferon-based regimens for chronic hepatitis C (CHC) were often deferred in patients with ß-thalasaemia major (ß-TM) due to poor efficacy and tolerance. Current guidelines recommend direct-acting antivirals (DAAs) for these patients. The aim of this study was to assess the safety and efficacy of DAAs in patients with ß-TM and advanced liver disease due to CHC. Patients were recruited from eight liver units in Greece. The stage of liver disease was assessed using transient elastography and/or liver histology. Five regimens were used: sofosbuvir (SOF) + ribavirin (RBV); SOF + simeprevir ± RBV; SOF + daclatasvir ± RBV; ledipasvir/SOF ± RBV and ombitasvir/paritaprevir-ritonavir + dasabuvir ± RBV. Sixty-one patients (median age 43 years) were included. The majority of patients was previously treated for hepatitis C (75%) and had cirrhosis (79%). Viral genotype distribution was: G1a: n = 10 (16%); G1b: n = 22 (36%); G2: n = 2 (3%); G3: n = 14 (23%); G4: n = 13 (22%). The predominant chelation therapy was a combination of deferoxamine and deferiprone (35%). Overall sustained virological response rates were 90%. All treatment regimens were well tolerated and no major adverse events or drug-drug interactions were observed. Approximately half of the patients who received RBV (7/16, 44%) had increased needs for blood transfusion. Treatment of CHC with DAAs in patients with ß-TM and advanced liver disease was highly effective and safe.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Talassemia beta/complicações , Adulto , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Imidazóis/efeitos adversos , Imidazóis/uso terapêutico , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Ribavirina/efeitos adversos , Ribavirina/uso terapêutico , Índice de Gravidade de Doença , Simeprevir/efeitos adversos , Simeprevir/uso terapêutico , Sofosbuvir/efeitos adversos , Sofosbuvir/uso terapêutico
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