Vascular endothelial growth factor and pulmonary hypertension in children with beta thalassemia major / Fator de crescimento endotelial vascular e hipertensão pulmonar em crianças com talassemia beta maior

Abstract Objective: The purpose of this study was to illustrate the association between vascular endothelial growth factor level and pulmonary artery hypertension in children with β-thalassemia major. Method: This case-control study was conducted on 116 children with β-thalassemia major; 58 of them had pulmonary artery hypertension. They were compared to 58 healthy children who were age and sex-matched (control group). Serum levels of vascular endothelial growth factor and echocardiographic assessment were done for all children. Results: Vascular endothelial growth factor serum level was significantly higher in children with β-thalassemia major with pulmonary artery hypertension than in those without pulmonary artery hypertension, as well as in control groups (p < 0.001). Vascular endothelial growth factor serum level had a significant positive correlation with pulmonary artery pressure and serum ferritin, as well as a significant negative correlation with the duration of chelation therapy. Logistic regression analysis revealed that elevated vascular endothelial growth factor (Odd Ratio = 1.5; 95% Confidence Interval, 1.137-2.065; p = 0.005) was an independent risk factor of pulmonary artery hypertension in such children. Vascular endothelial growth factor serum level at a cutoff point of >169 pg/mL had 93.1% sensitivity and 93.1% specificity for the presence of pulmonary artery hypertension in children with β-thalassemia major. Conclusion: Elevated vascular endothelial growth factor serum level is associated with pulmonary artery hypertension in children with β-thalassemia.

Resumo: Objetivo: A finalidade deste estudo foi exemplificar a associação entre o nível de fator de crescimento endotelial vascular e a hipertensão arterial pulmonar em crianças com talassemia beta maior. Método: Este estudo caso-controle foi realizado em 116 crianças com talassemia beta maior; 58 das quais apresentaram hipertensão arterial pulmonar em comparação com 58 crianças saudáveis pareadas por idade e sexo (grupo de controle). Os níveis séricos do fator de crescimento endotelial vascular e a avaliação ecocardiográfica foram realizados em todas as crianças. Resultados: O nível sérico do fator de crescimento endotelial vascular foi significativamente maior em crianças com talassemia beta maior com hipertensão arterial pulmonar que as crianças sem hipertensão arterial pulmonar e os grupos de controle (p < 0,001). O nível sérico do fator de crescimento endotelial vascular apresentou uma correlação positiva significativa com a pressão arterial pulmonar e a ferritina sérica e correlação negativa significativa com a duração da terapia de quelação. A análise de regressão logística revelou que o fator de crescimento endotelial vascular elevado (RC = 1,5; IC de 95%: 1,137-2,065; p = 0,005) foi um fator de risco independente de hipertensão arterial pulmonar nessas crianças. O nível sérico do fator de crescimento endotelial vascular no ponto de corte > 169 (pg/mL) apresentou 93,1% de sensibilidade e 93,1% de especificidade na presença de hipertensão arterial pulmonar em crianças com talassemia beta maior. Conclusão: O nível sérico do fator de crescimento endotelial vascular elevado está associado à hipertensão arterial pulmonar em crianças com talassemia beta.

Intraocular pressure in subjects with beta-thalassemia minor / Pressão intraocular em indivíduos com talassemia beta minor

ABSTRACT Purpose: Beta-thalassemia minor, a common hereditary blood disorder in Mediterranean countries such as Turkey, is associated with insulin resistance. Insulin resistance, in turn, can be associated with excessively high intraocular pressure and, therefore, intraocular pressure-induced blindness. This study aimed to investigate the intraocular pressure in subjects with beta-thalassemia minor. Methods: We conducted a cross-sectional study comprising of 203 subjects divided into two groups: beta-thalassemia minor (103) and healthy (100).Hemoglobin electrophoresis was performed and complete blood count, blood pressures, serum fasting glucose and insulin levels were measured. All subjects underwent ophthalmological examinations including intraocular pressure measurements. Results: Intraocular pressure in the subjects with beta-thalassemia minor was significantly lower than that in healthy subjects (p=0.007). Additionally, intraocular pressure was inversely correlated with hemoglobin A2 levels (p=0.001, r=-0.320). Serum insulin and systolic blood pressure were significantly higher in subjects with beta-thalassemia minor (p=0.03, p=0.009, respectively). Conclusion: Subjects with beta-thalassemia minor had lower intraocular pressure than healthy controls, suggesting beta-thalassemia minor may actually protect against high intraocular pressure.

RESUMO Objetivo: Beta-talassemia menor é uma doença hereditária comum no sangue em países mediterrâneos como a Turquia e está associada à resistência à insulina. A resistência à insulina por sua vez, pode estar associada à pressão intraocular excessivamente alta e, portanto à cegueira induzida pela pressão intraocular. Este estudo teve como objetivo investigar a pressão intraocular em indivíduos com beta-talassemia menor. Métodos: Foi realizado um estudo transversal compreendendo 203 indivíduos divididos em 2 grupos: beta-talassemia menor (103) e saudável (100). Eletroforese de hemoglobina foi realizada e hemograma completo, pressão arterial, glicemia em jejum e níveis de insulina medidos. Todos os indivíduos foram submetidos foram submetidos a exames oftalmológicos, incluindo medidas de pressão intraocular. Resultados: A pressão intraocular nos indivíduos com beta-talassemia menor foi significativamente menor do que em indivíduos saudáveis (p=0,007). Além disso, a pressão intraocular foi inversamente correlacionada com os níveis de hemoglobina A2 (p=0,001, r=-0,320). Insulina sérica e pressão arterial sistólica foram significativamente maiores em indivíduos com beta-talassemia menor (p=0,03, p=0,009, respectivamente). Conclusão: Os indivíduos com beta-talassemia menor tiveram pressão intraocular menor do que os controles saudáveis, sugerindo que a beta-talassemia menor pode, na verdade, proteger contra a alta pressão intraocular.

Serum zinc level in children with beta-thalassemia major on iron chelator

Zinc as a second trace element of human body plays an important role in numerous functions Thalassemic patients are at risk of zinc deficiency due to various causes including the use of iron chelating agents oral or injectable. In this study we aim to measure the serum zinc level in beta-thalassemic patients on oral versus injectable iron chelator. A hospital based case control study conducted in the Center of Hereditary Blood Disorders in Al-Zahra Teaching Hospital for the period between 1st of December 2011 to 31th of Augest 2012. Seventy children with beta-thalassemia major were studied, patients were divided into two groups: 37 patients were treated by deferoxamine constituent of group A and 33 were those on deferasiroxe therapy constituent group B. Control group consisted of 35 healthy children. Serum zinc was measured by atomic absorption spectrophotometery. Patients aged between 5-11 years, boys were 34 and girls 36. The mean age of patients was 7.5 years. The mean serum zinc level in group A [patients on deferoxamine] 59.3784 +/- 28.44913 microg/dl was significantly lower than that of group B [patients on deferasiroxe] 105.5667 +/- 30.25488 microg/dl and control group 96.8974 +/- 24.98083 microg/dl respectively. Hypozincemia found in 70.7%, 20% and 17.9% in group A, B and control group respectively. There was a significant difference between patients of both groups and control [p<0.05], while high significant difference between patients of different iron chelators [p<0.001]. Hypozincemia is common in thalassemic patients. The low level of serum zinc mainly found in those with injectable iron chelator. Routine follow up of serum zinc level and other possible causes of hypozenicemia should be studied before giving zinc to these patients

Quantitative estimation of interferon-gamma levels among Egyptian polytransfused haematology cases

This study was designed to estimate interferon-gamma [INF-gamma] levels among polytransfused haematology cases. Cases were selected from the haematology unit of Alexandria main university hospital, Egypt. Complete blood counts, estimation of INF-gamma and hepatitis B and C virus [HBV and HCV] status were conducted on 20 unsplenectomized patients with thalassaemia major and 20 patients with acute myeloid leukaemia [AML] in the maintenance phase and 20 healthy subjects. Mean haemoglobin levels and red blood cell counts were significantly higher in the control group than the AML and thalassaemia groups, while white blood cell counts were significantly lower in the control group than the case groups. Two AML patients [10%] and 1 thalassaemia patient [5%] were HBV-positive, while 5% of both case groups were HCV-positive. Mean values of INF-? were significantly different between AML, thalassaemia major and control groups: 5517 [SD 1142] pg/mL, 1024 [SD 249] pg/mL and 2980 [SD 604] pg/mL respectively

Prevalence and hematological profile of β-thalassemia and sickle cell anemia in four communities of Surat city.

Background: From the data of transfusion-dependent thalassemia major cases, the 4 communities (Muslim, Dhodia Patel, Kachhiya Patel, and Modh Bania) with high prevalence but not studied methodically were selected. Aim: The aim of this study is to find prevalence of β-thalassemia and sickle cell anemia in 4 selected communities and also to evaluate hematological profile in them. Materials and Methods: For screening of β-thalassemia trait (BTT) and sickle cell trait (SCT), all samples were tested for red cell indices, solubility, HbA 2 level and doubtful cases confirmed on HPLC. Statistical Analysis: Mean ± SD, χ2 and 't' tests were used to evaluate the significance. Results and Conclusion: Among 4 selected communities, the highest prevalence of BTT was observed in Modh Bania (6.2%) and Kachhiya Patel (6.05%) and that of SCT in Dhodia Patel (14.0%). Significantly higher prevalence of BTT was observed in Memon ( P < 0.0001) and of SCT in Khalifa 6.6% ( P < 0.0001) compared to other Muslim sub castes. Anemia was more prevalent in BTT compared to non-BTT and non-SCT subjects. 80% of Dhodia Patel non-BTT and non-SCT subjects showed microcytic red cell morphology. Their Mean ± SD Hb concentration was 12.1 ± 1.73, hence iron deficiency cannot be a sole reason. This community needs α-thalassemia and iron studies.

A comparative study of hematological parameters of α and β thalassemias in a high prevalence zone: Saudi Arabia.

BACKGROUND AND AIMS: Saudi Arabia falls in the high prevalent zone of αα and β thalassemias. Early screening for the type of thalassemia is essential for further investigations and management. The study was carried out to differentiate the type of thalassemia based on red cell indices and other hematological parameters. MATERIALS AND METHODS: The study was carried out on 991 clinically suspected cases of thalassemias in Riyadh, Saudi Arabia. The hematological parameters were studied on Coulter STKS. Cellulose acetate hemoglobin electrophoresis and high-performance liquid chromatography (HPLC) were performed on all the blood samples. Gene deletion studies were carried out by restriction fragment length polymorphism (RFLP) technique using the restriction endonucleases Bam HI. STATISTICAL ANALYSIS: Statistical analysis was performed on SPSS 11.5 version. RESULTS: The hemoglobin electrophoresis and gene studies revealed that there were 406 (40.96%) and 59 (5.95 %) cases of β thalassemia trait and β thalassemia major respectively including adults and children. 426 cases of various deletion forms of α thalassemias were seen. Microcytosis was a common feature in β thalassemias trait and (-α/-α) and (--/αα) types of α thalassemias. MCH was a more significant distinguishing feature among thalassemias. β thalassemia major and α thalassemia (-α/αα) had almost normal hematological parameters. CONCLUSION: MCV and RBC counts are not statistically significant features for discriminating between α and β thalassemias. There is need for development of a discrimination index to differentiate between α and β thalassemias traits on the lines of discriminatory Indices available for distinguishing β thalassemias trait from iron deficiency anemia.

Results from transcranial Doppler examination on children and adolescents with sickle cell disease and correlation between the time-averaged maximum mean velocity and hematological characteristics: a cross-sectional analytical study / Resultados do estudo do Doppler transcraniano em crianças e adolescentes portadores de doença falciforme e correlação entre a velocidade média máxima e características hematológicas: um estudo transversal analítico

CONTEXT AND OBJECTIVE: Transcranial Doppler (TCD) detects stroke risk among children with sickle cell anemia (SCA). Our aim was to evaluate TCD findings in patients with different sickle cell disease (SCD) genotypes and correlate the time-averaged maximum mean (TAMM) velocity with hematological characteristics. DESIGN AND SETTING: Cross-sectional analytical study in the Pediatric Hematology sector, Universidade Federal de São Paulo. METHODS: 85 SCD patients of both sexes, aged 2-18 years, were evaluated, divided into: group I (62 patients with SCA/Sß0 thalassemia); and group II (23 patients with SC hemoglobinopathy/Sß+ thalassemia). TCD was performed and reviewed by a single investigator using Doppler ultrasonography with a 2 MHz transducer, in accordance with the Stroke Prevention Trial in Sickle Cell Anemia (STOP) protocol. The hematological parameters evaluated were: hematocrit, hemoglobin, reticulocytes, leukocytes, platelets and fetal hemoglobin. Univariate analysis was performed and Pearson's coefficient was calculated for hematological parameters and TAMM velocities (P < 0.05). RESULTS: TAMM velocities were 137 ± 28 and 103 ± 19 cm/s in groups I and II, respectively, and correlated negatively with hematocrit and hemoglobin in group I. There was one abnormal result (1.6 percent) and five conditional results (8.1 percent) in group I. All results were normal in group II. Middle cerebral arteries were the only vessels affected. CONCLUSION: There was a low prevalence of abnormal Doppler results in patients with sickle-cell disease. Time-average maximum mean velocity was significantly different between the genotypes and correlated with hematological characteristics.

CONTEXTO E OBJETIVO: Doppler transcraniano (DTC) detecta risco de acidente vascular cerebral (AVC) em crianças com anemia falciforme (AF). O objetivo foi avaliar os resultados ao DTC nos diferentes genótipos da doença falciforme (DF) e correlacionar a velocidade média-máxima (VMMáx) às características hematológicas. TIPO DE ESTUDO E LOCAL: Estudo transversal analítico realizado no setor de Hematopediatria da Universidade Federal de São Paulo. MÉTODOS: 85 pacientes com DF, 2-18 anos, ambos os sexos, foram avaliados e divididos em: grupo I (62 com AF ou Sß0 talassemia); e grupo II (23 com hemoglobinopatia SC ou Sß+ talassemia). DTC foi realizado e revisado por um único investigador usando um aparelho de ultrassonografia Doppler com transdutor de 2MHz, conforme critérios do protocolo STOP (Stroke Prevention Trial in Sickle Cell Anemia). As variáveis hematológicas avaliadas foram: hematócrito, hemoglobina, reticulócitos, leucócitos, plaquetas, hemoglobina fetal. Análise univariada e coeficiente de Pearson calculados para parâmetros hematológicos e VMMáx, P < 0,05. RESULTADOS: As média das VMMáx foram de 137 ± 28 cm/s e 103 ± 19 cm/s nos grupos I e II, respectivamente. Houve correlação negativa da VMMáx com hematócrito e hemoglobina no grupo I. Houve um (1,6 por cento) resultado anormal e 5 (8,1 por cento) condicionais no grupo I; no grupo II, todos estavam normais. Artérias cerebrais médias foram as únicas acometidas. CONCLUSÃO: Houve baixa prevalência de resultados anormais ao DTC em pacientes com DF. A VMMáx foi significativamente diferente entre os genótipos da DF e apresentou correlação com variáveis hematológicas.

Chelation therapy with desferrioxamine does not normalize ferritin level but attenuates oxidative damage and improves total antioxidant level in malaysian Chinese β-thalassaemia major patients / La terapia de quelación con deferoxamina no normaliza los niveles de ferritinaa pero atenúa el daño oxidativo y mejora el nivel antioxidante total en los pacientes sinomalayos que padecen de talasemia β

Beta-thalassaemia major causes severe anaemia and patients with it may be transfusion-dependent for life. Regular blood transfusions cause iron-overload that leads to oxidative damage which can hasten mortality. The objective of this research was to study the oxidant-antioxidant indices in β-thalassaemia major patients at the University of Malaya Medical Centre (UMMC) who were on desferrioxaminechelation or without chelation therapy. Blood was collected from 39 Chinese patients and 20 controls. Plasma and peripheral blood mononuclear cell lysates (PBMC) were extracted and biochemical tests to evaluate oxidative stress were performed. Oxidative stress was evident in these patients as advanced oxidized protein products (AOPP) and lipid hydroperoxides were elevated, whereas glutathione peroxidase activity and the ferric reducing antioxidant power (FRAP) were reduced. The catalase activity in the patients' PBMC was elevated, possibly as a compensatory mechanism for the reduced glutathione peroxidase activity in both red blood cells and PBMC. The lower FRAP and higher AOPP levels in the non-chelated patients compared with the chelated patients were indicative of a lower oxidative stress level in the chelated patients. The ferritin levels in the chelated and non-chelated patients were high and the mean levels of liver enzyme activities in the majority of patients were elevated regardless of chelation therapy. In conclusion, this study indicates that desferrioxamine chelation therapy does not normalize ferritin level but attenuates oxidative damage and improves total antioxidant level in Malaysian Chinese β-thalassaemia major patients.

La beta-talasemia mayor causa anemia severa, y los pacientes con este padecimiento pueden hacerse dependientes de las transfusiones de sangre por el resto de sus vidas. Las transfusiones regulares de sangre dan lugar a una sobrecarga de hierro que conduce al dano oxidativo, el cual a su vez puede acelerar la mortalidad. El objetivo de esta investigación fue estudiar las tasas de oxidantesantioxidantes en pacientes de beta-talasemia mayor en el Centro Médico de la Universidad de Malaya, tanto aquellos bajo tratamiento de quelación con deferoxamina, como aquellos sin terapia de quelación alguna. Se recogieron muestras de sangre de 39 pacientes chinos y 20 controles. Se extrajeron plasma y lisados de celulas mononucleares perifericas (CMSP), y se realizaron pruebas bioquimicas para evaluar el estrés oxidativo. El estrés oxidativo era evidente en estos pacientes en forma de productos avanzados de oxidación de proteinas (PAOP), y los hidroperoxidos de lipidos eran elevados, en tanto que la actividad de glutatión peroxidasa y el poder reductor ferrico/antioxidante (FRAP) era reducida. La actividad de la catalasa en los pacientes de CMSP era elevada, posiblemente como un mecanismo compensatorio frente a la actividad de glutatión peroxidasa reducida tanto en los globulos rojos como en las CMSP. Los niveles más bajos de FRAP y los más altos de PAOP en los pacientes no quelados en comparación con los pacientes quelados, indicaban un bajo nivel de estrés oxidativo en los pacientes quelados. Los niveles de ferritina tanto en los pacientes quelados como en los no quelados, eran altos, y los niveles promedio de actividades enzimaticas del higado fueron elevados en la mayoria de los pacientes, independientemente de la terapia de quelación. En conclusión, este estudio indica que la terapia de quelación con deferoxamina no normaliza el nivel de ferritina, pero en cambio atenua el daño oxidativo, y mejora el nivel antioxidante total en los pacientes sinomalayos afectados por la betatalasemia mayor.

Soluble transferrin receptors in the diagnosis of iron deficiency anemia, beta thalassemia minor and beta thalassemia minor with concomitant iron deficiency anemia

Iron deficiency anemia and beta thalassemia minor are two important causes of microcytic and hypochromic anemia, beta thalassemia minor with concomitant iron deficiency anemia make the diagnosis difficult through conventional laboratory tests. Determination of soluble transferrin receptors is a helpful laboratory test for the diagnosis with certainty. Purpose of this study was to evaluate the role of soluble transferrin receptors in the differentiation of iron deficiency anemia from beta thalassemia minor. A total of 80 subjects were enrolled in this study. They were divided into four groups i.e. 20 normal adult male, 20 normal adult female, 20 patients with iron deficiencyanemia group and 20 patients with beta thalassemia minor. Patients with beta thalassemia minor were further sub grouped in beta thalassemia minor with and without concomitant iron deficiency anemia. Soluble transferrin receptors were determined by ELISA technique using Quantikine IVD kit [R and D Systems]. Levels of sTfR in individuals with beta thalassemia minor were increased but these were lower than in iron deficiency anemia group. Mean sTfR levels were higher in patients with beta thalassemia minor and concomitant iron deficiency anemia than in normal subjects as well as in patients with beta thalassemia minor alone. Their levels were similar to those in patients with iron deficiency anemia. sTfR can be used as a discriminating marker between patients with iron deficiency anemia and beta thalassemia minor alone. Care must be taken while dealing the patients with beta thalassemia minor and concomitant iron deficiency anemia

Clinical, hematologic and molecular variability of sickle cell-β thalassemia in western India.

BACKGROUND: Sickle cell-β thalassemia (HbS-β thalassemia) is a sickling disorder of varying severity, which results from compound heterozygosity for sickle cell trait and β thalassemia trait. The present study was undertaken to determine the genetic factors responsible for the clinical variability of HbS-β thalassemia patients from western India. MATERIALS AND METHODS: Twenty-one HbS-β thalassemia cases with variable clinical manifestations were investigated. The α and β globin gene clusters were studied by molecular analysis. RESULTS: Thirteen patients showed milder clinical presentation as against eight patients who had severe clinical manifestations. Four β thalassemia mutations were identified: IVS 1-5 (G→C), codon 15 (G→A), codon 30 (G→C) and codon 8/9 (+G). α thalassemia and XmnI polymorphism in homozygous condition (+/+) were found to be common among the milder cases. The βS chromosomes were linked to the typical Arab-Indian haplotype (#31). Framework (FW) linkage studies showed that four β thalassemia mutations were associated with different β globin gene frameworks. Linkage of codon 15 (G→A) mutation to FW2 is being observed for the first time. CONCLUSION: The phenotypic expression of HbS-β thalassemia is not uniformly mild and α thalassemia and XmnI polymorphism in homozygous condition (+/+) are additional genetic factors modulating the severity of the disease in the Indian subcontinent.

Serum zinc level in thalassemia major

To compare serum zinc level between Thalassemia Major [TM] patients and normal population at Shafa Hospital in South West of Iran. A total of 25 male and 36 female of TM patients were enrolled in this study. Out of 61 patients thirty were treated by deferroxamine [DFO] and 31 were on the combination of DFO and deferiprone [DEF] protocol therapy. Sixty normal subjects of the matching age and gender were recruited as controls. From each patient and control group 2 ml of blood was taken in fasting condition. Cell blood count and serum zinc were carried out for both thalassemia patients and normal subjects. The mean age of patients and control group was 15 +/- 5years. Mean serum zinc level was 68.97 +/- 21.12microg/dl, 78.10 +/- 28.50 microg/dl, and 80.16 +/- 26.54 microg/dl in the TM with DFO, TM with DFO + DEF combination protocol and control group respectively. There was no significant correlation between patients and control group. However 50 percent of TM with DFO, 38.7 percent of TM with DFO + DEF and 32.8 percent of control group had hypozincemia. Nearly 40 to 50 percent of TM patients and one third of normal subjects are suffering from hypozincemia. This study shows that low level of serum zinc is a health problem in both thalassemia patients and normal population in South West of Iran

effect of aerobic rehabilitation program on concentration of ferritin, iron, tibc and cardiovascular operation in the young patients suffering from major thalassemia

Thalassemia is a type of genetic disease that is classified in the group of heritable anemia. Due to anemia hemoglobin level decreases and blood transfusion is used to composed that finally results in excessive iron content. In order to eliminate the excessive iron, Desfral is prescribed. The excessive iron creates undesirable complications on liver, heart and endocrine glands tissues. The most important complication in the patients suffering from thalassemia is restrictive cardiomyopathy and rhythm disorders and cardiac blockage insufficiency. Determination of the effect of aerobic rehabilitation program on density of Ferritin, Iron, TIBC and cardiovascular operation in the young adult patients with major thalassemia. This research performed in semi experimental method on 15 patients 10 to 16 yearsold suffering from thalassemia with history of 9 to 15 years were studied in a 50- individual population. Research process for these patients was performed in three sections of pretest, during test and posttest. Research data were analyzed with correlation method and X[2] test. Average blood ferritin after first sport test and an eight-week aerobic program was decreased considerably as compared with rest [P<0.05] and blood iron after sport test and after aerobic practices as compared with rest time showed significant decreased [P<0.05]. In heart beat frequency domain in the duration of rest after aerobic practices, progressive decrease was observed [P<0.05]. The effective aerobic rehabilitation program in patients with major thalasemia should be managed based on medical examination and balk sport test. Despite of the creasing aeron and ferritin load, it can cause a freshness mentality during blood transfusion and desferal administration physical practices in the safe physiologic domain, the harmful effect of excessive iron on heart decreases and therefore their cardiovascular operation improves

Assessment of the relation between hypothyroidism and serum level of ferritin in beta thalassemia patients

Beta-thalassemia Major is one of the most common diseases in Iran especially in Golestan province. Blood transfusion has many important complications such as endocrine disorders and Hypothyriodism which can result in disability and untimely mortality. This study was designed to determine the association between Hypothyroidism and serum level of ferritin in these patients. This study was performed on all patients in thalassemia center of Gorgan [n=l85] with age range of 1-37 years. During five years, level of ferritin and T[3], T[4], TSH were measured every three and 12 months respectively. Data were analyzed using SPSS software. Thirty patients had hypothyroidism. Mean age was 17.8 years and male/female ratio was 1. Five patients were under the age of 10. The average level of ferritin at the onset of complication was 2528.400 +/- 2157.300 ng/ml. Serum level of ferritin in hypothyroidism, had shown a significant difference in comparison to non-hypothyroid patients [p<0.05]. This study showed that to prevent hypothyroidism in major thalassemia, we could start clinical and para-clinical studies, such as checking serum level of ferritin. Although endocrine abnormalities are usually sought in patients over 10 years of age, we recommend starting the endocrine screening at age 5 since we had 5 patients under the age of ten with these abnormalities

Decreased nucleoside transport and hENT1 transporter expression in beta-thalassemia major

This study investigated nucleoside transport activity and transporter polypeptide expression in erythrocytes from beta-thalassemia major patients to determine if inhibition of transport activity is a sensitive indicator of oxidative membrane damage. Blood samples were obtained from 54 patients, diagnosed as having beta-thalassemia major prior to therapeutic transfusion, and 20 normal subjects. Uptake of 3H-uridine into washed erythrocytes was measured at room temperature using short incubation periods [5 s] and a rapid inhibitor oil stop protocol. Erythrocyte membranes were analyzed by SDS-PAGE and nucleoside [hENT1] and glucose [GLUT-1] transporter polypeptides quantitated on immunoblots. Uridine uptake was significantly lower in beta-thalassemic cells than in normal erythrocytes [20.03 +/- 1.08 pmol/108 cells/ 5 s, mean +/- SEM, n = 31, vs. 31.15 +/- 1.21 pmol/108 cells/5 s, n = 20; p < 0.0001]. Expression of hENT1 was significantly lower in beta-thalassemic cells [23.90 +/- 1.01 arbitrary units, n = 54] than in controls [101.20 +/- 2.43 arbitrary units, n = 20; p < 0.001] but expression of GLUT-1 was not changed appreciably [101.80 +/- 2.43 arbitrary units, n = 54, for thalassemic cells; 102.60 +/- 3.02 arbitrary units, n = 20, for control cells; p = 0.87]. Erythrocytes from beta-thalassemia major patients showed decreased uridine transport which was associated with decreased nucleoside transporter expression. The process[es] mediating a selective decrease in hENT1 polypeptides in beta-thalassemia major was/were not determined

Intervention and prevention of hereditary hemolytic disorders in India: a case study of two ethnic communities of Sundargarh district in Orissa.

OBJECTIVES: This study was aimed at to sensitize, motivate, and screen two major vulnerable tribal communities--Bhuyan and Kharia, for hemoglobinopathies and allied hemolytic disorders, along with prospective and retrospective genetic/marriage counseling to the affected persons. For sustainability, imparting of relevant training to local paramedical staff, and to undertake periodic follow up for evaluation, intervention and clinical management through local PHCs/hospitals. METHODOLOGY: Tribal people in Orissa live in clusters practicing inter-village marriages following tribal endogamy and clan exogamy. The random sampling procedure for the selection of whole village was followed. Population of each tribe was representative because incoming and outgoing married women represent other surrounding villages belonging to their community. The pre- and post-intervention knowledge, attitude and practice (KAP) studies were conducted. Sensitization, motivation and education for carrier detection were carried out through IEC materials, holding interactive meetings and discussions at district, block and village levels. Standard biochemical and hematological techniques were followed for analysis of blood samples. Relevant training to local health personnel was imparted. Both prospective and retrospective intervention and genetic/marriage counseling was done through local PHC doctor. RESULTS: Study revealed high occurrence of hemoglobinopathies in Bhuyan (9.8%) and Kharia (13.3%) tribes, including uncommon hemoglobin variants like hemoglobin D, E, beta-thalassemia, and hereditary persistence of fetal hemoglobin (HPFH). G-6-PD enzyme deficiency was high in Dhelki Kharia (30.7%) and in Dudh Kharia (19.2%), whereas, it was recorded to be 21.1%, 16.3% and 13.7% in Paraja, Paik and Paudi Bhuyan subtribes, respectively. Use of antimalarials was cautioned in these tribal communities. Due to low frequency of Rhesus (D) negative (0.2-1.2%), the Rhesus (D) incompatibility problem seemed to be absent. Impact of methodical and prudent intervention and preventive strategies was found positive and encouraging. CONCLUSIONS: Adoption of a biomedical anthropological approach for implementing and evolving health seeking cooperative strategy that was tribal-oriented, tribal-friendly and tribal-participatory for intervention and prevention of common hemolytic disorders was found effective. Success of this strategy was apparent with overwhelming response of tribal people towards changing the traditional mindset, improving the health and quality of life. Health must meet the needs and perception of the people.

Role of interleukin-3 and signaling pathways on beta-thalassemia/HbE erythroid progenitor cell in culture.

In order to study the role of the cytokine interleukin-3 (IL-3) and its signaling pathways in erythropoiesis of beta-thalassemia/HbE erythroid progenitor cells, CD34 positive cells were isolated from peripheral blood of patients and healthy subjects. After culturing the cells in the presence or absence of IL-3, cell viability was measured by trypan blue staining and apoptotic cells were analyzed by flow cytometry. After 7 days of culture the highest percent erythroid progenitor cell viability was obtained with cells from healthy subjects, while the lowest percentage was found in those from splenectomized beta-thalassemia/HbE. Viability of beta-thalassemia/HbE erythroid progenitor cells in the presence of IL-3 was higher than that of nonsupplemented cells. In addition, specific inhibitors of protein kinase C (Ro-318220), phospholipase C (U-73122) and Janus kinase 2 (AG-490) were used to investigate the involvement of signaling pathways in erythropoiesis. Percent apoptosis of erythroid progenitor cells from splenectomized beta-thalassemia/HbE subjects treated with RO-318220 was higher than those of nonsplenectomized beta-thalassemia/HbE and healthy subjects. Treatment with U-73122 resulted in enhanced percent apoptotic cells from normal and beta-thalassemia/HbE subjects. All these effects were independent of IL-3 treatment.

Perfil hematológico de la beta-talasemia menor en Tucumán / Hematological profile of beta-thalassemia minor in Tucuman

La b-talasemia menor es uno de los desórdenes genéticos más comunes y constituye la principal causa de anemia hereditaria. Si se exceptúan las provincias de Buenos Aires y Santa Fe, es escasa la información bibliográfica acerca de la distribución de la talasemia en la Argentina. Dado que no existen registros sobre el perfil hematológico de la b-talasemia en la región noroeste de la Argentina, el propósito del presente trabajo fue realizar un estudio exploratorio descriptivo de las características hematológicas y electroforéticas de una población de la provincia de Tucumán portadora de b-talasemia. Se estudiaron 52 pacientes derivados para investigación de síndrome talasémico. Se realizó hemograma, reticulocitos, ferremia, electroforesis de hemoglobina, dosaje de hemoglobinas F y A2. En el 46% de los pacientes se confirmó el diagnóstico de rasgo b-talasémico, detectándose leve anemia con microcitosis y Hb A2 aumentada. El estudio del perfil hematológico no demostró diferencias significativas con respecto a edad y sexo y fue similar a lo ya publicado por otros autores. Según el origen étnico, la población estudiada estuvo constituida por un 58% de individuos de origen italiano, 34% de españoles y 8% de árabes, con predominio de la población italiana, similar a trabajos previos en la Argentina.

The b-thalassemia minor is one of the most common genetic blood disorder and it represents the main cause of hereditary anemia. There is scant information in the scientific literature about b-thalassemia minor distribution in Argentina, except for the provinces of Buenos Aires and Santa Fe. There is no published study of this disorder in the northwest of Argentina. The objective of this descriptive and explorative study is to determine the hematological and electrophoretic characteristics of a b-thalassemia minor population in the province of Tucumán. A total of 52 patients with suspected thalassemia syndrome were studied; haemogram, reticulocytes, serum iron, hemoglobin electrophoresis, hemoglobin F and hemoglobin A2 were performed. Forty-six percent of the patients presented a b-thalassemia minor diagnosis, with the following findings: mild anemia with microcytosis and elevated Hb A2. The hematological profile showed no significative differences with respect to age and sex, and it was similar to previous studies, published by different authors. The ethnic origins were as follow: Italians 58%, Spaniards 34% and Arabians 8%, with preponderance of the Italian population, similar to previous studies in Argentina.

Detection of beta-thalassemia (homozygous) by hemoglobin electrophoresis on agar gel and citrate agar medium: a case report.

A seven month old male baby was admitted to NICU of BPKIHS, Dharan with dyspnoea and distress. He was investigated for hemolytic anemia and suspected of beta Thalassemia (Homozygous) based on the low level of Hb and high HbF%. To investigate further, Hb electrophoresis was carried out using agar gel and citrate agar gel at pH 8.6 and 6.0 respectively along with control. Electrophoretogram showed single narrow band lagging behind the healthy control moved toward anode at pH 8.6 and single narrow band moved parallel to healthy control toward cathode at pH 6.0. Thus the diagnosis of betaThalassemia (Homozygous) is favored.