Bilateral maculopathy in a thalassemia patient on iron chelation therapy: a case report / Maculopatia bilateral em paciente com talassemia em terapia quelante de ferro: relato de caso

ABSTRACT A 10-year-old Malay girl with underlying HbE/beta-thalassemia, on regular blood transfusion and deferoxamine iron chelation therapy, presented with two-month history of bilateral blurring of vision. On examination, her vision was 6/36 both eyes. Other optic nerve functions were normal. Anterior segment examination of both eyes was unremarkable. Fundus examination of both eyes revealed dull foveal reflex. Optical coherence tomography of both maculae showed increased central subfield thickness. Fundus fluorescence angiography showed patchy hypofluorescence over macular region for both eyes and late staining, indicating retinal pigment epithelium anomalies. A diagnosis of iron-chelation-therapy-related bilateral maculopathy was made. Patient was co-managed with pediatric hematology team to adjust the dose of deferoxamine, and was given three monthly appointments to monitor the progression of maculopathy at the ophthalmology clinic. However patient defaulted ophthalmology follow-up after the first visit.

RESUMO Uma menina malaia de 10 anos de idade com doença de base- B/beta-talassemia, em transfusão de sangue regular e terapia quelante de ferro deferoxamina, apresentou história de dois meses de visão turva bilateral. Ao exame, sua visão era de 6/36 em ambos os olhos. Outras funções do nervo óptico estavam normais. O exame do segmento anterior de ambos os olhos foi normal. Exame do fundo de ambos os olhos revelou reflexo foveal opaco. A tomografia de coerência óptica de ambas as máculas mostrou aumento da espessura do subcampo central. A angiografia de fluorescência do fundo mostrou hipofluorescência irregular sobre a região macular de ambos os olhos e coloração tardia, indicando anomalias de epitélio pigmentar da retina. Um diagnóstico de maculopatia bilateral relacionada à terapia quelante de ferro foi feito. A paciente foi avaliada em conjunto com a equipe de hematologia pediátrica para ajustar a dose de deferoxamina, e foram oferecidas três consultas mensais na clínica oftalmológica, para monitorar a progressão da maculopatia. No entanto, ela não compareceu para acompanhamento oftalmológico após a primeira visita.

Avaliação de variantes do gene TMPRSS6 e sua relação com o status de ferro em condições de eritropoese normal e aumentada / Evaluation of TMPRSS6 genetic variants and its relationship with iron status of women with normal and increased erythropoiesis

Introdução: A deficiência de ferro é frequente entre mulheres na idade reprodutiva e é considerada problema de saúde pública mundial. Por outro lado, patologias associadas com aumentada atividade eritropoética e sobrecarga de ferro, como as talassemias e a anemia falciforme, estão entre as doenças monogênicas mais frequentes em muitas populações. Os genes HFE e TMPRSS6 codificam as proteínas hemocromatose hereditária (HFE) e matriptase-2 (MT2) que, no fígado, modulam a produção de hepcidina, o hormônio regulador central do metabolismo de ferro. O objetivo deste estudo foi avaliar a relação entre o consumo alimentar de ferro, as variantes rs855791 (MT2736V), rs4820268 (MT2521V), rs1799945 (HFE63D) e rs1800562 (HFE282Y) e o status corporal do mineral entre mulheres com atividade eritropoética normal (aparentemente saudáveis) ou levemente aumentada (com ß-talassemia menor). Casuística e métodos: Inicialmente, foram incluídas 127 estudantes universitárias na idade reprodutiva (18 a 42 anos) e em aparente balanço estacionário do ferro corporal (necessidades fisiológicas e consumo alimentar de ferro pouco variáveis há pelo menos 12 meses). Em um segundo estudo, foram incluídos 33 casos de ß-talassemia menor (18 na pós-menopausa), registrados em serviços de hematologia de dois hospitais de São Paulo-SP e um de Sorocaba-SP. Essas foram pareadas com 66 controles, segundo idade, índice de massa corporal, status reprodutivo e uso de anticoncepcionais hormonais. A partir de inquéritos feitos com registros alimentares ou recordatórios de 24 horas foi estimado o consumo de ferro total e biodisponível. Amostras de sangue foram utilizadas para a extração de DNA e determinações de ferritina sérica, saturação da transferrina e hemoglobina. As genotipagens do TMPRSS6 e do HFE foram realizadas por PCR em tempo real. Resultados: Considerando as 226 mulheres avaliadas, as frequências dos alelos MT2736V, MT2521D, HFE63D e HFE282Y foram estimadas em 40,3%, 44,0%, 16,3% e 1,5% respectivamente. No primeiro estudo, foi estimada média de consumo de ferro 10 de 10,9 mg/dia e prevalência de deficiência do mineral de 12,6%. Estimativas de consumo de ferro biodisponível, mas não de ferro total, foram correlacionadas com os valores de ferritina e saturação da transferrina. As associações entre a biodisponibilidade dietética de ferro e seus biomarcadores foram especialmente evidentes entre as carreadoras da variante HFE63D, indicando uma significante interação gene-nutriente. Por outro lado, valores relativamente menores de saturação da transferrina foram associados à presença do alelo MT2736V, independentemente do consumo de ferro biodisponível. Mulheres com ß-talassemia menor e suas controles não diferiram quanto à frequência das variantes TMPRSS6 e HFE ou à biodisponibilidade dietética de ferro. Na pós-menopausa, a ß-talassemia menor foi associada com valores duas vezes maiores de ferritina, 20% maiores de saturação da transferrina e com probabilidade 3,5 vezes maior de hiperferritinemia. Entretanto, para casos e controles na idade reprodutiva, foi estimada probabilidade de inadequação do consumo de 20,7% e prevalências de deficiência do mineral de 13,3% e 10,0%, respectivamente. Entre essas mulheres, o genótipo positivo ou negativo para a variante MT2736V foi também associado com diferenças nas médias de saturação da transferrina. No entanto, o contraste nesses valores foi relativamente maior entre as mulheres com ß-talassemia menor. Além disso, mais acentuada hipocromia acompanhou a presença da variante MT2736V nessa condição. Conclusão: Os achados sugerem que, entre mulheres com eritropoese normal ou com ß-talassemia menor, a variante MT2736V não afeta tão fortemente as reservas de ferro corporal como faz a adequação do consumo desse mineral. Ainda assim, a variante HFE63D pode modificar a relação da biodisponibilidade de ferro com seu status corporal e, portanto, ser um importante marcador preditivo de resposta diferencial à dieta. A variante MT2736V foi associada com menor disponibilidade de ferro na circulação de mulheres na idade reprodutiva e, entre aquelas com ß.;-talassemia menor, com indício de acentuada alteração morfológica dos eritrócitos

Introduction: Iron deficiency is common among women at childbearing age and it is regarded as a worldwide public health issue. On the other hand, disorders associated with increased erythropoietic activity and iron overload, such as thalassemias and sickle cell disease, are among the most frequent Mendelian diseases in many populations. HFE and TMPRSS6 genes encode the hereditary hemochromatosis protein (HFE) and the matriptase-2 (MT2) both of which modulate the hepatic production of hepcidin, the main hormone regulator of iron metabolism. The aim of this study was to evaluate the relationship among dietary iron intake, rs855791 (MT2736V), rs4820268 (MT2521D), rs1799945 (HFE63D) and rs1800562 (HFE282Y) genetic variants and body iron status of women with normal (apparently healthy) or slightly increased (ß-thalassemia minor) erythropoietic activity. Casuistic and methods: Initially, 127 university students at childbearing age (18 to 42 years old) and with steady state body iron (few variations on physiological requirements and dietary iron intake at least for the last 12 months) were included. In a second study, it was included 33 cases of ß-thalassemia minor (18 of them post-menopaused) registered in Hematology Services from two hospitals from São Paulo-SP and one from Sorocaba-SP. They were paired with 66 controls by age, body mass index, reproductive status and hormonal contraceptive use. Using food diaries or 24 hours food recalls, total and bioavailable dietary iron intakes were estimated. Blood samples were used for DNA extraction and for determinations of ferritin, transferrin saturation with iron and hemoglobin. TMPRSS6 and HFE genotyping were performed by real time PCR. Results: Considering all the 226 women studied, the allelic frequencies of MT2736V, MT2521D, HFE63D e HFE282Y genetic variants were em 40.3%, 44.0%, 16.3% e 1.5%, respectively. In the first study, a total dietary iron intake of 10.9 mg/day and an iron deficiency prevalence of 12.6% were estimated. There were correlations among ferritin and transferrin saturation values with estimates of bioavailable, but not of total dietary iron intake s. Associations between dietary iron bioavailability and iron biomarkers were especially evident among carriers of HFE63D variant, indicating a significant gene-diet interaction. On the other hand, lower levels of transferrin saturation were associated with the presence of MT2736V variant allele, irrespective of bioavailable iron intake. TMPRSS6 and HFE variants frequencies and dietary iron bioavailability estimates did not differ between women with ß-thalassemia minor and their controls. Among postmenopausal women, ß-thalassemia minor was associated with two times higher ferritin values, 20% higher transferrin saturation values and 3.5 times higher chance for hiperferritinemia. However, among cases and controls at childbearing age, it was estimated a probability of inadequacy in the dietary iron intake of 20.7% and iron deficiency prevalences of 13.3% and 10.0%, respectively. Among these women, a positive or negative genotype for MT2736V was also associated with differences in transferrin saturation. Nevertheless, the contrast between these values was relatively higher among women with ß-thalassemia minor. Moreover, a more accentuated hypochromia accompanied the presence of the MT2736V variant in this condition. Conclusions: Our findings suggest that, among women with normal erythropoiesis or ß-thalassemia minor, the presence of the MT2736V variant does not strongly impact the body iron stores as does dietary iron adequacy. Nevertheless, the HFE63D variant may modify the relationship between the dietary iron bioavailability and the body iron status. Therefore, it might be an important predictive marker of women's differential response to diet. The MT2736V variant was associated with lower availability of circulating iron in women at childbearing age and, among those with ß-thalassemia minor, with suggestive accentuated morphological alteration of erythrocytes

Quality of life among Iranian patients with beta-thalassemia major using the SF-36 questionnaire / Qualidade de vida em pacientes iranianos com beta-talassemia maior usando o questionario SF-36

CONTEXT AND OBJECTIVE Patients with beta-thalassemia major (β-TM) experience physical, psychological and social problems that lead to decreased quality of life (QoL). The aim here was to measure health-related QoL and its determinants among patients with β-TM, using the Short Form-36 (SF-36) questionnaire. DESIGN AND SETTING Cross-sectional study at the Hematology Research Center of Shiraz University of Medical Sciences, in southern Iran. METHODS One hundred and one patients with β-TM were randomly selected. After the participants' demographics and disease characteristics had been recorded, they were asked to fill out the SF-36 questionnaire. The correlations of clinical and demographic factors with the QoL score were evaluated. RESULTS There were 44 men and 57 women of mean age 19.52 ± 4.3 years (range 12-38). On two scales, pain (P = 0.041) and emotional role (P = 0.009), the women showed significantly lower scores than the men. Lower income, poor compliance with iron-chelating therapy and presence of comorbidities were significantly correlated with lower SF-36 scores. These factors were also found to be determinants of worse SF-36 scores in multivariate analysis. CONCLUSIONS We showed that the presence of disease complications, poor compliance with iron-chelating therapy and poor economic status were predictors of worse QoL among patients with β-TM. Prevention and proper management of disease-related complications, increased knowledge among patients regarding the importance of managing comorbidities and greater compliance with iron-chelating therapy, along with psychosocial and financial support, could help these patients to cope better with this chronic disease state. .

CONTEXTO E OBJETIVO Pacientes com beta-talassemia maior (β-TM) vivenciam problemas físicos, psicológicos e sociais que levam à diminuição da qualidade de vida (QV). O objetivo foi determinar a QV relacionada à saúde e seus determinantes em pacientes com β-TM, utilizando questionário SF-36 (Short Form-36). TIPO DE ESTUDO E LOCAL Estudo transversal no Centro de Hematologia e Pesquisa em Universidade de Ciências Médicas de Shiraz, no sul do Irã. MÉTODOS Foram selecionados aleatoriamente 101 pacientes com β-TM. Após registro demográfico e características da doença, eles foram convidados a preencher o questionário SF-36. A correlação entre fatores clínicos e demográficos com escore de QV foi avaliada. RESULTADOS Havia 44 homens e 57 mulheres, com idade média de 19,52 ± 4,3 (variação 12-38) anos. Em duas escalas, dor (P = 0,041) e aspectos emocionais (P = 0,009), as mulheres apresentaram escores significativamente menores aos dos homens. Menor renda, baixa adesão à terapia quelante de ferro e presença de comorbidades foram correlacionadas com escores SF-36 significativamente menores. Esses fatores foram também considerados determinantes de piores escores de SF-36 em análise multivariada. CONCLUSÕES Mostramos que a presença de complicações da doença, a baixa adesão ao tratamento da terapia quelante de ferro e o baixo status econômico são preditores de pior QV em pacientes com β-TM. Prevenção e manejo adequado das complicações relacionadas com a doença, aumento do conhecimento dos pacientes sobre a importância do gerenciamento de comorbidades e ter maior adesão ao tratamento quelante de ferro, considerando também ...

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.

[Hearing status of thalassemic patients treated with deferoxamine]

Major beta thalassemia is the most common inherited anemia with high prevalence in Iran and hearing loss is one of its side effects. The present study aimed to determine the hearing status of patients with major thalassemia and its relationship with serum ferritin level, period of blood transfusion and deferoxamine administration. This descriptive-analytic study was performed on 80 thalassemia major patients [36 Male and 44 Female] aged 4-32 [14.2 +/- 2.3] who were referred to Bou Ali Hospital for two years. The studied variables include age, gender, serum ferritin level, amount and duration of Desferal injection and hearing level. All subjects went under evaluation for their otologic and audiometric status. The collected data were analyzed using t-test and ANOVA with SPSS software. The findings of the study indicated that 38 patients [47%] had entirely hearing loss. Among these 38 patients, 17 patients had sensory neural type f hearing loss 12 patients had conductive and 7 patients had mixed type of hearing problems. The results showed a significant relationship [p<0.05] between hearing loss and serum ferritin level and the dosage and duration of Desferal administration. Hearing impairment may develop with increasing dosage of deferoxamine. Periodic follow up and physical examination is recommended to prevent hearing impairment in major thalassemia

Comparison between deferoxamine and combined therapy with deferoxamine and deferiprone in iron overloaded thalassemia patients

Iron overload is the main cause of morbidity and mortality in patients with beta thalassemia major. Effective and convenient iron chelation remains one of the main targets of clinical management of thalassemia major. The combined treatment with deferoxamine and deferiprone could have an increased chelation efficacy and allow drug doses and toxicity to be reduced. Eighty patients with thalassemia major were randomized to receive one of the treatments: deferoxamine given in combination with deferiprone and deferoxamine alone. Changes in serum ferritin and any toxicity were determined. After one year, the mean serum ferritin [ +/- SD] in deferoxamine alone group decreased from 2945 [ +/- 591] ng/ml to 2,451 [ +/- 352] ng/ml [p<0.001]. In the group treat with deferoxamine and deferiprone, a dramatical decline was noticed from 2986 [ +/- 612] ng/ml to 2,082 [ +/- 221] ng/ml [p<0.001]. A significant improvement was observed after 6 months of combination therapy. The main side-effects were skin reactions [deferoxamine alone], nausea and arthralgia [combined therapy]. Combination therapy is a practical and effective procedure to decrease severe iron overload in patients with beta thalassemia major

[Determination of gamma-globin induction levels by different concentrations of hydroxyurea in K 562 cell lines for beta thalassemia treatment

Hydroxyurea [HU] is currently used for beta thalassemia treatment through induction of fetal gamma-globin, In this study, effects of different concentrations of hydroxyurea on induction of gamma-globin gene in K562 cells, and inhibitory effect of siRNA against candidate gene which may be involved in HU mediated gamma-globin induction were assessed. In this eperimantal study, K562 cells were treated by different concentrations of HU [0, 50, 100 and 200 microM]. siRNA against candidate gene in HU mediated gamma-globin gene induction was transfected to K562 cells using lipofectamine 2000. The level of gammal-globin gene induction and inhibition were determined by quantitavie real-time PCR. There were 1.75-, 2.45- and 2.55- fold inductions in gamma-globin gene using 50, 100 and 200 microM HU, respectively. There has been 79.5% down regulation on candidate gene in siRNA transfected K562 cells. This study showed that gamma-globin induction in 100 microM HU is similar to 200 micro M HU treated K562 cells. There was also efficient inhibitory effect on candidate gene which may be involved in HU mediated gamma-globin induction

Hydroxyurea can reduce or eliminate transfusion requirements in children with major and intermediate thalassemia

Hydroxyurea [HU] is a well known chemotherapeutic agent that has been used largely for various myeloproliferative diseases over the past 20 years. In beta-thalassemia, the effect of HU is much less clear and remains controversial. This study was undertaken to describe the hematologic and clinical responses of thalassemia major and intermediate patients to HU treatment during 2 years. Seventy one major and twenty transfusion-dependent intermediate thalassemia participants were selected among 150 beta-thalassemia patients. All patients underwent laboratory tests, and the state of energy, social activity, tolerance, and mood were recorded in the beginning of the study. Echocardiography was carried out before and during treatment with HU. All patients were treated with HU; the initial dose was 10-15mg/kg/day given once a day. All the patients tolerated HU well and showed a dramatic response to the drug. Nine of 20 intermediate and 8 of 71 major patients became completely transfusion free. In 6 intermediate and 15 major patients, transfusion interval prolonged more than 50%. After treatment, 95% of intermediate and 81% of major patients described an increase in social activity. HU therapy was also associated with a marked decrease in serum ferritin level in major thalassemia patients. HU may be administered in thalassemia major and intermediate patients to minimize or obviate the need for regular transfusion and concomitant iron overload. HU therapy appears to be safe and effective when administrated in thalassemia patients

Thyroid function in beta-thalassemic children receiving hypertransfusions with suboptimal iron-chelating therapy.

A cross-sectional study of thyroid function, free thyroxine (FT) and thyrotropin (TSH) concentrations, was carried out in 51 transfusion-dependent beta-thalassemic patients receiving suboptimal iron-chelating therapy. Nine patients had normal FT4 levels with elevated TSH levels (5.9-15.6 mLU/L), consistent with the diagnosis of compensated primary hypothyroidism and giving a prevalence of abnormal thyroid function of 17.6%. All patients with abnormal thyroid function had negative thyroid antibodies. No particular risk factor for abnormal thyroid function could be identified. Of the nine patients with compensated primary hypothyroidism, one patient showed a further increase in TSH level after 1 year of follow-up. The results of the present study emphasize the importance of thyroid function monitoring in hypertransfused beta-thalassemic patients.

Current status of iron overload and chelation with deferasirox.

A large number of complications in thalassemia major are due mainly to iron overload. Deferoxamine in iron-overloaded patients has established that chelation therapy, when given at an adequate dose, reduces iron-related complications. Parenteral administration and the daily nuisance of an infusion pump hinder the optimal compliance. Deferiprone is moderately effective oral iron chelator. Arthralgia and cytopenias constitute the main side effects. Deferasirox is a new orally effective iron chelator which has been shown to be non-inferior to deferoxamine in clinical trials. Further clinical trials especially in Indian children will tell if it stands the test of time.

Exjade (ICL 670): A new oral iron chelator.

ICL670(deferasirox) is a tridentate oral iron chelator that has shown high efficacy and theraputic safety in preclinical and currently ongoing phase III clinical evaluation. The drug has been just approved by US FDA for use in iron-loading anaemias. It is an ideal once-daily oral chelator, the effective dose of which is between 20 and 40 mg/kg. Iron is chelated & excreted almost exclusively via the feces. This is a major advance in the field of iron chelation.

The benefits of vitamin C and vitamin E in children with beta-thalassemia with high oxidative stress.

The present study aimed to determine the benefits of vitamin C and vitamin E as antioxidant supplements in beta-Thalassemia children who are at risk of iron overload due to multiple blood transfusion and high oxidative stress. Antioxidant status, oxidative products, plasma free hemoglobin, total hemoglobin and bilirubin were discussed. Twenty children who had laboratory confirmation of major beta-Thalassemia at least 6 months with history of packed red cell transfusion without iron chelation were recruited. The informed consent for blood sample collection and antioxidant medication was performed. Most patients (85%) had hyperferritinemia and all of them had high oxidative stress. All of them had low vitamin C and vitamin E level at recruitment. Three months after vitamin C and vitamin E supplementation, plasma vitamin C, vitamin E and glutathione were significantly increased, while total bilirubin was slightly decreased without significance. Other parameters included total antioxidant status (TAS), plasma and erythrocyte malondialdehyde (MDA), hemoglobin and plasma free hemoglobin had no differences during the study period. CONCLUSION: B-Thalassemia major children who had multiple blood transfusion are at risk in iron overload and high oxidative stress. From the present study, no significant improvement in raising hemoglobin and concerning low dose vitamin C is not contraindication in beta-Thalassemia patients. Therefore, vitamin C plus vitamin E supplementation have benefits more than vitamin E alone in promoting antioxidant status and may enhance liver function as total bilirubin tends to decrease.

Wheat grass juice reduces transfusion requirement in patients with thalassemia major: a pilot study.

Wheat grass juice is the juice extracted from the pulp of wheat grass and has been used as a general-purpose health tonic for several years. Several of our patients in the thalassemia unit began consuming wheat grass juice after anecdotal accounts of beneficial effects on transfusion requirements. These encouraging experiences prompted us to evaluate the effect of wheat grass juice on transfusion requirements in patients with transfusion dependent beta thalassemia. Families of patients raised the wheat grass at home in kitchen garden/pots. The patients consumed about 100 mL of wheat grass juice daily. Each patient acted as his own control. Observations recorded during the period of intake of wheat grass juice were compared with one-year period preceding it. Variables recorded were the interval between transfusions, pre-transfusion hemoglobin, amount of blood transfused and the body weight. A beneficial effect of wheat grass juice was defined as decrease in the requirement of packed red cells (measured as grams/Kg body weight/year) by 25% or more. 16 cases were analyzed. Blood transfusion requirement fell by >25% in 8 (50%) patients with a decrease of >40% documented in 3 of these. No perceptible adverse effects were recognized.

The activity of superoxide dismutase in hydroxyurea-treated E beta thalassemia.

AIM: To study the activity of superoxide dismutase (SOD) and the level of fetal hemoglobin (HbF) in hydroxyurea (HU)-treated E beta thalassaemia. METHODS: We have measured SOD level, HbF, mean corpuscular volume (MCV), packed cell volume (PCV) and hemoglobin (Hb) of E beta thalassaemia treated with HU (dose 30 mg/kg/day) for consecutive 90 days. RESULT: The increase of HbF synthesis without increase of Hb was observed in HU-treated patients. CONCLUSION: The decreased SOD level in long term and low dose of HU therapy in E beta thalassaemia may have some role to inhibit superoxide radical of erythrocyte. HU may act as inhibitor for oxidative damage of red cell in E beta thalassaemia.

Cross over placebo control trial of dilazep in beta-thalassemia/hemoglobin E patients.

An attempt was made to find better symptomatic treatment for beta-thalassemia/hemoglobin E (beta-thal/Hb E) patients in order to reduce their blood demand. Oral administration of dilazep was prescribed for these patients and a clinical trial was conducted over a 2-year period as a cross over placebo control study. Seventeen beta-thal/Hb E patients were enrolled in the study. All of them received dilazep and placebo for 10 months at different periods of time and were taken care of by the same doctor throughout the study. The blood demand of the same patients during the period of receiving dilazep with the period of receiving placebo, was 1.5 +/- 1.8 U/10 months versus 2.2 +/- 2.6 U/10 months, respectively. Thus dilazep showed a benefit in decreasing the blood demand by about 50% although the results did not reach statistical significance (p = 0.1). There was a statistical difference in hemoglobin concentration of the patients receiving dilazep compared with placebo (p = 0.038). While receiving dilazep the mean +/- SD hemoglobin level was 5.82 +/- 0.8 g/dl, significantly higher than while receiving placebo (5.66 +/- 0.9 g/dl) (p = 0.038). The liver, and renal function tests, and cardiac enzyme levels of the patients showed no significant changes throughout the study. However, one case had a problem with bleeding following tooth extraction whilst receiving dilazep and needed 1 unit of blood transfusion. In conclusion, administration of dilazep to patients with beta-thal/Hb E increased the patients' hemoglobin and reduced their blood demand with few side effects.