The Effect of Blood Transfusion on Growth of Patients with Hb E/β-Thalassemia

Abstract

A retrospective evaluation of growth in 112 patients (68 males, 44 females) with Hb E (HBB: c.79G>A)/β-thalassemia (β-thal), classified as 88 transfusion-dependent thalassemia (TDT) and 24 non transfusion-dependent thalassemia (NTDT), is reported. Patients with TDT have received regular transfusions of red blood cells (RBCs) 15?mL/kg every 4?weeks to maintain pre transfusion hemoglobin (Hb) levels of at least 9.0?g/dL and were categorized according to age at initiation of regular RBC transfusion as subgroup 1, <4?years; subgroup 2, 4–10?years, and subgroup 3, >10?years. Iron chelation was initiated at the mean age of 7?years. The results revealed that patients in subgroups 1 and 2, receiving RBC transfusions at a young age (2.9 and 6.9?years, respectively), had normal prepubertal growth at enrollment and last follow-up. Patients in subgroup 3, with the lowest initial height Z-score of ?2.10, were able to achieve comparable final adult height as those in subgroups 1 and 2. The mean final height of 21 males and 13 females with TDT at the ages of 18.9 and 18.7?years was 168.1 and 157.7?cm, respectively, which did not significantly differ from their midparental height and those with NTDT. Early initiation of optimal transfusion and iron chelation promoted normal prepubertal growth. However, delayed initiation of transfusion at age 12?years impaired prepubertal growth but they could achieve normal final adult height.     

Comparison of Quality of Life in Patients with β-Thalassemia Intermedia and β-Thalassemia Major in Southern Iran

Increased life expectancy in patients with β-thalassemia (β-thal) requires healthcare professionals to give greater attention to improving their quality of life (QoL). We aimed to evaluate health-related QoL (HRQoL) and its determinants in patients with β-thal intermedia (β-TI) compared with β-thal major (β-TM). In this cross sectional study, 118 patients with β-TI, referred to the Thalassemia Clinic of Shiraz University of Medical Sciences, Shiraz, Iran, were investigated by convenience sampling from January to June 2014 in southern Iran. A Short Form-36 (SF36) questionnaire was used. We had previously conducted a similar study in 101 patients with β-TM (12 to 38 years). Compared data of the two studies were analyzed. Mean age was 26.5?±?6.5 (12 to 48) years in β-TI and 19.5?±?4.4 (12–38) years in the β-TM group. The best scales of HRQoL were physical functionin (PF) (76.8?±?26.6) and bodily pain (BP) (70.1?±?24.8) in the β-TI group. Males had significantly better score only in vitality dimension compared to females (p?=?0.020). Higher education (p?=?0.023) in univariate analysis and age ≤20 years (B coefficient?=?13, p?=?0.008) in multivariate analysis showed significant relationships with higher total HRQoL score in β-TI. Comparison of β-TI and β-TM, after adjusting for covariates, total HRQoL was similar between the two groups. In evaluating the subscales, only PF showed a better condition in patients with β-TM [adjusted mean difference?=?12.5, 95% confidence interval (95% CI): 5.6–19.3, p?相似文献   

A Prospective Study of Cyclosporine A Treatment of Patients with Low-Risk Myelodysplastic Syndrome: Presence of CD55−CD59− Blood Cells Predicts Platelet Response

Although immunosuppressive therapy using antithymocyte globulin or cyclosporine A (CSA) is effective in selected patients with low-risk myelodysplastic syndrome, the response rates reported so far are inconsistent, and the indication of immunosuppressive therapy for myelodysplastic syndrome has not been clearly defined. We treated 20 myelodysplastic syndrome patients (17 refractory anemia cases [RA], 2 RA with excess blasts, and one RA with ringed sideroblasts) with 4 mg/kg per day of CSA for 24 weeks. Among the 19 patients evaluated, 10 showed hematologic improvement; 8 patients showed an erythroid response, 6 showed a platelet response, and one showed a neutrophil response. Most patients with hematologic improvement continued CSA thereafter, and the progressive response was observed until the latest follow-up (median, 30 months). Most toxicities associated with CSA usage were manageable, and no patient had developed acute leukemia up to this point. Short duration of illness, refractory anemia with minimal dysplasia determined by bone marrow morphology, and the presence of paroxysmal nocturnal hemoglobinuria-type cells were significantly associated with the platelet response. A minority of RA patients who did not possess such predictive variables achieved an isolated erythroid response. In conclusion, CSA may be a therapeutic option for patients with RA who do not have adverse prognostic factors.     

GFR in Patients with β-Thalassemia Major

Background and objectives

Patients with β-thalassemia major (TM) may have tubular dysfunction and glomerular dysfunction, primarily hyperfiltration, based on eGFR. Assessment of GFR based on serum creatinine concentration may overestimate GFR in these patients. This study sought to determine GFR by using inulin clearance and compare it with measured creatinine clearance (Ccr) and eGFR.

Design, setting, participants & measurements

Patients followed up in an Israeli thalassemia clinic who had been regularly transfused for years and treated with deferasirox were included in the study. They were studied by inulin clearance, Ccr, the CKD Epidemiology Collaboration and the Modification of Diet in Renal Disease equations for eGFR, and the Cockcroft–Gault estimation for Ccr. Expected creatinine excretion rate and tubular creatinine secretion rate were calculated.

Results

Nine white patients were studied. Results, given as medians, were as follows: serum creatinine was 0.59 mg/dl (below normal limits); GFR was low (76.6 ml/min per 1.73 m²) and reached the level of CKD; Ccr was 134.9 ml/min per 1.73 m², higher than the GFR because of a tubular creatinine secretion rate of 30.3 ml/min per 1.73 m² (this accounted for 40% of the Ccr); and eGFR calculated by the CKD Epidemiology Collaboration and Modification of Diet in Renal Disease equations and Cockcroft–Gault–estimated Ccr were 133, 141, and 168 ml/min per 1.73 m², respectively. These latter values were significantly higher than the GFR, reaching the hyperfiltration range, and indicated that the estimation techniques were clinically unacceptable as a method for measuring kidney function compared with the GFR according to Bland and Altman analyses.

Conclusions

Contrary to previous reports, patients in this study with TM had normal or reduced GFR. The estimating methods showed erroneous overestimation of GFR and were clinically unacceptable for GFR measurements in patients with TM by Bland and Altman analysis. Therefore, more accurate methods should be used for early detection of reduced GFR and prevention of its further decline toward CKD in these patients.     

Results of Coexistence of β-Thalassemia Minor in Hb H Disease Patients

Abstract

The aim of this study was to determine the hematological characteristics in a large group of Hb H (β4) patients with or without a coexisting β-thalassemia (β-thal), identified by a thalassemia screening program in mainland China. A total of 361 patients with Hb H disease were found, including 343 with deletional types and 18 with nondeletional types. β-Thalassemia was found in 28 (7.8%) out of the 361 Hb H cases, and all of the 28 cases had the deletional type of Hb H disease. Lower hemoglobin (Hb) levels were detected in cases with the nondeletional type compared to those in cases with the deletional type. β-Thalassemia significantly increases the Hb levels in Hb H cases. The Hb H and Hb Bart’s (γ4) fractions were visible in 270 (85.7%) and 122 (38.7%) out of 315 deletional type cases, respectively, while no Hb H or Hb Bart’s fractions were detectable in 28 deletional type cases with β-thal. Therefore, the diagnosis of Hb H disease in a β-thal carrier is challenging. Molecular analysis of α- and β-globin genes is imperative in all cases with a β-thal trait.     

Haplotype Analysis of Three Common β-Thalassemia Mutations in Syrian Patients

Abstract

β-Globin haplotypes were used to investigate the origin of three common β-globin mutations, IVS-I-110 (G>A); HBB: c.93-21G>A, IVS-I-1 (G>A); HBB: c.92?+?1G>A and codon 39 (C>T); HBB: c.118C?> T in Syrian patients. Haplotype analysis was done for 49 unrelated patients with β-thalassemia (β-thal) and 20 unrelated healthy subjects by polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) for the β-globin gene cluster of the following polymorphic restriction sites: HincII 5' to ε, HindIII 5' to ^Gγ, HindIII 5' to ^Aγ, HincII in ψβ, HincII 3' to ψβ, AvaII in β, and HinfI 3' to β. The IVS-I-110 mutation was associated with three haplotypes: I [+ – – – – + +] (79.4%), V [+ – – – – + –] (5.9%) and VII [+ – – – – – +] (14.7%), while, the two mutations IVS-I-1 and codon 39 were be linked to a single haplotype V (100.0%) and II [– + + – + + +] (100.0%), respectively. The normal chromosomes (β^A/β^A) were associated with four haplotypes, I (50.0%), II (7.5%), V (32.5%) and VII (10.0%). In the Syrian population, the IVS-I-110 mutation was associated with multi haplotypes, whereas the IVS-I-1 and codon 39 mutations have a single origin. More studies for the other mutations will be very useful for genetic epidemiological studies in Syria.     

Fetal Hemoglobin in the Maternal Circulation – Contribution of Fetal Red Blood Cells

The major hemoglobin (Hb) during fetal life is fetal Hb (Hb F). It is mostly replaced by adult Hbs before birth and during the first year of life. In adults, where Hb F comprises <2.0% of the total Hb, it is not homogenously distributed among the red blood cells (RBCs) but is concentrated in a few RBCs, termed F-cells. Interestingly, for reasons that are unclear, Hb F increases in the maternal circulation during pregnancy. This increased Hb F could have two potential origins that are not mutually exclusive: A) maternal origin, due to inducing environment of Hb F in the maternal erythroid precursors; B) fetal origin, due to fetal cells crossing the placenta and entering the maternal circulation. The question we present herein is whether the observed increased Hb F in the maternal circulation during pregnancy is, at least partially, derived from the fetal origin. Peripheral blood was obtained from normal neonates (1–3 days old), adult men and pregnant and non pregnant women. The RBCs were stained for Hb F and carbonic anhydrase (CA) using a fetal cell count kit and analyzed by flow cytometry. Fetal and adult F-cells were distinguished by their expression of Hb F and CA. Fetal F-cells were Hb F⁺⁺/CA^?, while adult F-cells were Hb F⁺/CA⁺. Comparing pregnant and non pregnant women samples (n?=?10), we found six samples of pregnant women with 0.2–1.7% fetal cells, but none in the non pregnant group. These results support the possibility that at least part of the increase in Hb F during pregnancy is due to fetal cells entering the maternal circulation.     

Evaluation of the Effect of Support-Training System of Peer Group on Promotion of Self-Care in β-Thalassemia Major Patients in Southern Iran

Abstract

β-Thalassemia (β-thal) is a chronic illness and its complications make the patient less compliant with the treatment protocol. This study aimed to evaluate the effect of a support-training system of peer group on promotion of self-care in β-thal major (β-TM) patients. In this semi-experimental study, 112 β-TM were randomly selected and assigned to the study and control groups. Seven β-TM patients, who were physically, mentally and socially normal, were selected and trained as the peer group. Eight training sessions over 4 months were done by the peer group. The questionnaire with 50 questions was scored using the Likert scale, always with 1 point, sometimes 0.5 point and never 0 points. In the study group, before intervention, the mean score of the patients was 29.84?±?6.16, which, after intervention, increased significantly to 37.14?±?4.35, p?<?0.001. In the control group, the overall mean self-care patients’ score decreased significantly, from 29.76?±?7.18 to 29.48?±?7.02. No significant difference was observed between pre and post intervention in the control group in all aspects of self-care (daily activities, fitness and wellness, nourishment, stress relief, job and home environment, time management, expression and creativity, support, items supporting self-care, self-care of the sickness), but it was significant in the study group. The results revealed the positive impact of peer group in promoting self-care of β-TM patients in the study group compared to the control group, which may be used as a frontline educational model in these patients.     

Flow Cytometric Analysis of Expression of Transforming Growth Factor-β and Glucocorticoid-Induced Tumor Necrosis Factor Receptor on CD4+ CD25+ T Cells of Patients with Inflammatory Bowel Disease

To determine whether human CD4+CD25+ cells express glucocorticoid-induced tumor necrosis factor receptor (GITR) and transforming growth factor-β (TGF-β) and the difference in CD4+CD25+ cells between patients with inflammatory bowel diseases and healthy subjects, peripheral blood lymphocytes were obtained from patients with ulcerative colitis (UC; n = 50), Crohn's disease (CD; n = 49), and healthy volunteers (control; n = 50) and flow cytometric analysis was performed. In control subjects, the expression of GITR on CD4+CD25+ cells (41.8 ± 10.5%) was significantly higher than on CD4+CD25– cells (11.1 ± 7.4%). Similarly, TGF-β expression on CD4+CD25+ cells (5.3 ± 4.6%) was higher than on CD4+CD25– cells (1.2 ± 1.4%). There were no significant differences among UC, CD, and control in CD4+CD25+/CD4+ ratio. However, there was a significant difference in the CD4+CD25+TGF-β+/CD4+CD25+ ratio between active UC and inactive UC (2.7 ± 2.6 and 7.2 ± 3.9%, respectively). The results suggest that TGF-β is involved in the induction or sustained remission of UC.     

Clinicopathological and Radiological Study of Egyptian β-Thalassemia Intermedia and β-Thalassemia Major Patients: Relation to Complications and Response to Therapy

The clinico epidemiological characteristics, frequency of complications, and response to various therapeutic modalities in 80 Egyptian β-thalassemia intermedia (β-TI) patients were compared with 70 β-thalassemia major (β-TM) patients. β-Thalassemia intermedia patients had a higher incidence of left atrium dilatation, right ventricular dilatation and pulmonary hypertension, whereas, β-TM patients showed a higher incidence of left ventricular (LV) dilatation, restrictive LV filling and impaired LV contractility, with an overall higher incidence of heart disease (p <0.001). Short stature, delayed puberty, osteoporosis, bone fractures, diabetes mellitus and viral hepatitis was frequently observed in β-TM patients compared with β-TI patients (p <0.05). Administration of hydroxyurea (HU) alone was associated with significant improvement in hematological parameters and quality of life for β-TI patients. In conclusion, the risk of complications still burdens the life of Egyptian thalassemia patients and their frequency varies between β-TI and β-TM. We provide evidence that calls for the use of HU in β-TI patients.     

Priapism,an Emerging Complication in β-Thalassemia Intermedia Patients

The increase in survival rate of β-thalassemia (β-thal) patients allowed for the appearance and manifestation of several complications in almost every organ system. Priapism in β-thal patients is rarely reported in the literature. We herein report and investigate the occurrence of two cases of priapism in two young patients with β-thal intermedia (β-TI). The potential mechanisms are due to either a cellular mechanism involving a thrombus obstructing the efferent venules of the corpora cavernosa leading to priapism, or a recently elucidated functional mechanism that causes alteration of nitric oxide (NO) response of the penis, ultimately causing priapism. This should incite clinicians for a close follow-up and monitoring of high risk patients who are susceptible to developing priapism.     

Oxidative Status and Plasma Lipid Profile in β-Thalassemia Patients

Abstract

β-Thalassemia (β-thal) is a genetic disorder, representing a major health problem in Algeria. It is associated with altered lipid levels and a state of oxidative stress that can lead to cardiac complications and premature death. We examined the plasma lipid profile and redox status of 46 patients with β-thal major (β-TM) and β-thal intermedia (β-TI) compared to 36 healthy subjects. Plasma lipids including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were investigated. Oxidative status was evaluated by measuring malondialdehyde (MDA), reduced glutathione (GSH) and catalase (CAT) activity. The potential relationships between these parameters and the hemoglobin (Hb) blood concentrations, serum ferritin, duration and frequency of transfusion, splenectomy as well as age, were examined. Our data indicated that the study patients were under increased state of oxidative stress associated with hypertriglyceridemia, and hypocholesterolemia. The CAT activity was negatively correlated with Hb concentration and LDL-C/TG ratio and positively with years of transfusion. The elevated TC/HDL-C ratio particularly in β-TM patients who were younger, correlated positively with ferritinemia and triglyceride levels and suggested an increased coronary risk. This heightened risk state should lead to the inclusion of this index (TC/HDL-C) in clinical management, particularly in splenectomized patients.     

Evaluating the Safety and Efficacy of Silymarin in β-Thalassemia Patients: A Review

Abstract

β-Thalassemia (β-thal) is a type of hereditary anemia affecting hemoglobin (Hb) synthesis causing severe chronic anemia in homozygous patients. Regular blood transfusions are the mainstay treatment for this type of anemia. In turn, this leads to iron overload which is responsible for the formation of reactive oxygen species (ROS), oxidative stress and organ damage. Deferoxamine (DFO) is the standard of treatment for iron overload but regular painful subcutaneous administration of this medication prevents optimal compliance. Oral chelators, such as deferasirox (DFX) and deferiprone (DFP), are also effective and safe. Deferiprone is most effective in combination therapy with DFO rather than monotherapy; however, DFX is very expensive and the cost is a significant new burden for patients. Recently, researchers have proposed an iron chelating effect for silymarin that is a flavonoid extract from the milk thistle plant. This extract has different properties and has long been used for its antioxidant and hepatoprotective effects. In this review we assess different aspects of silymarin’s potential effects and compare them to the profile of thalassemic patients.     

The Frequency of HBB Mutations Among β-Thalassemia Patients in Hamadan Province,Iran

β-Thalassemia (β-thal) caused by mutations on the HBB gene is the most common single-gene disorder in the world. In this study, the HBB gene mutation was investigated in Hamadan province, Iran. Forty-one patients referred to a referral hospital were admitted to the study. DNA samples were extracted from peripheral blood. The HBB gene was sequenced in all recruited patients. Eleven mutations and eight polymorphisms were found in the studied patients. IVS-II-1 (G>A) (HBB: c.315+1?G>A) was the most common mutation, accounting for 25.61% of mutant alleles. Other mutations included codon 8 (–AA) (HBB: c.25?26delAA); IVS-I-110 (G>A) (HBB: c.93?21?G>A); codons 8/9 (+G) (HBB: c.27?28insG); IVS-I-1 (G>A) (HBB: c.92?G>A); codon 44 (–C) (HBB: c.135delC); codons 25/26 (+T) (HBB: c.78?79insT); IVS-I-130 (G>C) (HBB: c.93?1?G>C); –28 (A>C) (HBB: c.?78 A>C); codons 36/37 (–T) (HBB: c.112delT) and IVS-I-6 (T>C) (HBB: c.92+6 T>C). According to our findings, the IVS-II-1 mutation has the highest prevalence in Hamadan Province. It was found that the total frequency of the IVS-II-1, codons 25/26 (+T), codons 8/9 (+G), IVS-I-110 and IVS-I-1 mutations was 82.92%. Therefore, given these findings, it is recommended that these five mutations are screened for as a first step in laboratories without sequencing instruments, and that the rest of the gene is subsequently examined.