Psychosocial implications of Thalassemia Major

BACKGROUND: Many causes including the chronicity of disease, burden of treatment modalities, morbidities, and the expectation of early death resulting from the disease complications, may lead to psychosocial burden in Thalassemia Major (TM) patients. METHODS: A total of 38 patients with TM and their mothers were recruited to evaluate the psychosocial burden as well as to disclose whether the psychological status of the patients contribute to the compliance with the therapy or to the contrary. Demographic and disease variables were obtained. Child Behavior Check-list (CBCL) was completed by the mothers of the patients. A detailed psychiatric interview based on the 4th edition of the Diagnostic and Statistical Manual diagnostic criteria was performed for each patient. Symptom Distress Checklist 90 (SCL-90) scale was given to all mothers for evaluating their psychopathology. RESULTS: Although CBCL scores remained between the normal ranges, desferrioxamine mesylate (DFO)-compliant patients and the patients with lower ferritin values had significantly higher scores. A total of 24% of the patients had a psychiatric diagnosis including major depression, anxiety disorder, tic disorder, and enuresis nocturnal. The psychiatric diagnosis was significantly higher in the patients who were compliant with desferrioxamine compared with the non-compliant group (P = 0.007). The SCL-90 scores indicated that the mothers who had a child with good adherence to DFO had higher scale scores than the mothers with a poor adherent child. CONCLUSIONS: The increase risk of psychosocial and behavioral problems in thalassemics and their parents indicated the importance of a lifelong psychosocial support for the prevention of mental health issues. The patients and their parents, who were more conscious of the illness, were more worried but more compliant with the therapy and need stronger psychiatric support.     

Effect of blood transfusions on oxidative stress in preterm infants

OBJECTIVE: To confirm the increase in non-transferrin bound iron (NTBI) after packed red cell (PRC) transfusion and to evaluate the association with increased oxidative stress in preterm infants. METHOD: Twenty healthy preterm infants (gestational age 28.2 (2.2) weeks; birth weight 1047 (230) g), who required blood transfusion for anaemia of prematurity were prospectively studied. Serum concentrations of NTBI, total hydroperoxides (TH), and protein SH groups, and plasma total radical trapping antioxidant capability (TAC) were measured within three hours before and after PRC transfusion. The infants were transfused with 38.6 (23) ml PRCs over 5.8 (1.0) hours, at a mean age of 43.3 (25.1) days. RESULTS: After PRC transfusion, haemoglobin concentration increased from 9.2 (1.1) to 14.6 (1.5) g/l. Mean plasma NTBI concentration after transfusion was significantly higher (0.43 (0.45) v 2.03 (1.31) micromol/l; p = 0.001), while plasma concentrations of TH (212.3 (42.2) v 214.7 (66.3) Carr units/l) and protein SH groups (317.5 (38.8) v 353.8 (57.4) micromol/), and TAC (256.3 (36.1) v 267.1 (42.4) micromol HClO/ml) remained unchanged. CONCLUSION: For three hours after PRC transfusion, plasma NTBI is significantly increased in preterm infants, but this is not associated with significant changes in oxidative stress.     

Effect of blood transfusions on cerebral haemodynamics in preterm infants

Aim: To assess the possible cerebral haemodynamic changes occurring in preterm infants after blood transfusions. Methods: Preterm infants who had undergone blood transfusions were prospectively studied using both near infrared spectroscopy and cerebral Doppler ultrasonography. Results: Fourteen infants (mean gestational age 29.6 wk, SD 2.6; mean birthweight 1430 g, SD 332) were studied at the mean age of 29 (SD 14) d. A significant increase in oxygenated haemoglobin (O 2 Hb), deoxygenated haemoglobin (HHb), mixed cerebral oxygen saturation (SmO 2 ) and change in cerebral blood volume occurred after transfusion. Between ultrasound parameters, we found a decrease in diastolic velocity and an increase in resistance index.

Conclusion: Blood transfusions improve cerebral oxygen supply and induce a decrease in cerebral blood volume, probably due to an increase in cerebral vessel resistance.     

Effect of Using Bedside Leukocyte Filter on Pulmonary Functions in Patients with Thalassemia Major

In settings of limited health resources, using leukocyte-filtered blood is limited to patients with leukocyte-mediated complications. The aim of this study was to determine the patterns of lung dysfunction among patients with β-thalassemia major (BTM) after the application of the leukostop filter during transfusion for a period of 6 months. The study included 30 patients with transfusion-dependent BTM divided into two groups according to the use of leukocyte filter. Group I included 15 patients with BTM allocated to use the leukocyte filter before each blood transfusion for 6 months and group II included 15 patients with BTM using nonleukocyte-filtered blood. Patients with history of airway disease and smokers were excluded. Chest X-ray and pulmonary function tests (PFT) using spirometry were done for each patient at baseline and after the use of the leukocyte filter for 6 months. No significant difference was found at baseline PFTs in both groups, the distribution of obstructive pulmonary disease significantly improved in group I in the postfilter evaluation, P < 0.05, however no change in pulmonary disease distribution in group II. A statistical significance improvement in forced vital capacity (FVC), forced expiratory volume in 1st second (FEV1) and FEV1/FVC in postfilter evaluation, while in group II a decline in FEV1, FVC, and no significant change in FEV1/FVC ratio. There was no correlation between serum ferritin and PFT results. Conclusion: Pulmonary function abnormalities, although subclinical is not an infrequent finding in patients with BTM; leukofiltred blood may improve PFT.     

Heart Rate Variability in Patients with Thalassemia Major

Cardiac dysfunction, including congestive heart failure and fatal arrhythmia, is a frequent cause of death among children with thalassemia major (TM). Autonomic nervous system activity typically is measured by a series of cardiovascular autonomic function tests, but these tests are unsuitable for young patients because they are invasive or complex. Heart rate variability assessment is a technique that measures the beat-to-beat variability in R-R intervals. This variability reflects changes in autonomic activity and their impact on cardiovascular function. This study examined 32 patients with TM to evaluate heart rate variability (HRV) in a preclinical phase of cardiac involvement. The study patients showed no evidence of heart failure or signs of peripheral or autonomic neuropathy. All HRV parameters were significantly reduced in the TM patient group compared with the control group. The results of this study can be interpreted as evidence of early cardiac autonomic neuropathy in young thalassemic patients. Therefore, all TM patients should be screened using HRV analysis for that complication.     

Major Causes of Hospital Admission in Beta Thalassemia Major Patients in Southern Iran

Objective

Beta thalassemia major is a prevalent hereditary disease in Mediterranean region especially Iran. Early blood transfusion is necessary for most of the patients and frequent transfusion can cause various medical problems for the patients. The aim of this study was to find major causes of hospital admission in beta thalassemia major patients to reach the accurate preventive and therapeutic plans for these patients.

Methods

Four hundred twenty six patients were admitted to the Nemazee Hospital (the main University referral Hospital Center affiliated to Shiraz University of Medical Sciences in Fars Province, southern Iran) during 3 years period (January 2007 to January 2010). A questionnaire was filled containing age, gender, hemoglobin level, frequency of blood transfusions, deferoxamine injection, cause of hospital admission and hospital course.

Findings

The mean age of patients was 11.28 years. The mean serum ferritin level was 1820±749 µg/lit. Two hundred fifty five (59.75%) patients were male and 171 (40.25%) patients were female. The top five most prevalent causes of hospital admission were splenectomy (21.8%), infections (19.9%), congestive heart failure (19.0%), diabetes mellitus (13.4%), and Liver biopsy (11.5%). (P=0.0002)

Conclusion

Results of this study revealed that infections and complications due to iron overload are major causes of hospital admission in beta thalassemia major patients.     

Neurosecretory Dysfunction of Growth Hormone Secretion in Thalassemia Major

ABSTRACT. The growth retardation of children with thalassemia major is multifactorial. Along the endocrine axis of growth hormone (GH), serum somatomedin has been shown to be deficient and GH response to GH-relasing hormone impaired, while GH response to provocative stimuli is normal. We studied the spontaneous secretion of GH in seven patients with thalassemia major and growth retardation. Three of the patients were hypothyroid, and the other four were euthyroid. Spontaneous secretion of GH in all seven patients was subnormal: the number of pulses, the mean pulse amplitude, and the integrated concentration of GH were all lower than in 14 age- and sex-matched (10 pubertal and 4 prepubertal) control subjects. GH response to provocative stimuli was normal in the euthyroid patients. This pattern of response corresponds with the definition of neurosecretory dysfunction of GH secretion. It is concluded that the growth retardation of patients with thalassemia major is partly due to neurosecretory dysfunction of GH secretion.     

Effect of booster blood transfusions on oxygen utilization in infants with bronchopulmonary dysplasia

To assess the impact of booster transfusions on oxygen utilization in infants with bronchopulmonary dysplasia, we noninvasively measured oxygen consumption (VO2) and the variables of systemic oxygen transport (SOT) before and 24 hours after transfusion therapy in 10 oxygen-dependent infants with bronchopulmonary dysplasia. The infants had been born with a mean gestational age of 27.6 weeks and a mean birth weight of 0.88 kg. Study weight averaged 1.24 +/- 0.35 kg, and study age averaged 5.5 +/- 2.4 weeks. Requirements for fractional concentration of inspired oxygen averaged 0.41 +/- 0.15 to maintain an oxygen saturation of 0.93 +/- 0.02. The VO2 was measured by means of a commercially available analyzer through a flow-through circuit and pump connected to a hood or in line with the ventilator. Cardiac output was calculated by means of pulsed Doppler ultrasonography. Oxygen saturation was measured by means of transcutaneous pulse oximetry. The coefficient of oxygen utilization was calculated as VO2/SOT. Transfusion consisted of packed erythrocytes (10 ml/kg). Oxygen utilization fell in all subjects after transfusion (p less than 0.01), but it fell more substantially in subjects with higher coefficients of oxygen utilization (r = -0.80, p less than 0.01), suggesting a physiologic benefit in selected patients, particularly those with higher levels of oxygen utilization. There was also a significant increase in overall systemic oxygen transport (p less than 0.01) and decrease in VO2 (p less than 0.02). Hemoglobin levels alone did not correlate with overall systemic oxygen transport, VO2, or level of oxygen use before transfusion, and thus did not predict which subjects would have a physiologic benefit from transfusion as reflected by falls in oxygen utilization.     

Thalassemia major may decrease the frequency of febrile convulsions in children

Aim: We aimed to determine the relative frequency of febrile convulsion in children with major thalassemia to theorize that higher serum iron levels could reduce the incidence of febrile convulsion. Background: Febrile convulsion is the most common type of seizure in childhood that its causes are not fully understood. However, some risk factors have been cited such as the serum iron level. Materials and methods: Three hundred and fifty-nine children aged more than 5 years with major thalassemia who were receiving blood were enrolled as the case group. The control group consisted of 357 children without thalassemia aged 4–7 years (151 boys, 206 girls) who were referred to healthcare centers for routine health monitoring. Included data were the history of febrile convulsion, age of onset and type and the frequency of convulsions. Results: Children in control group significantly experienced more febrile convulsions than thalassemic children [4/359 (1.1%) in the thalassemic children and 14/357 (3.9%) in the control group had experienced febrile convulsions (P = 0.017)]. Conclusion: The frequency of febrile convulsion in children with major thalassemia is less than that of normal children. Children with thalassemia major may have higher serum levels of iron and such high serum iron levels might have a protective role in the children who have a vulnerability for febrile convulsions.     

Effect of high doses of human recombinant erythropoietin on the need for blood transfusions in preterm infants.

To determine whether prophylactic treatment with recombinant human erythropoietin (rHuEPO) and iron would reduce the need for blood transfusions, we randomly assigned 22 premature infants with gestational ages less than or equal to 32 weeks and birth weights less than or equal to 1.75 kg to receive rHuEPO, 400 IU/kg three times a week, plus iron, 20 mg/wk intravenously, from the second day of life (11 infants), or no rHuEPO and no iron (11 infants). The two groups had similar birth weights and clinical variables. The treated infants required fewer blood transfusions (0.8 +/- 1.5 vs 3.1 +/- 2.1; p = 0.01) and less volume of packed erythrocytes (14.2 +/- 25.9 vs 48.4 +/- 34.0 ml/kg; p = 0.02). The amounts of blood sampled were not different (19.5 +/- 21.1 vs 27.8 +/- 19.1 ml/kg; p = 0.35). Reticulocyte and hematocrit values were higher in the treated group (4.46% +/- 0.8% vs 1.49% +/- 1.1% (p = 0.0001) and 48.1% +/- 7.3% vs 43.8% +/- 4.7% (p = 0.004), respectively). No side effects of either rHuEPO or intravenously administered iron were noted. These data indicate that rHuEPO, in combination with iron supplementation, is effective in reducing the need for blood transfusions in the premature infant. More information is needed on dosage, timing, and iron and vitamin supplementation.     

Hepatic and Cardiac Iron-load in Children on Long-term Chelation with Deferiprone for Thalassemia Major

Objective

To evaluate the efficacy of prolonged deferiprone monotherapy in patients with β-thalassemia major.

Methods

This cross-sectional study included 40 patients (age range 9 to 38 years) with thalassemia major receiving deferiprone for ≥5 years. Serum ferritin, and myocardial iron concentration (MIC) and liver iron concentration (LIC) assessed by T2*MRI were recorded.

Results

The patients were receiving deferiprone for a mean (SD) duration of 12.1 (4.7) years. The median (IQR) dose of deferiprone was 85 (74.3, 95) mg/kg/day. The MIC was normal or had a mild, moderate or severe elevation in 29 (72.5%), 3 (7.5%), 3 (7.5%), and 5 (12.5%) patients. The LIC was normal or had a mild, moderate or severe elevation in 2 (5%), 4 (10%), 11 (27.5%) and 23 (57.5%) patients.

Conclusions

The majority of patients receiving deferiprone had a moderate/severe hepatic but normal cardiac iron load. Prolonged deferiprone monotherapy was suboptimal for hepatic iron load in the majority.

     

Effect of donor-specific transfusions on renal transplantation in children

Most family members who are evaluated as kidney donors for children have high reactivity in a mixed lymphocyte culture test and are thus excluded from donation. Fifty children, most of whom had highly reactive mixed lymphocyte cultures with their donors, were challenged with three blood transfusions from their donors before transplantation and were tested for the development of lymphocytotoxic antibodies. Ten children (20%) became sensitized and had a positive T-cell or B-cell crossmatch. Sensitization occurred less frequently in children treated with azathioprine during donor-specific transfusions (11%) than in those not treated (26%), but the difference was not significant. Thirty-seven children received renal transplants from their blood donors after the donor-specific transfusions. There were no deaths, and only two patients had kidney failure. Actuarial kidney survival was 93% after 6 years. The use of donor-specific transfusion has increased the number of related-donor transplants performed and the results have been highly successful.     

Assessment of Cardiac Parameters in Evaluation of Cardiac Functions in Patients with Thalassemia Major

The aim of the study was to evaluate cardiac function and early cardiac dysfunction of patients followed as thalassemia major. In this study, the authors compared 100 patients, diagnosed as thalassemia major with mean age 11.84 ± 4.35, with 60 healthy control subjects at the same age between 2008 and 2011. Early diagnosis of iron overload that may occur after repeated transfusions is important in this patient group. To detect early iron accumulation, the authors compared ferritin with the echo findings, the 24-hour Holter, and cardiac magnetic resonance imaging (MRI) T2* values in the patients of same age and sex, treated with chelators, without heart failure, nonsplenectomized, and do not differ in the presence of hepatitis C. Ferritin levels, left ventricular systolic functions (ejection fraction [EF], shortening fraction [SF]), left ventricular measurements, left ventricular diastolic functions, T2* image on cardiac magnetic resonance, heart rate variables in 24 hours, and Holter rhythm were evaluated to show the early failure of cardiac functions. In this study the authors confirmed that iron-related cardiac toxicity damages electrical activity earlier than myocardial contractility. Left ventricular diastolic diameter (LVDd), left ventricular mass (LVM), and LV systolic diameter (LVDs) levels were significantly higher in the patient group with ectopia. Patients with ectopia are the ones in whom LVM and LVDd are increased. In thalassemia major patients with ectopia, LF/HF ratio was markedly increased, QTc dispersion was clearly found higher in patients with ectopia rather than nonectopic patients. The standard deviation all normal RR interval series (SDNN) was found clearly lower in thalassemia major group with ectopia than control group because it is assumed that increase in cardiac sympathetic neuronal activity is related to exposure to chronic diastolic and systolic failure.