Thalassemia Research Papers - Academia.edu (original) (raw)

This is the protocol for a review and there is no abstract. The objectives are as follows:

To assess the risks and benefits of GH therapy in people with thalassaemia.

The current study was designed to determine some immunological and biochemical biomarkers in patients with thalassemia major (TM) and thalassemia intermedia (TI), 20 patients with thalassemia and 20 healthy volunteers as control group.... more

The current study was designed to determine some immunological and biochemical biomarkers in patients with thalassemia major (TM) and thalassemia intermedia (TI), 20 patients with thalassemia and 20 healthy volunteers as control group. The results have shown a significant increase in WBCs also a significant decrease in neutrophil activity and IFN- in TM and TI groups as compared to controls. The levels of Hb decrease in TM and TI groups as compared to controls, while a significant increase has been observed in platelets count. The results have also revealed a significant elevation in Iron and ferritin in TM and TI groups when compared with controls while Transferrin was decreased in the patients when compare with controls. The liver enzymes (AST and ALT) have shown significantly elevated activities in TM an TI groups.

To determine the prevalence, molecular characteristics and hematological study of thalassemia in Tha Kradarn Subdistrict Chachoengsao Province. The present study population consisted of266 participants from Moo 19 Baan Na-Ngam,... more

To determine the prevalence, molecular characteristics and hematological study of thalassemia in Tha Kradarn Subdistrict Chachoengsao Province. The present study population consisted of266 participants from Moo 19 Baan Na-Ngam, Chachoengsao Province, Thailand. After blood collection, all samples were screened for thalassemia by initial screening with the OF and DCIP tests and additional testing by CBC, RBC indices, hemoglobin typing and determination of Hb A2 and Hb E. All common alpha-thalassemia mutations were determined using the PCR with allele specific primers and Gap PCR for common deletions. The prevalence of alpha-thal 1, alpha-thal 2 and beta-thal were found as 2.72%, 11.26% and 0.97%, respectively. Regarding the abnormal hemoglobins, the prevalence of Hb E, Hb Constant Spring and Hb Pakse was 38.45%, 3.69% and 0.78%, respectively. MCV and MCH were significantly different between P-thalassemia as well as a-thal 1 carriers and normal subjects. In all alpha-thal 1 traits, it ...

Seven Italian centers reported data on survival, causes of death and appearance of complications in patients with thalassemia major. The interactions between gender, birth cohort, complications, and ferritin on survival and complications... more

Seven Italian centers reported data on survival, causes of death and appearance of complications in patients with thalassemia major. The interactions between gender, birth cohort, complications, and ferritin on survival and complications were analyzed. Survival after the first decade was studied for 977 patients born since 1960 whereas survival since birth and complication appearance was studied for the 720 patients born after 1970. Better survival was demonstrated for patients born in more recent years (p<0.00005) and for females (p=0.0003); 68% of the patients are alive at the age of 35 years. In the entire population 67% of the deaths were due to heart disease. There was a significant association between birth cohort and complication-free survival (p<0.0005). The prevalence of complications was: heart failure 6.8%, arrhythmia 5.7%, hypogonadism 54.7%, hypothyroidism 10.8%, diabetes 6.4%, HIV infection 1.7%, and thrombosis 1.1%. Lower ferritin levels were associated with a l...

X-linked thrombocytopenia with thalassemia (XLTT; Online Mendelian Inheritance in Man [OMIM] accession number 314050) is a rare disorder characterized by thrombocytopenia, platelet dysfunction, splenomegaly, reticulocytosis, and... more

X-linked thrombocytopenia with thalassemia (XLTT; Online Mendelian Inheritance in Man [OMIM] accession number 314050) is a rare disorder characterized by thrombocytopenia, platelet dysfunction, splenomegaly, reticulocytosis, and unbalanced hemoglobin chain synthesis. In a 4-generation family, the gene responsible for XLTT was mapped to the X chromosome, short arm, bands 11-12 (band Xp11-12). The maximum lod score possible in this family, 2.39, was obtained for markers DXS8054 and DXS1003, at a recombination fraction of 0. Recombination events observed for XLTT and markers DXS8080 and DXS8023 or DXS991 define a critical region that is less than or equal to 7.65 KcM and contains the gene responsible for the Wiskott-Aldrich syndrome (WAS; OMIM accession number 301000) and its allelic variant X-linked thrombocytopenia (XLT; OMIM accession number 313900). Manifestations of WAS include thrombocytopenia, eczema, and immunodeficiency. In WAS/XLT the platelets are usually small, and bleeding...

Ineffective erythropoiesis is a prominent defect leading to anaemic status in thalassaemic patients. Reticulocyte enumeration in the peripheral blood is a non-aggressive method of measuring bone marrow erythropoietic activity. We used an... more

Ineffective erythropoiesis is a prominent defect leading to anaemic status in thalassaemic patients. Reticulocyte enumeration in the peripheral blood is a non-aggressive method of measuring bone marrow erythropoietic activity. We used an automated reticulocyte counter (Sysmex R-3000) to determine the number and maturation level of circulating reticulocytes among various types of thalassaemia: non-splenectomized beta-thalassaemia/haemoglobin E (beta E) and splenectomized cases (beta E-S), classical haemoglobin H disease (H), haemoglobin H disease with haemoglobin Constant Spring (H/CS), homozygous haemoglobin Constant Spring (CS/CS), homozygous haemoglobin E (EE), heterozygous thalassaemics and other rare combinations. Haemoglobin H disease has a higher absolute count than beta-thalassaemia (beta E), indicating relatively better compensatory erythropoiesis in haemoglobin H disease. Those with CS genes (H/CS and CS/CS) have poorer reticulocyte maturation than any other type of thalassaemia with rather high absolute numbers, especially in H/CS. This indicates a severer degree of ineffective erythropoiesis in beta-thalassaemia (beta E), which reflects an insufficient rise in reticulocyte number in comparison with alpha-thalassaemia (H). The presence of haemoglobin Constant Spring is associated with abnormally low reticulocyte maturation due to enhanced erythrocyte production or direct effect of Constant Spring globin itself, both still unexplained with the current information. The splenectomized beta E has increased reticulocyte number and cells with high DNA content, probably nucleated red cells, designated as the upper particle count parameter. However, there is the same degree of reticulocyte maturation in non-splenectomized and splenectomized beta E patients, suggesting a role for splenic pooling of reticulocytes.

Structural hemoglobin (Hb) variants typically are based on a point mutation in a globin gene that produce a single amino acid substitution in a globin chain. Although most are of limited clinical significance, a few important subtypes... more

Structural hemoglobin (Hb) variants typically are based on a point mutation in a globin gene that produce a single amino acid substitution in a globin chain. Although most are of limited clinical significance, a few important subtypes have been identified with some frequency. ...

The essay reconstructs the antithalassemia campaign carried out by means of population screening and pre-marriage counseling for about twenty years in Italy, immediately after the relationship between microcythemia and Cooley's anemia... more

The essay reconstructs the antithalassemia campaign carried out by means of population screening and pre-marriage counseling for about twenty years in Italy, immediately after the relationship between microcythemia and Cooley's anemia had been established, as well as its genetic bases. We examine the Italian contributions to the understanding of the genetics and of the clinical treatment of thalassemic disorders, and analyze the approaches to prevention as well as the results obtained by the first campaign against a genetic disease, conceived and largely implemented in Italy by Ezio Silvestroni and Ida Bianco. We discuss the resistances met by the antithalassemia campaign due to the cultural and organizational backwardness of the Italian medical community and of the public health system. Moreover we analyze the explanations and interpretations of the problematic results of these experiences in terms of morbidity reduction. It will be pointed out that the objective of genetic cou...

GP.Mur is a clinically important red blood cell (RBC) phenotype in Southeast Asia. The molecular entity of GP.Mur is glycophorin B-A-B hybrid protein that promotes band 3 expression and band 3–AQP1 interaction, and alters the organization... more

GP.Mur is a clinically important red blood cell (RBC) phenotype in Southeast Asia. The molecular entity of GP.Mur is glycophorin B-A-B hybrid protein that promotes band 3 expression and band 3–AQP1 interaction, and alters the organization of band 3 complexes with Rh/RhAG complexes. GP.Mur+ RBCs are more resistant to osmotic stress. To explore whether GP.Mur+ RBCs could be structurally more resilient, we compared deformability and osmotic fragility of fresh RBCs from 145 adults without major illness (47% GP.Mur). We also evaluated potential impacts of cellular and lipid factors on RBC deformability and osmotic resistivity. Contrary to our anticipation, these two physical properties were independent from each other based on multivariate regression analyses. GP.Mur+ RBCs were less deformable than non-GP.Mur RBCs. We also unexpectedly found 25% microcytosis in GP.Mur+ female subjects (10/40). Both microcytosis and membrane cholesterol reduced deformability, but the latter was only obser...

RÉSUMÉ Les hémoglobinopathies, maladies génétiquement déterminées, sont de deux types. Dans les anomalies de structure, une hémoglobine (Hb) « anormale » est présente en quantité normale, entraînant ou non des signes fonctionnels. L'HbS,... more

RÉSUMÉ Les hémoglobinopathies, maladies génétiquement déterminées, sont de deux types. Dans les anomalies de structure, une hémoglobine (Hb) « anormale » est présente en quantité normale, entraînant ou non des signes fonctionnels. L'HbS, responsable de la drépanocytose, y a une place prépondérante. Les anomalies de synthèse, avec production en quantité diminuée d'Hb normale, constituent le groupe hétérogène des thalassémies. Les anomalies moléculaires présentes dans ces deux types de pathologiques sont souvent similaires (mutation ponctuelle, large délé-tion…). Cependant les mécanismes physiopathologiques mis en cause sont très différents. La diversité des mutations n'explique que très partiel-lement l'hétérogénéité de présentation clinique. Le diagnostic moléculaire des hémoglobinopathies occupe actuellement une place importante dans le cadre du diagnostic, du conseil génétique et du diagnostic prénatal mais il nécessite toujours au préalable une analyse phénotypique précise. SUMMARY Molecular bases of haemoglobin diseases Among haemoglobin diseases, two types are particularly important to consider : the structural abnormalities and the synthesis deficiencies. In structural anomalies, hemoglobin (Hb) " abnormal " is present in normal amounts, whether or not resulting functional signs. HbS, responsible for sickle cell disease, has a prominent place. Quantitative defect in the production amount of one of the globin sub-units, either total absence or marked reduction, constitute the heterogeneous group of thalassemia. Molecular abnormalities present in both types of disease are often similar (point mutation, deletion…). However, the pathophysiological mechanisms involved are very different. Multiple mutations are involved, but the severity of the disease is only partially related to the nature of the mutation. Molecular diagnosis of haemo-globinopathies currently plays an important role in the diagnosis, genetic counseling and prenatal diagnosis but it still requires prior specific phenotypic analysis.

makalah penyakit thalasemia

This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with... more

This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright Combined chelation treatment may be a better approach for transfusion-dependent thalassemia major patients with iron overload complications because of increased efficacy. Combination therapy with desferrioxamine and deferiprone has already been reported to improve survival dramatically by reversing cardiac dysfunction and other endocrine complications. Some patients have intolerance or inconvenience to parenteral desferrioxamine. The hypothesis of this study was that combining two oral chelators, deferiprone and deferasirox, might lead to similar results. Following approval by the hospital ethical committee and a written informed consent from each patient, 16 patients who fulfilled the criteria participated in a study protocol for a period of up to 2 years. Efficacy measures analysis demonstrated a statistically significant decrease of total body iron load as estimated by serum ferritin, LIC and MRI T2* indices. Regarding the safety assessment, the incidence of adverse events was minor compared to the associated toxicity of monotherapy of each drug. No new onset of iron overload-related complications was demonstrated. A reversal of cardiac dysfunction was observed in 2/4 patients, while the mean LVEF increased significantly. Regarding endocrine assessment, in 2/8 patients with impaired glucose tolerance, we noted a significant decrease in the mean 2 h glucose in OGTT. Additionally an improvement in gonadal function was observed and one male and one female gave birth to two healthy children without hormonal stimulation. Combined oral chelation in thalassemia offers the promise of easier administration, better compliance and may lead to an improvement of patient quality of life by preventing or even reversing iron overload complications.

Primary Pure red cell aplaisa is a syndrome due to failure of erythropoiesis, normocytic anemia with severe reticulocytopenia due to the marked reduction of erythroid precursors in the bone marrow. Johnson-Blizard syndrome is rare,... more

Primary Pure red cell aplaisa is a syndrome due to failure of erythropoiesis, normocytic anemia with severe reticulocytopenia due to the marked reduction of erythroid precursors in the bone marrow. Johnson-Blizard syndrome is rare, autosomal recessive or autosomal dominant, multisystem congenital disorder having abnormal development of pancreas, nose and scalp with mental retardation, hearing loss and growth failure. A case reported was a 3 months old male infant having prediagnosed primary pure red cell aplasia and Johnson-Blizard syndrome with marked pancreatic insufficiency. He presented with profuse greenish-bulky stools and severe pallor complexion. Homeopathic medicines Calcarea phos and Podophyllum was given in 3x potencies according to the sign and symptoms. Frequency of stool reduced within a month and his haemoglobin level also increased with passage of time. Medicine continued for almost 10 months and follow-up visits showed no recurrence of pure red cell aplasia. Homeopathic remedy Calcarea phos 3x is highly effective to increase the haemoglobin level and Podophyllum 3x is helpful to manage profuse stools

This is a concept about thalasemia

In addition to the severe beta thalassemias, hematologists have begun to recognize the more severe forms of alpha thalassemia, namely hemoglobin (Hb) H disease and Hb H/Hb Constant Spring, as well as the beta compound heterozygote, beta... more

In addition to the severe beta thalassemias, hematologists have begun to recognize the more severe forms of alpha thalassemia, namely hemoglobin (Hb) H disease and Hb H/Hb Constant Spring, as well as the beta compound heterozygote, beta thalassemia/HbE. Clinically, variably severe anemia becomes apparent in the first year accompanied by occasionally massive expansion of erythropoiesis. The most anemic patients require regular red blood cell transfusions to avoid death from cardiac failure. However, the inevitable iron accumulation leads to dysfunction, primarily involving the heart, liver, and endocrine system; thus, regularly transfused patients require iron chelation. A major discovery was that allogeneic bone marrow (stem cell) transplantation in severely affected subjects with both alpha and beta thalassemia could result in cure. Current work deals with specific complications, such as iron overload and endocrine, cardiopulmonary, thrombophilic, and osteopenic problems. The thalassemias are likely to benefit in the future from specific gene therapy. There are also important advances in genetic counseling based on results of early fetal diagnosis.

Ομιλία για την ιστορική πορεία της ιατρικής έρευνας για τη Μεσογειακή Αναιμία, κυρίως στην Ελλάδα. Η πρώιμη περίοδος ιατρικών ερευνών για τη διάγνωση και θεραπεία της ασθένειας διαρκεί από το 1925 μέχρι το 1950, η δεύτερη περίδος από το... more

Ομιλία για την ιστορική πορεία της ιατρικής έρευνας για τη Μεσογειακή Αναιμία, κυρίως στην Ελλάδα. Η πρώιμη περίοδος ιατρικών ερευνών για τη διάγνωση και θεραπεία της ασθένειας διαρκεί από το 1925 μέχρι το 1950, η δεύτερη περίδος από το 1950 μέχρι το 1975 και η τελευταία από το 1975 μέχρι σήμερα.

To provide recommendations to physicians, midwives, genetic counsellors, and clinical laboratory scientists involved in pre-conceptional or prenatal care regarding carrier screening for thalassemia and hemoglobinopathies (e.g., sickle... more

To provide recommendations to physicians, midwives, genetic counsellors, and clinical laboratory scientists involved in pre-conceptional or prenatal care regarding carrier screening for thalassemia and hemoglobinopathies (e.g., sickle cell anemia and other qualitative hemoglobin disorders). To determine the populations to be screened and the appropriate tests to offer to minimize practice variations across Canada. The Medline database was searched for relevant articles published between 1986 and 2007 on carrier screening for thalassemia and hemoglobinopathies. Key textbooks were also reviewed. Recommendations were quantified using the Evaluation of Evidence guidelines developed by the Canadian Task Force on Preventive Health Care. The evidence collected from the Medline search was reviewed by the Prenatal Diagnosis Committee of the Canadian College of Medical Geneticists (CCMG) and the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC). Screening ...

Background: The Maldives has the highest prevalence of thalassemia in the world. However, there is little research done on the psychosocial aspects of this illness. Objectives: This study aimed to examine health related quality of life... more

Background: The Maldives has the highest prevalence of thalassemia in the world. However, there is little research done on the psychosocial aspects of this illness. Objectives: This study aimed to examine health related quality of life (HRQOL) among adolescents with beta-thalassemia major attending the National Thalassemia and Other Hemoglobinopathies Centre (NTC), Maldives Blood Services, Maldives. Thus, appropriate recommendation could be proposed. Methods: A total of 81 adolescents (mean age 15.7 years) with beta-thalassemia major were engaged. HRQOL was assessed using the Pediatric Quality of Life Inventory (PedsQL). Other relevant information was gathered through interview or medical record. Results: The HRQOL was reduced. The mean for physical, emotional, social, school and psychosocial HRQOL was 80.50, 72.30, 88.18, 76.44, and 78.96, respectively. The total HRQOL was 79.50 and this was lower in females (75.29) compared to males (83.29). Ferritin levels of 1,001-2,499 μg/l and > 2,500 μg/l were noted in 34.2% and 53.9%, respectively. Good compliance was reported in 55% of participants. Conclusions: Adolescents with beta-thalassemia major in the Maldives have reduced HRQOL. The high ferritin level could reduce the HRQOL and hence an attempt should be made towards lowering ferritin and improving compliance to chelation treatments. The gender difference in HRQOL signifies the need for more attention to the female patients and for areas of improvement to be explored.

To evaluate if peak characteristics, the retention time, and percentage of total hemoglobin of an unknown peak on the Bio-Rad VARIANT II Hb A1c method may be used to establish a tentative identification of hemoglobin variants. The peak... more

To evaluate if peak characteristics, the retention time, and percentage of total hemoglobin of an unknown peak on the Bio-Rad VARIANT II Hb A1c method may be used to establish a tentative identification of hemoglobin variants. The peak characteristics, retention time, and percentage of total hemoglobin obtained on abnormal peaks found on the Bio-Rad VARIANT II Hb A1c method were tabulated and evaluated against the identification of the hemoglobin variant established by the Bio-Rad beta thalassemia HPLC method and hemoglobin electrophoresis at both acid and alkaline pH. Some hemoglobin variants show specific peak characteristics, retention times, and percentage of total hemoglobin on the Bio-Rad VARIANT II Hb A1c method that allows for tentative identification of the hemoglobin variant. The retention times and percentage of hemoglobin variant for the common hemoglobin variants E, D, S, and C obtained on the Bio-Rad VARIANT II Hb A1c method are tabulated below. Peak characteristics, r...

Pakistan has a high prevalence of β-thalassemia (β-thal) but lacks a screening program for its prevention. This questionnaire-based cross-sectional study was conducted in six randomly chosen non medical universities to assess the... more

Pakistan has a high prevalence of β-thalassemia (β-thal) but lacks a screening program for its prevention. This questionnaire-based cross-sectional study was conducted in six randomly chosen non medical universities to assess the students' knowledge of β-thal and premarital screening, and their attitude towards such a program. Comparison was made between the respondents' attitude towards premarital screening before and after providing them some information regarding the disease. Only 54.5% (207) of 380 students had heard of β-thal, with a mean knowledge score of 13.0 ± 4.4 out of 27 questions. Most respondents were aware of the concept of premarital screening. Out of 207 students, 60.4% wanted to know if they were carriers, 69.1% wanted to know their spouse's carrier status and 59.4% wanted premarital screening to be made mandatory in Pakistan. These figures increased to 72.5, 78.3 and 67.6%, respectively after provision of written information (p values: 0.03, 0.02, and ...

Minor beta thalassemia is a common condition in children. The aim of the present study was the investigation of serum tissue transglutaminase IgA level as potential celiac disease in patients with thalassemia minor. This case control... more

Minor beta thalassemia is a common condition in children. The aim of the present study was the investigation of serum tissue transglutaminase IgA level as potential celiac disease in patients with thalassemia minor. This case control study was conducted on patients with beta thalassemia minor and healthy children in the years of 2014 to 2015. A total of 300 children were enrolled and IgA and tissue transglutaminase IgA levels were measured. The normal limit of tissue transglutaminase IgA was considered to be 20 IU/mL. Data analysis was performed using SPSS20 with 95% confidence of interval. Two groups of participants were matched regarding sex (Chi-Square=0.436 and P=0.509). Mean age of participantswas8.46 ± 4.54 and 7.74 ± 2.99 in minor and control respectively. Means of age, body mass index and serum tissue transglutaminase values were different between case and control while only serum tissue transglutaminase was significant (P=0.024). The status of tissue transglutaminase had a significant correlation with case and control (P<0.001). It is concluded that a positive association exists between β-thalassemia minor and celiac disease. Based on this result we could suggest a routine screening test for celiac disease in all children with β-thalassemia minor.

β-thalassemia major (β –TM) is the most common thalassemia severe phenotype among Iranians. In recent years, molecular understanding of pathogenesis of β –TM has provided a great opportunity regarding diagnostic issues. Creating... more

β-thalassemia major (β –TM) is the most common thalassemia severe phenotype among Iranians. In recent
years, molecular understanding of pathogenesis of β –TM has provided a great opportunity regarding diagnostic
issues. Creating comprehensive molecular databases provides highly sensitive diagnostic tools for β –TM and
effective prenatal diagnosis (PND) molecular screening tests. Despite a large body of research on molecular
basis of β –TM, there are few review papers that consider a general view on the distribution of β –TM mutations
in Iran. In the current review, common genetic defects identified in Iranian β –TM patients since 2005 to 2014
have been described. In addition, the prevalences and distributional trends of recognized mutations were
discussed. It was found that IVSII-1 (G>A) and IVSI-5 (G>C) were by far the most frequent mutations detected
in Iranian patients. Other common reported mutations included FSC 8/9 (+G), IVS I-110 (G>A), FSC 36/37 (–
T), IVSI-1 (G>A), IVSI (-25bp), and codon 44 (-C). In conclusion, it was found that molecular profile of β –TM
is highly variable among different Iranian populations; in particular, it seems that ethnicity and intra-migration
can be most important participating factors in controlling distributional patterns.

Thalassaemia is a genetic disease in which there is a relative or complete lack of alpha or beta globin chains. Patients with moderate to severe forms of thalassaemia need transfusions from the early years of life. Antibody production... more

Thalassaemia is a genetic disease in which there is a relative or complete lack of alpha or beta globin chains. Patients with moderate to severe forms of thalassaemia need transfusions from the early years of life. Antibody production against blood group antigens may cause many problems in preparing compatible blood units for transfusion. The identification of definite blood group phenotypes by the haemagglutination method can be difficult because of the mixed population of red blood cells from the donor and recipient. Forty multiply transfused thalassaemic patients and ten healthy controls with no history of blood transfusion were enrolled in this study. Allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) and haemagglutination methods were used to determine the presence of Rhesus (Rh) C, c, E and e antigens. In this study four primer sets were used for ASO-PCR amplification of RhC/c and RhE/e. Although PCR assays for RhC/c and RHE/e genotyping have been described pr...