Longitudinal study of glomerular hyperfiltration and normalization of estimated glomerular filtration in adults with sickle cell disease.

Glomerular hyperfiltration is common in sickle cell disease (SCD) and precedes proteinuria and declining kidney function. We evaluated hyperfiltration in SCD patients and its "normalization." Routine visit data were collected retrospectively from adult SCD patients in a single centre from 2004 to 2013. Baseline was defined as first available serum creatinine and hyperfiltration as estimated glomerular filtration rates (eGFR) >130 ml/min/1·73 m2 for women and >140 ml/min/1·73 m2 for men. Normalization of hyperfiltration was eGFR reduction to 90-130 ml/min/1·73 m2 for women or 90-140 ml/min/1·73 m2 for men. Among 292 patients, median age was 27 years [interquartile range (IQR):20·0-38·0], and 56·8% had baseline hyperfiltration. Baseline hyperfiltration was inversely associated with age [odds ratio (OR):0·86, 95% confidence interval (CI): 0·82-0·90; P < 0·0001], male sex (OR:0·16, 95% CI: 0·07-0·41; P = 0·0001), haemoglobin (OR:0·76, 95% CI 0·61-0·94; P = 0·01), weight (OR:0·96, 95% CI: 0·93-0·99; P = 0·004), and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACE-I/ARB) use (OR:0·08, 95% CI: 0·01-0·75; P = 0·03), and positively with hydroxycarbamide use (OR:2·99, 95% CI: 1·18-7·56; P = 0·02). Of 89 hyperfiltration patients without baseline proteinuria, 10 (11·2%) developed new-onset proteinuria [median 1·05 years (IQR:0·63-2·09)]. Normalization of hyperfiltration was less likely with higher baseline eGFR [hazard ratio (HR):0·90, 95% CI: 0·86-0·95; P < 0·0001] and more likely in males (HR:6·35, 95% CI:2·71-14·86, <0·0001). Hyperfiltration is common in adult SCD patients, particularly when younger. Decline to normal values is more likely in males, possibly representing kidney function loss rather than improvement in hyperfiltration.

SLN124, a GalNac-siRNA targeting transmembrane serine protease 6, in combination with deferiprone therapy reduces ineffective erythropoiesis and hepatic iron-overload in a mouse model of ß-thalassaemia.

Beta-thalassaemia is an inherited blood disorder characterised by ineffective erythropoiesis and anaemia. Consequently, hepcidin expression is reduced resulting in increased iron absorption and primary iron overload. Hepcidin is under the negative control of transmembrane serine protease 6 (TMPRSS6) via cleavage of haemojuvelin (HJV), a co-receptor for the bone morphogenetic protein (BMP)-mothers against decapentaplegic homologue (SMAD) signalling pathway. Considering the central role of the TMPRSS6/HJV/hepcidin axis in iron homeostasis, the inhibition of TMPRSS6 expression represents a promising therapeutic strategy to increase hepcidin production and ameliorate anaemia and iron overload in ß-thalassaemia. In the present study, we investigated a small interfering RNA (siRNA) conjugate optimised for hepatic targeting of Tmprss6 (SLN124) in ß-thalassaemia mice (Hbbth3/+ ). Two subcutaneous injections of SLN124 (3 mg/kg) were sufficient to normalise hepcidin expression and reduce anaemia. We also observed a significant improvement in erythroid maturation, which was associated with a significant reduction in splenomegaly. Treatment with the iron chelator, deferiprone (DFP), did not impact any of the erythroid parameters. However, the combination of SLN124 with DFP was more effective in reducing hepatic iron overload than either treatment alone. Collectively, we show that the combination therapy can ameliorate several disease symptoms associated with chronic anaemia and iron overload, and therefore represents a promising pharmacological modality for the treatment of ß-thalassaemia and related disorders.

Digital thermography and vascular involvement in ß-thalassemia intermedia.

Beta-thalassemia intermedia (ß-TI) is associated with vascular dysfunction. We used digital thermal monitoring (DTM), a non-invasive tool that evaluates vascular function based on changes in fingertip temperature during and after cuff occlusion on ß-TI patients. Thirty-three patients (18 years and older) were recruited in this study and divided into 3 groups: thalassemia, anemic controls, and healthy controls. Exclusion criteria included factors that are known to be associated with vascular damage. Patients underwent DTM and results were extracted as vascular reactivity index (VRI), a measure of how well the circulatory system responds to stimuli that require adjustments of blood flow. One-way analysis of variance (ANOVA) was used to test the mean difference in VRI between the 3 groups. A multiple linear regression was also carried out with VRI as the outcome of interest and a function of covariates that were thought to be of clinical relevance to VRI. The frequency, mean VRI ± standard error (SE) for the thalassemic group were (N = 16), mean = 2.243 ± 0.111; for anemic controls (N = 9), mean = 2.374 ± 0.162; and for the controls (N = 8), mean = 2.338 ± 0.092. ANOVA test indicated a non-significant difference in mean VRI between the three groups (P value = 0.731). Multiple linear regression couldn't detect any significant association between VRI and any of the predictors including the groups. Our study did not show a significant difference in VRI between the 3 study groups. Prospective studies of larger sample size are warranted to establish DTM as a possible non-invasive tool used to evaluate vascular function in ß-TI patients.

Erythrocyte transfusion restored heart rate variability in children with thalassemia major.

Thalassemia major (TM) is a severe transfusion-dependent anemia. Regular erytrocyte transfusion is required for the treatment of thalassemia patients. However, repeated transfusion may result in impairements in heart function. In this study, we aimed to investigate short-term effects of erythrocyte transfusion on autonomic control of heart in children with thalassemia major. For that purpose heart rate variability (HRV), which is a non-invasive method used to evaluate the effects of the autonomic nervous system on the heart rhythym, was measured before and after erythrocyte transfusion and compared to the healthy controls. Children diagnosed with TM (n = 17) and sex and age matched healthy children (HC, n = 30) were included in the study. HRV values of TM patients were measured 5 min before erythrocyte transfusion (BET, n = 17) and 5 min after erythrocyte transfusion (AET, n = 17). Parameters of time-domain and frequency-domain of HRV were evaluated in all participants. Heart rate (HR) was higher in the BET than AET (P = 0.002) but there was no difference between AET and HC groups (P > 0.05). HRV parameters were lower in BET than AET (P < 0.05) but there were no statistical difference between AET and HC (P> 0.05). The data suggest that, in thalassemia major patients, erythrocyte transfusion restores HR and HRV parameters to the levels observed in healthy controls and, thus, in short-terms, appears to be beneficial for the autonomic control of the heart.

Renal function in ß-thalassemia major patients treated with two different iron-chelation regimes.

BACKGROUND: Renal injury in transfusion dependent ß thalassemia patients (TDT) has been attributed to iron overload, chronic anemia and iron-chelation therapy (ICT) toxicity. We studied renal function in TDT patients treated with two different ICT regimes. PATIENTS AND METHODS: We studied 36 TDT patients: 26 received deferasirox (DFX) and 10 were treated with deferoxamine (DFO) +/- deferiprone (DFP). RESULTS: Increased uNAG was found in 30% of the DFX group vs. 10% of the DFO+/-DFP group, the mean uNAG level in the DFX group was significantly higher than in the DFO+/-DFP group, (P < 0.05). A moderate negative correlation was found between uNAG levels and mean serum ferritin for the prior 10 years (P = 0.03), more pronounced for the DFO+/-DFP group. Twenty nine patients had had their renal function evaluated 10 years earlier; eGFR significantly declined in patients switched to DFX (P = 0.0093) but not in patients who continued DFO+/-DFP. CONCLUSIONS: A high prevalence of renal tubular damage was observed in our TDT patients, particularly those treated with DFX; uNAG was negatively associated with mean 10-year serum ferritin, suggesting ICT's involvement in tubular injury. A significant decline in eGFR compared to a decade earlier was observed only in patients currently treated with DFX. Strict follow-up of renal function in TDT patients is warranted.

ß-Thalassemia minor & renal tubular dysfunction: is there any association?

OBJECTIVE: Beta(ß)-thalassemia is one of the most common hereditary hematologic disorders. Patients with thalassemia minor (TM) are often asymptomatic and the rate of renal dysfunction is unknown in these patients. Due to the high prevalence of renal dysfunction in Iran, the current study aimed to determine renal tubular dysfunction in patients with beta-TM. METHODS: In this case-control study, 40 patients with TM and 20 healthy subjects were enrolled and urinary and blood biochemical analysis was done on their samples. Renal tubular function indices were determined and compared in both groups. Data was analyzed by SPSS software, version 20.0. RESULTS: The fraction excretion (FE) of uric acid was 8.31 ± 3.98% in the case and 6.2 ± 34.71% in the control group (p = 0.048). Also, FE of potassium was significantly higher in patients with TM (3.22 ± 3.13 vs. 1.91 ± 0.81; p = 0.036). The mean Plasma NGAL level was 133.78 ± 120.28 ng/mL in patients with thalassemia and 84.55 ± 45.50 ng/mL in the control group (p = 0.083). At least one parameter of tubular dysfunction was found in 45% of patients with thalassemia. CONCLUSION: Based on the results of this study, the prevalence of tubular dysfunction in beta-thalassemia minor patients is high. Due to the lack of knowledge of patients about this disorder, periodic evaluation of renal function in TM patients can prevent renal failure by early diagnosis.

Ineffective Erythropoiesis in ß-Thalassaemia: Key Steps and Therapeutic Options by Drugs.

ß-thalassaemia is a rare genetic condition caused by mutations in the ß-globin gene that result in severe iron-loading anaemia, maintained by a detrimental state of ineffective erythropoiesis (IE). The role of multiple mechanisms involved in the pathophysiology of the disease has been recently unravelled. The unbalanced production of α-globin is a major source of oxidative stress and membrane damage in red blood cells (RBC). In addition, IE is tightly linked to iron metabolism dysregulation, and the relevance of new players of this pathway, i.e., hepcidin, erythroferrone, matriptase-2, among others, has emerged. Advances have been made in understanding the balance between proliferation and maturation of erythroid precursors and the role of specific factors in this process, such as members of the TGF-ß superfamily, and their downstream effectors, or the transcription factor GATA1. The increasing understanding of IE allowed for the development of a broad set of potential therapeutic options beyond the current standard of care. Many candidates of disease-modifying drugs are currently under clinical investigation, targeting the regulation of iron metabolism, the production of foetal haemoglobin, the maturation process, or the energetic balance and membrane stability of RBC. Overall, they provide tools and evidence for multiple and synergistic approaches that are effectively moving clinical research in ß-thalassaemia from bench to bedside.

[Research progress of iron metabolism in phenotype modification of ß-thalassemia].

ß-thalassemia is a type of inherited hemolytic anemia caused by decreased globin production due to defect of the HBB gene. The pathogenesis of the disease is imbalance of α/ß globin chains. The excess of α-globin chains will form hemichromes which can damage red blood cell membranes and lead to hemolysis, ineffective erythropoiesis, and secondary iron overload. Iron overload in turn can cause complications such as growth retardation, liver cirrhosis, cardiac insufficiency, and aggravate the disease phenotype. In recent decades, genes participating in iron metabolism have been discovered, and the mechanism of iron metabolism in the development of thalassemia has gradually been elucidated. Subsequently, by manipulating the expression of key genes in iron metabolism such as hepcidin and transferrin receptor, researchers have revealed that iron restriction can improve ineffective hematopoiesis and iron overload, which may provide a potential approach for the treatment of thalassemia. This article reviews the progress of research on iron metabolism-related genes and related pathways in ß-thalassemia.

Emerging therapies in ß-thalassemia: toward a new era in management.

INTRODUCTION: The thalassemias are among the most  common inherited monogenic diseases worldwide, characterized by autosomal recessive inherited defects in the production of hemoglobin. Currently available conventional therapies have many challenges and limitations. Advances in understanding the underlying pathophysiology of ß-thalassemia enabled clinicians and researchers to move toward the development of novel therapeutic modalities. These can be classified into three categories based on their efforts to address different features of the underlying pathophysiology of ß-thalassemia: correction of the globin chain imbalance, addressing ineffective erythropoiesis, and improving iron overload. AREAS COVERED: In this review, we will provide an overview of the novel therapeutic approaches that are currently in development for ß-thalassemia. EXPERT OPINION: A thorough understanding of the pathophysiology and overall disease burden of ß-thalassemia has aided clinicians and scientists to optimize disease management approaches and construct a plan for the development of novel therapies, with ultimate goals of prolonging longevity, reducing symptom burden, improving compliance and adherence for a better quality of life.

A computational model to understand mouse iron physiology and disease.

It is well known that iron is an essential element for life but is toxic when in excess or in certain forms. Accordingly there are many diseases that result directly from either lack or excess of iron. Yet many molecular and physiological aspects of iron regulation have only been discovered recently and others are still elusive. There is still no good quantitative and dynamic description of iron absorption, distribution, storage and mobilization that agrees with the wide array of phenotypes presented in several iron-related diseases. The present work addresses this issue by developing a mathematical model of iron distribution in mice calibrated with ferrokinetic data and subsequently validated against data from mouse models of iron disorders, such as hemochromatosis, ß-thalassemia, atransferrinemia and anemia of inflammation. To adequately fit the ferrokinetic data required inclusion of the following mechanisms: a) transferrin-mediated iron delivery to tissues, b) induction of hepcidin by transferrin-bound iron, c) ferroportin-dependent iron export regulated by hepcidin, d) erythropoietin regulation of erythropoiesis, and e) liver uptake of NTBI. The utility of the model to simulate disease interventions was demonstrated by using it to investigate the outcome of different schedules of transferrin treatment in ß-thalassemia.

Cardiac Iron Overload by MRI in Children With B-Thalassemia Major and its Correlation With Cardiac Function by Echocardiography.

BACKGROUND: Serial echocardiography is strongly recommended in asymptomatic B-thalassemia major (TM) patients for early detection of subtle cardiac dysfunction. T2*magnetic resonance imaging (MRI) is a noninvasive measurement of myocardial iron burden. Yet, it is not always available in many centers. Our study aimed to evaluate the myocardial function in TM patients using different echocardiographic modalities and to correlate these findings with cardiac T2*MRI. PATIENTS AND METHODS: This is a cross-sectional study that was carried out on 140 children with a mean age of 10.9±3.7 years. One hundred children with TM and 40 healthy children were matched for age and sex as a control group. Serum ferritin, serum iron, and iron-binding capacity were measured. Cardiac iron overload was assessed by T2*MRI and cardiac function was assessed by echocardiography. The local ethics committee approved the study. RESULTS: Among 100 children with TM, only 32% had cardiac iron overload of 8.525±5.45 detected by cardiac T2*MRI. Iron deposition correlated significantly with age. Markers of iron overload were significantly correlated with cardiac T2*MRI. There were significantly lower values of myocardial performance index, longitudinal strain, circumferential strain, area strain, and radial strain in TM patients compared with the controls (P<0.001). Only the myocardial performance index was correlated with T2*MRI. CONCLUSIONS: This study confirms that some parameters measured by tissue Doppler imaging such as the myocardial performance index could be useful for the early detection of cardiac impairment in asymptomatic TM patients when cardiac MRI is lacking. Further studies on a large scale to identify other parameters with high sensitivity are recommended.

HbA1C as a marker of retrograde glycaemic control in diabetes patient with co-existed beta-thalassaemia: A case report and a literature review.

WHAT IS KNOWN AND OBJECTIVE: The HbA1C marker used in assessing diabetes control quality is not sufficient in diabetes patients with thalassaemia. CASE DESCRIPTION: A male diabetic patient with thalassaemia was hospitalized due to distal neuropathic pain, right toe trophic ulcer, unacceptable five-point glycaemic profile and recommended HbA1C value. After simultaneously initiated insulin therapy and management of ulcer by hyperbaric oxygen, the patient showed improved glycaemic control and ulcer healing, which led to the patient's discharge. WHAT IS NEW AND CONCLUSION: In thalassaemia and haemoglobinopathies, due to discrepancies in the five-point glycaemic profile and HbA1C values, it is necessary to measure HbA1C with a different method or to determine HbA1C and fructosamine simultaneously.

Headache: an important symptom possibly linked to white matter lesions in thalassaemia.

Neurological manifestations are reported only occasionally in patients with thalassaemia and are given much less prominence than the complications related to anaemia and iron overload. White matter changes (WMCs) on magnetic resonance imaging (MRI) in patients with thalassaemia were first reported two decades ago but the significance of these lesions remains unclear. We studied the neurological and cognitive manifestations in 82 older patients with thalssaemia [25 Thalassaemia major (TM), 24 thalassaemia intermedia (TI) and 33 haemaglobin E ß thalassaemia (EBT)] and 80 controls, and found that headaches were more common in thalassaemia patients (50/82, 61%) than in controls (18/80, 22·5%: P < 0·001). WMCs on MRI were found in 20/82 (24·3%) patients and 2/29 (6·9%) controls had (P = 0·078). WMC were more common among those with headaches (17/50: 34%) than in those without headache (3/32; 9·3%) (P = 0·023). WMCs were not associated with reduction of cognition. Nevertheless, cognition was lower in the TI and EBT groups compared with those with TM (P = 0·002). The association of headache with WMC in thalassaemia has not been reported before and warrants further study.

Long-term improvement in cardiac magnetic resonance in ß-thalassemia major patients treated with deferasirox extends to patients with abnormal baseline cardiac function.

The management of iron overload in thalassemia has changed dramatically since the implementation of magnetic resonance imaging, which allows detection of preclinical iron overload and prevention of clinical complications. This study evaluated the effect of deferasirox (DFX), the newest once-daily oral chelator, on cardiac function, iron overload and cardiovascular events over a longer follow up in a "real world" setting. Longitudinal changes in cardiac magnetic resonance T2*, cardiac function parameters and cardiovascular clinical events were assessed in a cohort of 98 TM patients exposed to DFX for a mean of 6.9 years (range 1.8-11.6 years). No cardiac death or incident heart failure occurred. Cardiac T2* significantly increased (+2.6 ± 11.9 msec; P = 0.035) in the whole population, with a significantly greater increase (+11.6 ± 15.5 msec, P = 0.019) in patients with cardiac iron overload (T2* <20 ms). A significant improvement in left-ventricular ejection fraction (LVEF) (from 50.6 ± 6 to 60.2 ± 5; P = 0.001) was observed in 11 (84.6%) out of 13 patients who normalized cardiac function (LVEF >56%). Arrhythmias were the most frequent cardiac adverse event noted but none led to DFX discontinuation. Our data indicate that DFX is effective in maintaining cardiac iron level in the normal range and in improving cardiac iron overload. No heart failure or cardiac death was reported over this longer observation up to 12 years. For the first time, a DFX-induced improvement in LVEF was observed in a subgroup of patients with abnormal cardiac function at baseline, a preliminary observation which deserves further evaluation.

Elevated tricuspid regurgitation velocity in congenital hemolytic anemias: Prevalence and laboratory correlates.

Elevated tricuspid valve regurgitation jet velocity (TRV ≥ 2.5 m/s) is associated with mortality among adults with sickle cell disease (SCD), but correlative biomarkers are not studied according to treatment exposure or genotypes. To investigate the associations between biomarkers and TRV elevation, we examined the relationship between TRV and hemolytic, inflammatory, and cardiac biomarkers, stratified by disease-modifying treatments and SCD genotype. In total, 294 participants with SCD (mean age, 11.0 ± 3.7 years) and 49 hereditary spherocytosis (HS; mean age, 22.9 ± 19.75 years) were included for comparison and enrolled. TRV was elevated in 30.7% of children with SCD overall: 18.8% in HbSC/HbSß+ -thalassemia, 28.9% in untreated HbSS/HbSß0 -thalassemia, 34.2% in HbSS/HbSß0 -thalassemia hydroxyurea-treated, and 57% in HbSS/HbSß0 -thalassemia chronic transfusion treated. TRV was elevated in 10.7% and 27.8% in HS children and adults, respectively. In children with SCD, elevated TRV was correlated with hemoglobin (odds ratio [OR] = 0.78, P = 0.004), lactate dehydrogenase (LDH; OR = 2.52, P = 0.005), and N-terminal pro-brain natriuretic peptide (NT-pro BNP; OR = 1.003, P = 0.004). In multivariable logistic regression, adjusting for genotype, sex, hemolytic index, and treatment, hemoglobin concentration remained the only significant variable associated with elevated TRV in untreated HbSS/HbSß0 -thalassemia participants. TRV was not associated with inflammatory markers, other markers of hemolysis, or NT-pro BNP in untreated HbSS/HbSß0 -thalassemia. Neither hemoglobin nor LDH was associated with TRV in HbSC/HbSß+ -thalassemia. These results suggest that elevated TRV is influenced by the degree of anemia, possibly reflecting sickling as part of the disease pathophysiology. Prospective studies should monitor hemoglobin concentration as children with SCD age into adulthood, prompting initiation of TRV screening and monitoring.

Pulmonary functions in Egyptian children with transfusion-dependent ß-thalassemia.

BACKGROUND: In ß-thalassemia, there are varying degrees of ineffective haematopoiesis, intermittent haemolysis and iron overload. Excess iron is deposited in organs such as the heart, the liver, the endocrine glands and the lungs. OBJECTIVES: To evaluate the pulmonary functions in asymptomatic beta thalassemic children on regular transfusion therapy and their relation to iron overload. METHODS: The study included 50 transfusion-dependent ß-thalassemic children and 50 apparently healthy children as control. All children had undergone pulmonary function tests (spirometry, lung volumes and diffusion capacities). In addition, test to determine the mean serum ferritin of the last 2 years and pre-transfusion haemoglobin and chest radiograph and echocardiography were performed for the thalassemic children only. RESULTS: A total of 70% of the thalassemic children had diffusion impairment, whereas 34% of them had associated restrictive abnormality. Thalassemic children with serum ferritin >2500 ng mL-1 had significantly lower values of forced vital capacity (FVC), forced expiratory volume at one second (FEV1), peak expiratory flow (PEFR), total lung capacity (TLC) and diffusing capacity of carbon monoxide (DLCO) (P < 0·05). Only diffusion impairment had a significant positive correlation with serum ferritin level. Restrictive impairment had significant positive correlations with age, duration of blood transfusion and serum ferritin level and a significant negative correlation with duration of chelation (P < 0·05). Having a serum ferritin >2500 ng mL-1 was the only predicting factor for diffusion impairment and the strongest predicting factor for restrictive dysfunction. CONCLUSION: Despite being asymptomatic, the majority of thalassemic children in this study suffered from diffusion impairment either alone or in combination with restrictive dysfunction. These pulmonary dysfunctions correlated significantly with body iron stores measured by serum ferritin.

Insulin secretion-sensitivity index-2 could be a novel marker in the identification of the role of pancreatic iron deposition on beta-cell function in thalassemia major.

The purpose of this study is to evaluate the impact of insulin secretion-sensitivity index-2 (ISSI-2) in the identification of the role of pancreatic iron deposition on beta-cell function in thalassemia major. Tissue iron stores were measured with magnetic resonance imaging (MRI) in the liver (R2), pancreas (R2*), and heart (T2*). ISSI-2 was assessed as a novel oral glucose tolerance test-based measure of beta-cell function. Also, the Stumvoll index showing the insulin sensitivity and Stumvoll index estimating first and second phase insulin secretion were calculated. Fourteen of the 51 Thalassemia Major patients, aged 8-34 (mean 21.1 ± 7.2) years-old, had either an impaired glucose tolerance test (n = 9, 17.6%) or diabetes mellitus (n = 5, 9.8%)-referred to as the glucose dysregulation (GD) group. The median serum ferritin and the mean liver R2 and cardiac T2* values were not significantly different between the GD and normal glucose tolerance (NGT, n = 37) groups whereas pancreas R2* was significantly higher in the GD group compared to the NGT group (p = 0.004). Patients with GD showed significantly lower ISSI-2 index (p < 0.001) as well as the Stumvoll index and Stumvoll first and second phase indices compared to those with NGT (p < 0.001). All patients with GD displayed a pancreas R2* >50 Hz and ISSI-2 <2. In conclusion, Pancreas R2* MRI combined with ISSI-2 index may be valuable parameters to identify patients at the highest risk for developing glucose dysregulation.

Left and Right Atrial Function and Remodeling in Beta-Thalassaemia Major.

This study aimed to assess left (LA) and right atrial (RA) function in patients with beta-thalassaemia major. Thirty-eight patients (19 males) aged 34.5 ± 10.7 years and 43 (18 males) controls aged 30.3 ± 12.6 years (p = 0.12) were studied. The maximum RA and LA areas were measured using two-dimensional planimetry, while atrial and ventricular strain and strain rates were quantified using speckle-tracking echocardiography. Compared with controls, patients had significantly reduced LA and RA peak positive strain and total strain, and LA strain rate during ventricular systole and at atrial contraction (all p < 0.05). The LA and RA strain parameters were significantly associated (all p < 0.05). The maximum LA (10.2 ± 1.6 cm2/m2 vs. 8.6 ± 1.3 cm2/m2, p < 0.001) and RA (9.2 ± 1.2 cm2/m2 vs. 7.5 ± 1.3 cm2/m2, p < 0.001) areas were significantly greater in patients than controls. The LV and RV strain and early strain rates were similar between patients and controls (all p > 0.05). Four patients with significant myocardial iron overload had larger LA area (p < 0.001) than those without. Functional and structural remodeling of both the right and left atria occurs in patients with beta-thalassaemia major, even in the absence of ventricular diastolic dysfunction.

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

A retrospective evaluation of growth in 112 patients (68 males, 44 females) with Hb E (HBB: c.79G>A)/ß-thalassemia (ß-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.