Thalassemia Reports

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Open AccessAbstract

Abstract Book

by F. Pane and A. Maggio

Thalass. Rep. 2014, 4(2), 4725; https://doi.org/10.4081/thal.2014.4725 - 29 Sep 2014

Viewed by 289

Relapsed/refractory AML patients have a poor prognosis, with CR rates of 1–30%, unless allogeneic hematopoietic stem cell transplantation (HSCT) is an available option [...] Full article

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Open AccessObituary

Remembrance for Prof. Antonio Cao and Prof. Renzo Galanello

by Paolo Moi

Thalass. Rep. 2014, 4(2), 3223; https://doi.org/10.4081/thal.2014.3223 - 29 Sep 2014

Viewed by 281

Abstract

In less than one year Antonio Cao (Cagliari, 4 May 1929–Cagliari, 21 June 2012) and Renzo Galanello (Parrano, 21 July 1948–Cagliari, 13 May 2013), two amongst the greatest scientists in the fields of Pediatrics, Hematology and Thalassemia, have passed away. Their deaths are [...] Read more.

In less than one year Antonio Cao (Cagliari, 4 May 1929–Cagliari, 21 June 2012) and Renzo Galanello (Parrano, 21 July 1948–Cagliari, 13 May 2013), two amongst the greatest scientists in the fields of Pediatrics, Hematology and Thalassemia, have passed away. Their deaths are an enormous loss for all of us in the Hospital for Microcitemias in Cagliari, but also for the whole Italian and International scientific community, who recognized and admired their leadership. During the funeral ceremonies held in our Hospital where both spent the greatest part of their lives, the most touching words were those pronounced by the patients who were cured by and benefited of the scrupulous medical care of our colleagues for decades from their infancy to adulthood [...] Full article

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Open AccessReview

Development and Recent Progresses of Gene Therapy for β-Thalassemia

by Santina Acuto, Elena Baiamonte, Rosalia Di Stefano, Barbara Spina, Rita Barone and Aurelio Maggio

Thalass. Rep. 2014, 4(2), 2925; https://doi.org/10.4081/thal.2014.2925 - 29 Sep 2014

Viewed by 325

Abstract

β-thalassemias are among the most common inherited monogenic disorders worldwide due to mutations in the β-globin gene that reduce or abolish the production of the β-globin chain resulting in transfusion-dependent chronic anemia. Currently, the only curative treatment is allogeneic hematopoietic stem cells (HSCs) [...] Read more.

β-thalassemias are among the most common inherited monogenic disorders worldwide due to mutations in the β-globin gene that reduce or abolish the production of the β-globin chain resulting in transfusion-dependent chronic anemia. Currently, the only curative treatment is allogeneic hematopoietic stem cells (HSCs) transplantation, but this option is limited by the a vailability of HLA-matched donor. Gene therapy, based on autologous transplantation of genetically corrected HSCs, holds the promise to treat patients lacking a compati ble bone marrow donor. I nit ial attempts of gene transfer have been unsuccessful due to limitations of available vectors to stably transfer a globin gene in HSCs and reach high and regulated expression in the erythroid progeny. With the advent of lentiviral vectors (LVs), based on human immunodeficiency virus, many of the initial limitations have been overcome. Since 2000 when Sadelain and co-workers first demonstrated successful globin gene transfer in murine thalassemia models with improvement of the phenotype using a recombinant β globin/LV, several other groups have developed different vectors encoding either β, γ or mutated globin genes and confirmed these results in both murine models and erythroid progeny derived from patient’s HSCs. In light of these encouraging results, research has recently moved into clinical trials that are ongoing or soon to begin. One participant in an ongoing gene transfer trial for β-thalassemia has achieved clinical benefit with elimination of his transfusi on re quirement. Here , dev elopmen t and recent progress of gene therapy for β-thalassemia is reviewed. Full article

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Open AccessArticle

Role of Iron Metabolism Genetic Determinants in Response to Chelation Therapy in a Cohort of β-Thalassemia and Sickle Cell Syndromes Italian Patients

by Maria Concetta Renda, Disma Renda, Angela Piazza, Giuseppina Calvaruso, Emanuela Fecarotta, Antonino Giangreco and Aurelio Maggio

Thalass. Rep. 2014, 4(2), 2729; https://doi.org/10.4081/thal.2014.2729 - 29 Sep 2014

Cited by 1 | Viewed by 469

Abstract

In patients with β-thalassemia and sickle cell syndromes there is an important secondary iron overload due to regular blood transfusions and increased duodenal iron absorption. As in genetic hemochromatosis, also the secondary iron storage leads to tissue injury that involves all the major [...] Read more.

In patients with β-thalassemia and sickle cell syndromes there is an important secondary iron overload due to regular blood transfusions and increased duodenal iron absorption. As in genetic hemochromatosis, also the secondary iron storage leads to tissue injury that involves all the major organs: liver, heart, kidney, endocrine glands. At present, in patients with β-thalassemia and sickle cell syndrome, iron chelation therapy is widely used for the treatment of secondary hemochromatosis, to limit the toxic effects of iron overload. In order to maintain the correct homeostasis, several genes are involved in the metabolic pathways of iron, including HFE, FPN (ferroportin) and TF (transferrin). In this study we analyzed the genes HFE, FPN and TF, to assess their possible effects on response to therapy with deferasirox and deferiprone, either as monotherapy or in combination therapy in a cohort of patients with β-thalassemia and sickle cell syndromes. Full article

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Open AccessReview

Recent Developments Centered on Orally Active Iron Chelators

by Robert Hider

Thalass. Rep. 2014, 4(2), 2261; https://doi.org/10.4081/thal.2014.2261 - 29 Sep 2014

Cited by 11 | Viewed by 450

Abstract

Over the past twenty years there has been a growing interest in the orally active iron chelators, deferiprone and deferasirox, both have been extensively studied. The ability of these compounds to mobilize iron from the heart and endocrine tissue has presented the clinician [...] Read more.

Over the past twenty years there has been a growing interest in the orally active iron chelators, deferiprone and deferasirox, both have been extensively studied. The ability of these compounds to mobilize iron from the heart and endocrine tissue has presented the clinician with some advantages over desferrioxamine, the first therapeutic iron chelator. Other orally active iron chelators are currently under development. The critical features necessary for the design of therapeutically useful orally active iron chelators are presented in this review, together with recent studies devoted to the design of such chelators. This newly emerging range of iron chelators will enable clinicians to apply iron chelation methodology to other disease states and to begin to design personalized chelation regimes. Full article

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Open AccessReview

Prenatal Diagnosis of Hemoglobinopathies: From Fetoscopy to Coelocentesis

by Gianfranca Damiani, Margherita Vinciguerra, Cristina Jakil, Monica Cannata, Filippo Cassarà, Francesco Picciotto, Giovanna Schillaci, Valentina Cigna, Disma Renda, Aldo Volpes, Francesca Sammartano, Samuela Milone, Adolfo Allegra, Cristina Passarello, Filippo Leto and Antonino Giambona

Thalass. Rep. 2014, 4(2), 2200; https://doi.org/10.4081/thal.2014.2200 - 29 Sep 2014

Viewed by 297

Abstract

Prenatal diagnosis of hemoglobinopathies involves the study of fetal material from blood, amniocytes, trophoblast coelomatic cells and fetal DNA in maternal circulation. Its first application dates back to the 70s and it involves globin chain synthesis analysis on fetal blood. In the 1980s [...] Read more.

Prenatal diagnosis of hemoglobinopathies involves the study of fetal material from blood, amniocytes, trophoblast coelomatic cells and fetal DNA in maternal circulation. Its first application dates back to the 70s and it involves globin chain synthesis analysis on fetal blood. In the 1980s molecular analysis was introduced as well as amniocentesis and chorionic villi sampling under high-resolution ultrasound imaging. The application of direct sequencing and polymerase chain reactionbased methodologies improved the DNA analysis procedures and reduced the sampling age for invasive prenatal diagnosis from 18 to 16–11 weeks allowing fetal genotyping within the first trimester of pregnancy. In the last years, fetal material obtained at 7–8 weeks of gestation by coelocentesis and isolation of fetal cells has provided new platforms on which to develop diagnostic capabilities while non-invasive technologies using fetal DNA in maternal circulation are starting to develop. Full article

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Open AccessReview

Reactivation of Fetal Hemoglobin in Thalassemia and Sickle Cell Disease

by Sandro Eridani, Francesca Avemaria and Andrea Mosca

Thalass. Rep. 2014, 4(2), 2196; https://doi.org/10.4081/thal.2014.2196 - 29 Sep 2014

Cited by 1 | Viewed by 333

Abstract

Considerable attention has been recently devoted to mechanisms involved in the perinatal hemoglobin switch, as it was long ago established that the survival of fetal hemoglobin (HbF) production in significant amount can reduce the severity of the clinical course in severe disorders like [...] Read more.

Considerable attention has been recently devoted to mechanisms involved in the perinatal hemoglobin switch, as it was long ago established that the survival of fetal hemoglobin (HbF) production in significant amount can reduce the severity of the clinical course in severe disorders like β-thalassemia and sickle cell disease (SCD). For instance, when β-thalassemia is associated with hereditary persistence of fetal hemoglobin (HPFH) the disease takes a mild course, labeled as thalassemia intermedia. The same clinical amelioration occurs for the association between HPFH and SCD. As for the mechanism of this effect, some information has been obtained from the study of natural mutations at the human β-globin locus in patients with increased HbF, like the Corfu thalassemia mutations. Important evidence came from the discovery that drugs capable of improving the clinical picture of SCD, like decitabine ad hydroxycarbamide, are acting through the reactivation, to some extent, of HbF synthesis. The study of the mechanism of action of these compounds was followed by the identification of some genetic determinants, which promote this event. In particular, among a few genetic factors involved in this process, the most relevant appears the BCL11A gene, which is now credited to be able to silence γ-globin genes in the perinatal period by interaction with several erythroid-specific transcription factors and is actually considered as a barrier to HbF reactivation by known HbF inducing agents. Epigenetics is also a player in the process, mainly through DNA demethylation. This is certified by the recent demonstration that hypomethylating agents such as 5-azacytidine and decitabine, the first compounds used for HbF induction by pharmacology, act as irreversible inhibitors of demethyltransferase enzymes. Great interest has also been raised by the finding that several micro-RNAs, which act as negative regulators of gene expression, have been implicated in the progression of globin gene expression and, particularly, in the reactivation of γ-globin gene expression associated with increased HbF synthesis. Probably, this reactivation is achieved by post-transcriptional inhibition of BCL11A expression. Finally, attention is presently focused on a recently discovered BCL11A enhancer, essential for erythroid expression of BCL11A, which might become a therapeutic target for genome engineering in the β-hemoglobinopathies as its disruption affects only the erythropoietic lineage, without hurting other cell or tissue compartments. Full article

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Open AccessArticle

Development of Plasmids for Quantitative Detection of Integrated Lentiviral Vectors and Evaluation of Culture Time to Perform Vector Titer by Real-Time Quantitative Polymerase Chain Reaction Assay

by Elena Baiamonte, Mariella Bagliesi, Valentina Motta, Barbara Spina and Alice Pecoraro

Thalass. Rep. 2014, 4(2), 2189; https://doi.org/10.4081/thal.2014.2189 - 29 Sep 2014

Cited by 1 | Viewed by 349

Abstract

The accurate assessment of provirus copy number per cell (VCN/cell) is a fundamental issue in transgenesis as well as in gene therapy studies based on stably integrated vectors. To this end, real-time quantitative polymerase chain reaction (qPCR) is a powerful method but it [...] Read more.

The accurate assessment of provirus copy number per cell (VCN/cell) is a fundamental issue in transgenesis as well as in gene therapy studies based on stably integrated vectors. To this end, real-time quantitative polymerase chain reaction (qPCR) is a powerful method but it is sensible to differences in quality or concentration of the two-plasmid preparations used for the construction of the standard curves. In order to minimize technical errors we included genome specific sequences (mouse or human) and vector specific sequences in the same plasmid. We evaluated the specificity and sensitivity of these bivalent plasmids by qPCR analysis on mouse and human genomic DNA containing a known number of a reporter lentiviral vector and we found that the system is reliable to measure up to 0.1 VCN/cell. Here we have applied this assay to measure vector titer of virus stock preparations and to determine the optimal cell passages at which viral titration effectively reflects the number of integrated vectors. Full article

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Open AccessArticle

Reference Intervals for Acetylated Fetal Hemoglobin in Healthy Newborns

by Renata Paleari, Irene Mutta, Gianluca Musolino, Alessandro Salvatoni, Massimo Agosti, Gaia Francescato and Andrea Mosca

Thalass. Rep. 2014, 4(2), 2120; https://doi.org/10.4081/thal.2014.2120 - 29 Sep 2014

Viewed by 372

Abstract

The acetylated fetal hemoglobin (AcHbF) derives from an enzyme-mediated post-translational modification occurring on the N-terminal glycine residues of γ-chains. At present, no established data are available on reference intervals for AcHbF in newborns. A total of 92 healthy infants, with gestational age between [...] Read more.

The acetylated fetal hemoglobin (AcHbF) derives from an enzyme-mediated post-translational modification occurring on the N-terminal glycine residues of γ-chains. At present, no established data are available on reference intervals for AcHbF in newborns. A total of 92 healthy infants, with gestational age between 37 and 41 weeks were selected for the establishment of AcHbF reference intervals. Blood samples were collected by heel pricking, when collecting routine neonatal screening, and the hemoglobin pattern was analyzed by high-performance liquid chromatography. AcHbF results were then normalized for HbF content in order to account for differences in hemoglobin switch. No difference was found in AcHbF values between genders (P = 0.858). AcHbF results were as follow: 12.8 ± 0.8% (mean±standard deviation), reference interval: 11.3–14.3%. This finding could facilitate further studies aimed to assess the possible use of AcHbF, for instance as a possible fetal metabolic biomarker during pregnancy. Full article

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Open AccessArticle

Dilemmas in Considering β-Thalassemia Status in Subjects with Borderline HbA₂ Values: A Pilot Study in Eastern India

by Tridip Chatterjee, Amit Chakravarty and Sudipa Chakravarty

Thalass. Rep. 2014, 4(2), 2103; https://doi.org/10.4081/thal.2014.2103 - 29 Sep 2014

Viewed by 385

Abstract

Interpreting hemoglobin disorders by high performance liquid chromatography can sometimes deceptive, especially with borderline HbA₂ values. It is often problematic, especially in antenatal cases if the partner is a known thalassemia trait. We tested for underlying β-thalassemia mutations in 24 subjects with [...] Read more.

Interpreting hemoglobin disorders by high performance liquid chromatography can sometimes deceptive, especially with borderline HbA₂ values. It is often problematic, especially in antenatal cases if the partner is a known thalassemia trait. We tested for underlying β-thalassemia mutations in 24 subjects with borderline HbA₂ values (between 3.0%-4.0%). Amplification refractory mutation system-polymerase chain reaction was used to detect the five common Indian β-thalassemia mutations: [IVS-I-5 (G>C), Cod 15 (G-A), Cod 8/9 (+G), Fr. 41/42 (-TTCT) and Cod 26 (G-A)]. β-globin gene sequencing was performed if no mutation was detected. β-globin gene defect was not identified in any of the samples. There was no presence of any of the five common mutations in the small cohort. The average value of HbA₂ in 24 normal samples was found to be 3.96. The average values for mean cell volume and mean cell hemoglobin (MCH) were found to be 82 and 28.8 pg respectively. Among these 24 normal samples, 13 had MCH below 27 pg and 11 had MCH above 27 pg. On the contrary, one thalassemic family was screened, in which the father of an HbE-β thalassemia patient was found to have HbA₂ 3.1, being a β-thalassemia carrier. Mutation analysis should be offered to all at-risk couples with borderline HbA₂, especially those with values between 3.5% and 4.0% and microcytic hypochromic indices. As, cases with some specific mutational background or clinical condition shows abnormally low HbA₂, so mutation screening should be performed in other partner if one partner found to be carrier or patient of thalassemia. Full article

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Open AccessArticle

Iron Chelating Agents for Iron Overload Diseases

by Guido Crisponi, Valeria Marina Nurchi and Maria Antonietta Zoroddu

Thalass. Rep. 2014, 4(2), 2046; https://doi.org/10.4081/thal.2014.2046 - 29 Sep 2014

Cited by 10 | Viewed by 459

Abstract

Although iron is an essential element for life, an excessive amount may become extremely toxic both for its ability to generate reactive oxygen species, and for the lack in humans of regulatory mechanisms for iron excretion. Chelation therapy has been introduced in clinical [...] Read more.

Although iron is an essential element for life, an excessive amount may become extremely toxic both for its ability to generate reactive oxygen species, and for the lack in humans of regulatory mechanisms for iron excretion. Chelation therapy has been introduced in clinical practice in the seventies of last century to defend thalassemic patients from the effects of iron overload and, in spite of all its limitations, it has dramatically changed both life expectancy and quality of life of patients. It has to be considered that the drugs in clinical use present some disadvantages too, this makes urgent new more suitable chelating agents. The requirements of an iron chelator have been better and better defined over the years and in this paper they will be discussed in detail. As a final point the most interesting ligands studied in the last years will be presented. Full article

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Open AccessArticle

Raman Spectroscopy Technology to Monitor the Carotenoids in Skin of Thalassemia Patients: A Novel Non-Invasive Tool Relating Oxidative Stress with Iron Burden

by Anna Perrone, Luisa Tesoriere, Anna Maria Pintaudi, Alessandro Attanzio, Paolo Rigano, Aurelio Maggio and Maria Antonietta Livrea

Thalass. Rep. 2014, 4(2), 1967; https://doi.org/10.4081/thal.2014.1967 - 29 Sep 2014

Cited by 4 | Viewed by 377

Abstract

In this work we approach the relationship between redox state and iron overload by noninvasive instrumental techniques. Intracardiac, liver iron and liver fibrosis have been monitored in transfusion-dependent thalassemia patients by magnetic resonance imaging and hepatic transient elastography examinations. These measurements have been [...] Read more.

In this work we approach the relationship between redox state and iron overload by noninvasive instrumental techniques. Intracardiac, liver iron and liver fibrosis have been monitored in transfusion-dependent thalassemia patients by magnetic resonance imaging and hepatic transient elastography examinations. These measurements have been matched with a non-invasive, and yet unexplored in clinical practice, evaluation of body’s oxidative stress through measurement of antioxidant carotenoids in skin, by a spectroscopic method based on Raman technology (RRS). The global body’s antioxidant status results from a balance between the level of antioxidants in cells and body fluids, including blood, and pro-oxidant species endogenously produced or coming from external sources. On this basis, the level of skin carotenoids can be considered a biomarker of the entire antioxidant status. In our work the use of RRS method provided information on the redox state of thalassemia patients, which was correlated with the iron status of the patients. Due to the highly adverse effects of accumulated iron, the novel, simple, non-invasive RRS to monitor dermal carotenoids with high compliance of the patients may be a useful tool for the management of thalassemia patients. Full article

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Open AccessArticle

The Role of Thalassemia International Federation in the Promotion, of Global, Regional and National Policy of Control of Hemoglobin Disorders: A Brief Overview

by Androulla Eleftheriou

Thalass. Rep. 2014, 4(2), 1963; https://doi.org/10.4081/thal.2014.1963 - 29 Sep 2014

Viewed by 334

Abstract

Improving global health remains the target of many international, regional and national official health bodies struggling to coordinate limited economic and human resources in order to ensure equal access of all to quality healthcare [...] Full article

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Open AccessObituary

Obituary—In memory of Prof. Renzo Galanello

by Andrea Mosca

Thalass. Rep. 2014, 4(2), 1961; https://doi.org/10.4081/thal.2014.1961 - 29 Sep 2014

Viewed by 294

Abstract

Prof. Renzo Galanello, a worldwide expert in thalassemic syndromes, died in Cagliari after a few months of a severe illness on 13 May 2013, at the age of 65 [...] Full article

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Open AccessReview

Control of Thalassemia in India

by Roshan B. Colah and Ajit Gorakshakar

Thalass. Rep. 2014, 4(2), 1955; https://doi.org/10.4081/thal.2014.1955 - 29 Sep 2014

Cited by 5 | Viewed by 936

Abstract

The β-thalassemias and sickle cell disorders pose a major health burden in the large and diverse Indian population. Education programs for awareness generation are being done by National Institutions, non-governmental organizations and Thalassemia Societies in different states. Several extensive epidemiological studies have shown [...] Read more.

The β-thalassemias and sickle cell disorders pose a major health burden in the large and diverse Indian population. Education programs for awareness generation are being done by National Institutions, non-governmental organizations and Thalassemia Societies in different states. Several extensive epidemiological studies have shown that there are many non-tribal and tribal communities where the prevalence of b-thalassemia carriers is much higher (5.3 to 17.0%) than the average of 3 to 4% projected for the entire country. These variations have also been shown within small geographic regions in some states, emphasizing the need for micro mapping to estimate the true burden of disease. There are 10 to 12 centers where prenatal diagnosis for hemoglobinopathies is done and the Indian Council of Medical Research is establishing additional regional centers in states where they are most needed. Sixtyeight b-thalassemia mutations have been described so far among Indians and the knowledge on their prevalence and regional distribution has helped to undertake prenatal diagnosis in a cost effective way. Full article

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Open AccessCase Report

Thalassemia and the Heartquake

by Caterina Borgna-Pignatti, Anna Tarocco, Alessandro Baldan and Alessandro Fucili

Thalass. Rep. 2014, 4(2), 1941; https://doi.org/10.4081/thal.2014.1941 - 29 Sep 2014

Viewed by 274

Abstract

On May 2012 the city of Ferrara and the surrounding region were hit by several earthquakes. We had the chance to observe the behavior of one thalassemic heart during the shocks, because of a 24-h electrocardiogram recording had been put in place a [...] Read more.

On May 2012 the city of Ferrara and the surrounding region were hit by several earthquakes. We had the chance to observe the behavior of one thalassemic heart during the shocks, because of a 24-h electrocardiogram recording had been put in place a few hours before the shocks. Full article

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Open AccessArticle

γA Gene Repeats Polymorphism for the Analysis of Haplotypes of Abnormal Hemoglobins

by Nejat Akar, Kadir Sipahi, Ece Akar and Erkan Yilmaz

Thalass. Rep. 2014, 4(2), 1935; https://doi.org/10.4081/thal.2014.1935 - 29 Sep 2014

Cited by 1 | Viewed by 330

Abstract

Aim of this study was to analyze γ A gene repeat polymorphism for the analysis of haplotypes of hemoglobin (Hb) variants such as Hb S, Hb D-Punjab, Hb O-Arab. Sickle cell cases had mainly Benin and Arab/Indian haplotype. We found three different haplotypes [...] Read more.

Aim of this study was to analyze γ A gene repeat polymorphism for the analysis of haplotypes of hemoglobin (Hb) variants such as Hb S, Hb D-Punjab, Hb O-Arab. Sickle cell cases had mainly Benin and Arab/Indian haplotype. We found three different haplotypes among Hb S, Hb O Arab and Hb D-Punjab cases. We named these three variants as Anatolian-1 and Anatolian-2 and Asian. Our data revealed that Hb O Arab may arise twice one from Asia and the other from Europe. Full article

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Open AccessReview

The Role of Magnetic Resonance Imaging in the Evaluation of Thalassemic Syndromes: Current Practice and Future Perspectives

by Sophie Mavrogeni, George Markousis-Mavrogenis and Genovefa Kolovou

Thalass. Rep. 2014, 4(2), 1859; https://doi.org/10.4081/thal.2014.1859 - 29 Sep 2014

Viewed by 294

Abstract

Iron can be deposited in all internal organs, leading to different types of functional abnormalities. However, myocardial iron overload that contributes to heart failure remains one of the main causes of death in thalassemia major. Using magnetic resonance imaging, tissue iron is detected [...] Read more.

Iron can be deposited in all internal organs, leading to different types of functional abnormalities. However, myocardial iron overload that contributes to heart failure remains one of the main causes of death in thalassemia major. Using magnetic resonance imaging, tissue iron is detected indirectly by the effects on relaxation times of ferritin and hemosiderin iron interacting with hydrogen nuclei. The presence of iron in the human body results in marked alterations of tissue relaxation times. Currently, cardiovascular magnetic resonance using T2* is routinely used in many countries to identify patients with myocardial iron loading and guide chelation therapy, specifically tailored to the heart. Myocardial T2* is the only clinically validated non-invasive measure of myocardial iron loading and is superior to surrogates such as serum ferritin, liver iron, ventricular ejection fraction and tissue Doppler parameters. Finally, the substantial amelioration of patients’ survival, allows the detection of other organs’ abnormalities due to iron overload, apart from the heart, missed in the past. Recent studies revealed that iron deposition has a different pattern in various parenchymal organs, which is independent from serum ferritin and follows an individual way after chelation treatment application. This new upcoming reality orders a closer monitoring of all organs of the body in order to detect preclinical lesions and early apply adequate treatment. Full article

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Open AccessArticle

Preimplantation HLA Typing for Stem Cell Transplantation Treatment of Hemoglobinopathies

by Anver Kuliev, Oleg Verlinsky and Svetlana Rechitsky

Thalass. Rep. 2014, 4(2), 1853; https://doi.org/10.4081/thal.2014.1853 - 29 Sep 2014

Cited by 1 | Viewed by 433

Abstract

Preimplantation genetic diagnosis (PGD) for HLA typing is steadily becoming an option for at risk couples with thalassemic children, requiring HLA matched bone marrow transplantation treatment. The paper presents the world’s largest PGD experience of 475 cases for over 2 dozens thalassemia mutations, [...] Read more.

Preimplantation genetic diagnosis (PGD) for HLA typing is steadily becoming an option for at risk couples with thalassemic children, requiring HLA matched bone marrow transplantation treatment. The paper presents the world’s largest PGD experience of 475 cases for over 2 dozens thalassemia mutations, resulting in birth of 132 unaffected children. A total of 146 cases were performed together with preimplantation HLA typing, resulting in detection and transfer of HLA matched unaffected embryos in 83 of them, yielding the birth of 16 HLA matched children, potential donors for their affected siblings. The presented experience of HLA matched stem cell transplantation for thalassemia, following PGD demonstrated a successful hematopoietic reconstitution both for younger and older patients. The data show that PGD is an efficient approach for HLA matched stem cell transplantation treatment for thalassemia. Full article

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Open AccessReview

The Thalassemia International Federation: A Global Public Health Paradigm

by Elpidoforos S. Soteriades and David Weatherall

Thalass. Rep. 2014, 4(2), 1840; https://doi.org/10.4081/thal.2014.1840 - 29 Sep 2014

Cited by 2 | Viewed by 439

Abstract

Many international organizations are struggling today to coordinate limited economic and human resources in support of governments’ efforts to advance public health around the world. The United Nations and the World Health Organization, along with others play a pivotal role in this global [...] Read more.

Many international organizations are struggling today to coordinate limited economic and human resources in support of governments’ efforts to advance public health around the world. The United Nations and the World Health Organization, along with others play a pivotal role in this global effort. Furthermore, during the past few decades an increasingly higher percentage of global efforts on public health are carried out by specific health initiatives, international projects and non-governmental patient-oriented organizations. The Thalassemia International Federation (TIF) is one such organization focusing on the control of thalassemia around the world. The current paper aims at presenting a comprehensive overview of the mission, goals, objectives and activities of this organization. Our ultimate goal is to highlight TIF’s public health paradigm and diffuse its success at an international levels for others to follow. TIF is devoted to disseminating information, knowledge, experience and best practices around the world to empower patients with thalassemia and their relatives, support health professionals providing care to such patients and promote national and international policies, which secure equal access to quality care for all patients with thalassemia. Full article

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Open AccessArticle

Differential Regulation of Plasma Proteins between Members of a Family with Homozygous HbE and HbEβ-thalassemia

by Suchismita Halder, Tridip Chatterjee, Amit Chakravarty, Sudipa Chakravarty and Abhijit Chakrabarti

Thalass. Rep. 2014, 4(2), 1837; https://doi.org/10.4081/thal.2014.1837 - 29 Sep 2014

Viewed by 330

Abstract

In this report we’ve compared the plasma protein profiles of 4 individuals in a family. Father and the younger son both are hemoglobin (Hb) Eβ-thalassemic {Cod 26 (G-A)/IVS 1- 5 (G-C)}, but the father never requires transfusion, whereas the younger son requires monthly [...] Read more.

In this report we’ve compared the plasma protein profiles of 4 individuals in a family. Father and the younger son both are hemoglobin (Hb) Eβ-thalassemic {Cod 26 (G-A)/IVS 1- 5 (G-C)}, but the father never requires transfusion, whereas the younger son requires monthly blood transfusion. Mother and the elder son are HbEE {Cod 26 (G-A)/Cod 26 (GA)} without any history of transfusion. Proteomic study was done on the plasma fraction of the blood following ammonium sulphate precipitation. Proteins were separated by 2D-gel electrophoresis, expression of proteins compared by densitometry and proteins identified by tandem MALDI mass spectrometry. Proteins responsible in hemolysis, hypercoagulation and hemoglobin scavenging have shown differential regulation, establishing the relation between the differences in the levels of plasma proteins with the progression of the disease phenotype, manifested in the extent of transfusion dependence of the patient. Full article

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Open AccessReview

HbA₂ Measurements in β-Thalassemia and in Other Conditions

by Giovanni Ivaldi, Giuseppina Barberio, Cornelis L. Harteveld and Piero Giordano

Thalass. Rep. 2014, 4(2), 1832; https://doi.org/10.4081/thal.2014.1832 - 29 Sep 2014

Cited by 3 | Viewed by 468

Abstract

Quite a few papers have been written on the significance of elevated hemoglobin (Hb) A₂ as a parameter for the diagnosis of β-thalassemia trait, on the cutoff values to be used in diagnostics and on the significance and effects of factors reducing [...] Read more.

Quite a few papers have been written on the significance of elevated hemoglobin (Hb) A₂ as a parameter for the diagnosis of β-thalassemia trait, on the cutoff values to be used in diagnostics and on the significance and effects of factors reducing or elevating the expression of HbA₂ and last but not least on the need for reliable measurement methods and precise calibrations with accurate standards. However, little has been published on the causes that elevate or reduce the HbA₂ levels in β- and a-thalassemia and in other conditions. For a better understanding of the value of a precise measurement of this parameter we summarize and elucidate in this review the direct and indirect mechanisms that cause the variations in HbA₂ expression and that influence the value of this parameter in particular conditions. We conclude by explaining the advantages and disadvantages of trusting on a precise measurement in the complete diagnostic contest. Full article

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Open AccessArticle

Providing Appropriate Genetic Information to Healthy Multi-Ethnic Carriers of Hemoglobinopathy in The Netherlands

by Piero C. Giordano, Natasha B.D. Binda, Antonio Amato, Egbert Bakker and Cornelis L Harteveld

Thalass. Rep. 2014, 4(2), 1822; https://doi.org/10.4081/thal.2014.1822 - 29 Sep 2014

Viewed by 401

Abstract

The aims of this study are: (i) to enquire whether informing healthy hemoglobinopathy carriers about their condition is a welcome initiative in The Netherlands; (ii) to study whether using information letters and thorough explanation is associated with presence or absence of undesired feelings [...] Read more.

The aims of this study are: (i) to enquire whether informing healthy hemoglobinopathy carriers about their condition is a welcome initiative in The Netherlands; (ii) to study whether using information letters and thorough explanation is associated with presence or absence of undesired feelings or emotions. We have approached 100 multi-ethnic carriers previously diagnosed in our lab. All subjects had previously received our information letter through their physician who was supposed to have provided an explanation of the letter if required. We have enquired whether the subjects had experienced negative or positive emotions after receiving our diagnosis and explanation and to which degree, if they were sufficiently informed and satisfied and if they would have considered prevention in case of risk. The rate negative versus positive feelings was calculated using a numerical distribution. We have registered negative feelings in a rate that was directly proportional to the lack of information. While the number of registered negative feelings in well-informed carriers was very low it was more present in badly informed. Nevertheless, all participants found carrier information a welcome initiative and over 80% of them declared to be in favor of prenatal diagnosis in case of risk. Carrier information is essential for an informed reproductive choice and is welcome in a multi-ethnic society. Unfortunately, information is not always consequently provided and should therefore be imbedded in the ongoing national screening for Rhesus and infectious diseases available to all women in early pregnancy. Full article

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Thalass. Rep., Volume 4, Issue 2 (September 2014) – 23 articles

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