Optical coherence tomography findings in patients with transfusion-dependent ß-thalassemia.

BACKGROUND: Structural ophthalmologic findings have been reported in patients with ß-thalassemia due to chronic anemia, iron overload, and iron chelation therapy toxicity in few previous studies. We aimed to investigate structural ocular findings and their relationship with hematological parameters in patients with transfusion-dependent ß-thalassemia (TDT). METHODS: In this cross-sectional study, from January 2018 to January 2019, 39 patients with TDT over the age of 18 participated. Multicolor fundus imaging, optical coherence tomography (OCT), and blue light fundus autofluorescence imaging were performed for all patients and 27 age- and sex-matched controls. RESULTS: The mean age of patients was 28.6 ± 6.2 years. The central macular thickness and macular thicknesses in all quadrants were significantly thinner in patients than controls (P<0.05). None of the retinal nerve fiber layer (RNFL) measurements were significantly different between TDT patients and controls. There was a significantly negative correlation between hemoglobin with central macula thickness (r=-0.439, P=0.005). All measurements of macular subfield thickness were insignificantly thinner in patients with diabetes mellitus (DM) compared to the non-DM subgroup. CONCLUSIONS: Macular thickness was significantly thinner in central macula and entire quadrants in TDT patients compared to healthy individuals; however, all RNFL measurement thicknesses were comparable between the two groups. Close monitoring of TDT patients by periodic ophthalmologic examinations with more focus on diabetic patients, patients with severe anemia and iron overload should be warranted.

Bayesian spatial modeling of transfusion-dependent ß-thalassemia incidence rate in Fars Province, Southern Iran.

BACKGROUND: Using maps and spatial analysis are technologies to evaluate the magnitude and spatial distribution of disease in epidemiology investigations. We aimed to conduct a Bayesian spatial analysis on epidemiologic data of transfusion-dependent ß-thalassemia (TDT) patients. METHODS: In this cross-sectional study, data of all TDT patients diagnosed during 1955-2018 in all counties of Fars Province were obtained from data registry of the Organization of Special Diseases of Shiraz University of Medical Sciences in Shiraz, Fars Province, Iran. Besag, York, and Mollie's (BYM) model was used for mapping. RESULTS: The estimated relative risk ranged from 0.23 to 1.66 for TDT patients. The highest and lowest relative risks of TDT were observed in Larestan located in Southern and Abadeh in Northern Fars Province respectively. CONCLUSIONS: Determining the accurate geographical distribution of a chronic disease such as ß-thalassemia can be an essential prerequisite in allocation of regional health system resources.

Effects of three months of treatment with vitamin E and N-acetyl cysteine on the oxidative balance in patients with transfusion-dependent ß-thalassemia.

Oxidative stress is a major mechanism contributing to the progression of ß-thalassemia. To assess the effect of vitamin E and N-acetyl cysteine (NAC) as antioxidant agents on total oxidative stress (TOS) status and total antioxidant capacity (TAC) in patients with transfusion-dependent ß-thalassemia (TDT). In this open-label randomized controlled trial, from May to August 2019, 78 eligible patients with TDT over the age of 18 were enrolled. All patients were registered at the Thalassemia Clinic of Shiraz University of Medical Sciences in Southern Iran. Patients were randomly allocated to the NAC group (10 mg/kg/day, orally), vitamin E group (10 U/kg/day, orally), and control group. The duration of the study was 3 months. The mean age of the participants was 28.5 ± 5.1 (range: 18-41) years. At the end of the study, TOS significantly decreased only in the vitamin E group (mean difference (MD), 95% confidence interval (CI): 0.27 (0.03-0.50), P = 0.026). TAC significantly decreased in both supplemented groups at the 3rd month of treatment (NAC group: MD (95% CI): 0.11 (0.04-0.18), P = 0.002 and vitamin E group: 0.09 (0.01-0.16), P = 0.022 respectively). Hemoglobin did not significantly change at the end of the study in each group (P > 0.05). Mild transient adverse events occurred in 4 patients of the NAC group and 5 patients of the vitamin E group with no need to discontinue the treatment. Vitamin E can be a safe and effective supplement in improving oxidative stress in patients with TDT. Moreover, it seems that a longer duration of using antioxidant supplements needs to make clinical hematologic improvement in TDT patients.

Ocular findings in patients with transfusion-dependent ß-thalassemia in southern Iran.

BACKGROUND: Ocular involvement may occur via several mechanisms in patients with transfusion-dependent ß-thalassemia (TDT) mainly chronic anemia, iron overload and iron chelator toxicity. We aimed to evaluate the frequency of abnormal ocular findings and their relationship with hematologic parameters in TDT patients. METHODS: In this cross-sectional study from January 2018 to January 2019, a total of 79 patients with TDT over the age of 18 who were on iron-chelation therapy (ICT) were consecutively investigated. All patients were registered at the Thalassemia Comprehensive Center affiliated with Shiraz University of Medical Sciences, Shiraz, Southern Iran. Complete ophthalmic examination was performed by an expert ophthalmologist. Clinical and hematologic parameters were collected from the patients´ medical records. RESULTS: The mean age ± standard deviation (SD) of the patients was 28.4 ± 5.6 years (range: 18-43). Twenty-four patients (30.4%) were male and 29 (36.7%) were splenectomized. The mean ± SD of the best-corrected visual acuity (VA) was 0.960 ± 0.086 decimal, (range: 0.6-1), 0.016 ± 0.046 logMar, (range: 0-0.2). The frequency of patients with VA > 0.1 logMar was 3 (3.8%). The mean intraocular pressure (IOP) was 14.88 ± 3.34 (6-25) mmHg. Fundus abnormalities were observed in 8 patients (10.1%), consisting of increased cup-disk ratio (3.8%), vessel tortuosity (2.5%), retinal pigment epithelium degeneration (2.5%), myelinated nerve fiber layer (1.3%), and internal limiting membrane wrinkling (1.3%). No significant association was observed between fundus abnormalities, VA, or IOP with hematologic parameters (P > 0.05). TDT patients with diabetes mellitus had significantly higher IOP (P = 0.010) but similar frequency of fundus abnormalities with non-diabetic patients (P > 0.05). CONCLUSIONS: The frequency of ocular abnormalities in our patients was lower than the previous reports. The frequency of fundus abnormalities were similar in diabetic and non-diabetic thalassemia patients indicating close monitoring and proper management of the disease and comorbidities in these patients.

Frequency of silent brain lesions and aspirin protection evaluation over 3 years follow-up in beta thalassemia patients.

Silent brain lesions might be associated with overt cerebrovascular accident over time in beta thalassemia major (BTM) and intermediate (BTI). Aspirin may be protective in these patients. We evaluated brain magnetic resonance imaging (MRI) in thalassemia patients to see whether aspirin is protective or not. A historical cohort study was conducted on 35 thalassemia patients, 22 BTI, and 13 BTM patients at Shiraz Hematology Research Center in 2018. Median age of the patients was 32 years and ranged from 8 to 42 years. Twenty-four patients (68.6%) were females. Overall frequency of white matter lesions (WMLs) in the first MRI was 10 patients (28.6%). After 3 years, 3 patients developed new lesions and the frequency of WMLs was 13 patients (37.1%) in the second MRI. Moreover, in 3 patients, number of WMLs increased. Patients with new lesions or more lesions compared to the baseline were significantly older than the other group (median age 36.5 years vs. 31 years, P = 0.046). Regarding aspirin consumption, only 1 patient (16.7%) of patients with new lesions was using aspirin compared to 10 (34.5%) of the other group (P = 0.640). The high-risk patients with thrombocytosis, splenectomy, severe iron overload, and older age (> 30 years) should be under close follow-up and evaluated on a regular periodic basis as well as brain MRI at least once every 3 years. Aspirin could be protective against new or progressive brain lesions so that low-dose aspirin is recommended in high-risk thalassemia patients.

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

ß-Thalassemia (ß-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 ß-thal major (ß-TM) patients. In this semi-experimental study, 112 ß-TM were randomly selected and assigned to the study and control groups. Seven ß-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 ß-TM patients in the study group compared to the control group, which may be used as a frontline educational model in these patients.

Complementary and alternative medicine use in thalassemia patients in Shiraz, southern Iran: A cross-sectional study.

This study aimed to determine the frequency and pattern of complementary and alternative medicine (CAM) use in thalassemia patients in south of Iran. The survey was done using a validated questionnaire which was distributed among 122 thalassemia patients. Only 108 questionnaires were completed and turned back (response rate 88.5%). Patients referred to an outpatient thalassemia clinic in Shiraz, southern Iran for blood transfusion. The mean age of the patients was 22.9 ± 7.9 years (range 4-45 years) with female/male ratio 1.84. Seventy four (68.5%) of the responders used CAM at least once during their life, and about half of them used it concurrently with their conventional treatments. The most reported CAM product was mint juice (50%). The most common reason of CAM use was increased general health. The most common information source about CAM was physicians who were the most trusted source as well. CAM is frequently being used in thalassemia patients to ensure their sense of well-being and help them overcome the complications of their illnesses.

Health-Related Quality of Life and Health Utility Values in Beta Thalassemia Major Patients Receiving Different Types of Iron Chelators in Iran.

Background: Thalassemia is a chronic, inherited blood disorder, which in its most severe form, causes life-threatening anemia. Thalassemia patients not only engage with difficulties of blood transfusion and iron chelating therapy but also have some social challenges and health threatening factors. There are some reports on quality of life in thalassemia patients around the world from southeast of Asia to Italy in Europe and United States. In this study, we tried to evaluate and compare Health Related Quality of life (HRQoL) and the health utility in beta thalassemia major patients receiving different types of iron chelators and living in different socio-economical situations. Subjects and Methods: EQ-5D-3L accompanied by a Visual Analogue Scale (VAS) questionnaire was used. The respondents were patients with beta thalassemia major that were at least 12 years old selected from 3 provinces of Sistan-Blouchestan, Fars and Mazandaran. Comorbidities including heart complication, Diabetes Mellitus and Hepatitis and also types of iron chelators (oral, injection, combination of both) were also asked. Cross tab and ANOVA analysis conducted to evaluate each dimension score and health utility differences between provinces, iron chelation methods, comorbidities, age group and gender. Results: 528 patients answered the questionnaires. The health utility of patients that received oral iron chelator were 0.87 ± .01 for oral iron chelators versus 0.81 ± .01 for injection dosage form (p<0.05). Increase in age was accompanied by decrease in health utility. Females faced more usual activity problems, anxiety and depression. Heart problems were more prevalent in males. Conclusion: This study suggests that the quality of life of beta thalassemia major patients is dependent on type of iron chelation treatment which they received, the gender they have, the comorbidities they suffer and socio-economical situations they live in.

Relationship Between Serum Hepcidin and Ferritin Levels in Patients With Thalassemia Major and Intermedia in Southern Iran.

BACKGROUND: Hepcidin is a key regulator of iron absorption in humans. It is mainly affected by hypoxia and iron stores. OBJECTIVES: The current study aimed to determine the correlation between serum hepcidin and ferritin levels in patients with Thalassemia Major (TM) and Thalassemia Intermedia (TI). PATIENTS AND METHODS: The current cross-sectional study investigated 88 randomly selected patients with Thalassemia, 48 TM and 40 TI, registered at the Thalassemia Clinic of Shiraz University of Medical Sciences, a referral center for Thalassemia in Southern Iran in 2013. All patients with TI were receiving Hydroxyurea (HU) 10 - 15 mg/kg/day for at least 10 years. The serum hepcidin, ferritin levels, hemoglobin (Hb) and nucleated Red Blood Cell (RBC) of the two groups were measured. RESULTS: No statistically significant correlation was observed between serum hepcidin and ferritin levels in any of the two groups of patients with TM (rs = 0.02, P = 0.892) or TI (rs = 0.055, P = 0.734). The median Interquartile Range (IQR) for serum hepcidin and ferritin levels were significantly higher in TM compared to TI group, (hepcidin: 87.6 (43.9) vs. 51.8 (23.4), P < 0.001; ferritin: 2208 (3761) vs. 465 (632), P < 0.001). CONCLUSIONS: There was insignificant correlation between serum hepcidin and ferritin levels in the two groups of patients with TM and TI. It seems that regulation of hepcidin in patients with Thalassemia is more affected by erythropoeitic activity than iron stores. Also, hepcidin levels were significantly higher in patients with TM than TI, possibly due to higher erythropoeitic activity in TI. In TI, it seems that low dose HU increases Hb levels and leads to transfusion-independence, but it is not high enough to suppress bone marrow activity and ineffective erythropoiesis. Consequently, serum hepcidin level decreases.

Analysis of survival data in thalassemia patients in Shiraz, Iran.

OBJECTIVES: The survival rate of thalassemia patients has not been conclusively established, and the factors associated with survival remain unclear. This study aimed to determine the survival rate of thalassemia among patients in southern Iran and to identify the factors associated with mortality from thalassemia. METHODS: This retrospective cohort study was conducted based on a retrospective review of the medical records of 911 beta-thalassemia patients in 2014. Data analysis was conducted using the Kaplan-Meier method and Cox regression analysis. RESULTS: Overall, 212 patients (23.3%) died, and 26.8% had thalassemia intermedia. The 20-year, 40-year, and 60-year survival rates were 85%, 63%, and 54%, respectively. Both crude and adjusted analyses found that education, marital status, ferritin levels, and comorbidities were related to mortality. CONCLUSIONS: Sociodemographic and hematological factors were found to be significantly associated with the survival rate of thalassemia. Addressing these factors may help healthcare providers and physicians to provide the best possible care and to improve the survival rate.

Efficacy of Deferasirox (Exjade®) in Modulation of Iron Overload in Patients with ß-Thalassemia Intermedia.

Because of insufficient erythropoiesis, peripheral hemolysis and increased gastrointestinal iron absorption, iron overload is still a matter of debate in ß-thalassemia intermedia (ß-TI) patients, which can be overcome using iron chelators. However, data on use of iron chelators in ß-TI patients is highly restricted. The aim of this study was to evaluate the efficacy of oral administration of deferasirox (Exjade(®) or DFX) by assessment of serum ferritin levels in ß-TI patients. In this quasi-experimental study, 50 ß-TI patients with serum ferritin levels >1000 ng/mL were selected and received oral DFX for 12 consecutive months. Iron overload was measured by checking serum ferritin levels every 2 months and the results were compared with the baseline level. The mean serum ferritin was decreased during 1 year of chelation therapy without any toxic effect. Although the difference between baseline ferritin and ferritin levels at the end of second month was not remarkable (p = 0.88), a significant reduction in serum ferritin was observed after 4 (p = 0.01), 6 (p = 0.001), 8 (p < 0.001), 10 (p < 0.001) and 12 months (p < 0.001) of chelation therapy compared to its baseline levels. There was no correlation between baseline ferritin levels and age (p = 0.574). In addition, no statistically significant difference was observed about change in serum ferritin levels after 6 and also 12 months of therapy between patients who had undergone splenectomy and those who did not (p = 0.796 and 0.859, respectively). Iron chelation therapy with DFX is safe and effective in reducing serum ferritin levels in ß-TI patients who suffer from side effects of iron overload.