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Abstract Purpose This study aimed to evaluate the knowledge, attitude, and practice toward iron chelating agents (ICAs) in Iranian thalassemia major patients. Methods A total of 101 patients with thalassemia major were involved in this cross-sectional survey. A deep medication review was done, and participants’ knowledge, attitude, and practice were evaluated by a validated instrument based on a 20-scoring system. Results Statistical analyses showed 52 patients (51.5%) had a poor knowledge level (scores 15). Seventy-seven (76.2%) patients have positive beliefs regarding the dependence of their current health status on taking iron chelators, and 63 (62.4%) believed that they would become very ill without taking medication. The results also showed that the mean practice score in patients who received deferoxamine was 5.81 ± 3.50; in the patients who received deferiprone and those who received deferasirox, the mean scores were 7.36 ± 5.15 and 14.94 ± 4.14. Also, the knowledge and practice level had a direct linear correlation based on the regression analyses (P

Background: Screening tests on blood bags is important step for blood safety. In Iran, screening for HCV started from 1996. We decided to determine the new cases of hepatitis C in our thalassemic patients, after screening of blood bags was initiated and trace backing from recipients to find their donors. Materials and Methods: The study was done on patients with complete files for HCVAb test results. Only cases that had a positive HCVAb result following a negative result were considered as new cases. For trace backing, we recorded the blood transfusions′ date and the blood bags′ number from last negative test results (HCVAb) to the first positive test result. These data were sent to the transfusion center. The suspected donors were contacted and asked to be tested again in the transfusion center. Results: A total of 395 patients were studied; 229 (58%) males and 166 (42%) females. Mean age was 27.5 years. We had 109 HCV (27.5%) positive cases of whom 21 were infected after 1996. We traced the last five cases contaminated during 2003 and 2004. These five patients had 13, 10, 13, 12, and 6 donors, respectively (totally 54 donors were found). We proved the healthy state in 68.5% (37 of 54) of our donors population. Of them, 81% were repeated donors and 17 of 54 donors (31.5%) could not be traced (because of change in addresses). We did not have any HCV new cases after 2004. Conclusion: We could not prove HCV transmission from donors as the source of infection. Although parenteral transmission is always on top of the list in HCV infection, the possibility of hospital and/or nursing personnel transmission and/or patient-to-patient transmission such as use of common instruments like subcutaneous Desferal® infusion pumps; which the patients used for iron chelation therapy, should also be kept in mind.

Abstract Next-generation sequencing (NGS) has been proven to be one of the most powerful diagnostic tools for rare Mendelian disorders. Several studies on the clinical application of NGS in unselected cohorts of Middle Eastern patients have reported a high diagnostic yield of up to 48%, correlated with a high level of consanguinity in these populations. We evaluated the diagnostic utility of NGS-based testing across different clinical indications in 1436 patients from Iran, representing the first study of its kind in this highly consanguineous population. A total of 1075 exome sequencing and 361 targeted gene panel sequencing were performed over 8 years at a single clinical genetics laboratory, with the majority of cases tested as proband-only (91.6%). The overall diagnostic rate was 46.7%, ranging from 24% in patients with an abnormality of prenatal development to over 67% in patients with an abnormality of the skin. We identified 660 pathogenic or likely pathogenic variants, including 241 novel variants, associated with over 342 known genetic conditions. The highly consanguineous nature of this cohort led to the diagnosis of autosomal recessive disorders in the majority of patients (79.1%) and allowed us to determine the shared carrier status of couples for suspected recessive phenotypes in their deceased child(ren) when direct testing was not possible. We also highlight the observations of recessive inheritance of genes previously associated only with dominant disorders and provide an expanded genotype–phenotype spectrum for multiple less-characterized genes. We present the largest mutational spectrum of known Mendelian disease, including possible founder variants, throughout the Iranian population, which can serve as a unique resource for clinical genomic studies locally and beyond.

Introduction: Multi-organ iron load is prevalent crucial side effect in thalassemic patients due to repeated transfusions, and high intestinal iron absorption. MRI T2* has demonstrated its potency as a non-invasive technique for the imaging of hemosiderosis in thalassemia. We aim to investigate the iron load of adrenal glands and kidneys using MRI T2* in adult thalassemia patients and evaluate the serum ferritin correlation of with kidneys, heart, liver, and adrenal glands’ iron load.Methods: Thirty-five thalassemia major (TM) and thalassemia intermediate (TI) patients (age range 18-50 years) from Zafar thalassemia Clinic, were recruited in this survey from September 2019 to October 2020. Magnetic Resonance Imaging (MRI) was used to map iron overload in several organs’ regions of interest (ROIs) using fast-gradient-echo multi echo T2*sequences protocol. T-test and chi-square analysis were done.Results: Nine (25.7%) patients had left Kidney T2* less than 36ms which could indicate abnormal renal iron load while this was 8 (22.9%) for the right kidney. In the left and right adrenal glands, these numbers were 31 (88.6%) and 29 (82.9%), respectively, below the normal threshold.Conclusion: Adrenal gland and renal iron overloads were detected in MRI images of thalassemic patients. Correlation for serum ferritin levels and kidney and adrenal glands T2* was found weakly negative. Non-invasive monitoring of the internal organs’ hemosiderosis using MRI T2* was found to be beneficial for iron-chelating optimization and preventing irreversible tissue damage.

Introduction: Thalassemia consists of a variety of genetic hemoglobinopathies. Thalassemia-major causes anemia in early age. Those suffering from thalassemia need frequent life-long blood transfusions to survive, resulting in iron overload in the body and many health problems. Much improvement has occurred in predicting the course of Thalassemia major thanks to iron chelation therapy. Edible iron chelating agents are the standard of the chelating process. Deferasirox is a newly developed orally active iron chelating tablet which is used on a daily basis. Th present case study investigated severe dermatopathological reactions to the Iranian made product of Deferasirox.Case presentation: We present a case of adverse drug reactions in a thalassemic patient who was started on Deferasirox orally after receiving Deferoxamine injections for several years with no serious reactions. The patient experiences generalized maculopapular, deep red- blue partially purpuric itchy skin rashes throughout her body. The histopathological biopsy found superficial perivascular or dermatitis with low-grade vasculopathy, few eosinophils, and mild psoriasis form-supraglotticlichenoid epidermal reactions associated with Drug Reaction diagnosis.Conclusion: With regard to inherent features, caution must be applied to start the original Deferasirox for the patients who will undergo the oral chelation process with a smooth increase in the daily dosage for a few weeks in order to create improved tolerance.

Abstract Background and Aims One of the most common hemoglobinopathies globally related to blood transfusion and iron overload in the body is thalassemia syndrome. Increasing ferritin levels can cause severe damage to the patient's body organs. This study aims to evaluate the complications of iron overload on vital body organs in patients with transfusion‐dependent beta‐thalassemia. Methods This descriptive cross‐sectional study was performed in Iran University of Medical Sciences Hospitals on patients with a beta‐thalassemia major with frequent blood transfusions. To evaluate the effect of iron overload on vital body organs, hematologic and blood analysis, echocardiography with measurement of pulmonary artery pressure (PAP) and ejection fraction (EF) tests, bone densitometry, and audiometric tests were performed for all patients. Results Of the 1010 patients participating in this study, 497 (49%) were males, 513 were (51%) females aged 5–74 years, and the majority of participants (85%) were over 20 years old. This study demonstrated that increasing ferritin levels had no notable correlation with sex, cholesterol, low‐density lipoprotein, parathyroid hormone, T4, and aspartate aminotransferase. However, elevating ferritin levels had significant correlations with increasing triglyceride, phosphorus, thyroid stimulating hormone, alkaline phosphatase, alanine transaminase, and PAP levels, age, hearing disorders, splenectomy, osteoporosis, and decreasing high‐density lipoprotein, body mass index, calcium, and EF levels. Conclusion Improvement in beta‐thalassemia patients' survival and quality of life can be due to multidisciplinary care in a comprehensive unit through regular follow‐up and early complication detection.

Background: Thalassemia is a congenital disease and Iran is as one of the countries in the thalassemia belt. It has a huge burden in Iranian national health budget. The aim of this study was to develop a questionnaire to assess the knowledge and practice of thalassemia patients toward their medications. Methods: This is a methodological research, which was done from April 2020 to November 2021 in Tehran, Iran, to develop a valid and reliable instrument for measuring major thalassemia patients’ knowledge and practice regarding their medications, a questionnaire based on three iron chelating medications (deferoxamine, deferiprone, and deferasirox) developed. This process done by holding several expert panel meetings. This questionnaire was consisting of some aspects such as: administration, self-monitoring, miss dose, common interactions, and adverse events. Content validity index (CVI) and internal consistency and reliability were calculated. Results: The CVI was as 0.76 for deferoxamine, 0.80 deferiprone and 0.88 for deferasirox questionnaire. Further analysis for internal consistency demonstrated satisfactory results with Cronbach’s alpha coefficients ranging from 0.743 to 0.781. Results showed Thalassemia Medication Questionnaire (TMQ) demonstrated acceptable validity and reliability for application. Conclusion: It was concluded that TMQ could be a useful instrument to measure knowledge and practice about iron chelation therapy. The reason is the diverse range of questions and the simplicity, validity, reliability, and the practicability.

Objective: We evaluated the accuracy of two-dimensional speckle-tracking echocardiography (2DSTE) and 3DSTE to identify early cardiac dysfunction in comparison with cardiac T2* magnetic resonance imaging (MRI) in patients with blood transfusion-dependent β-Thalassemia. Methods: A total of 48 consecutive patients (36 males) successfully underwent 2DSTE, 3DSTE, and MRI on the same day. We calculated left ventricular segmental global longitudinal strain (GLS) (%) and segmental global circumferential strain (GCS) (%) from strain curves. Cardiovascular MRI was performed with the relevant protocols to measure the T2*. Results: In this study, we found that the GLS and GCS derived from 3DSTE correlated with cardiac T2* (r = −0.50, r = −0.49, respectively), whereas no correlation was detected between 2DSTE parameters and cardiac T2*. We calculated the area under the receiver operating characteristic area under the curve to determine the capability of 3DSTE parameters including GLS (

Abstract Background β Thalassemia is one of the most common groups of hereditary haemoglobinopathies. Affected people with thalassemia major are dependent on regular blood transfusion which on the long term leads to iron overload. Hepcidin is a peptide hormone and an important regulator of iron homeostasis, especially in thalassemia. Expression of this hormone is influenced by polymorphisms within the hepcidin gene, HAMP. Several studies emphasized the role of single nucleotide polymorphisms (SNPs) located in the promoter region of the gene. This study aimed to analyze the association between three SNPs in promoter of HAMP, c.-582A > G, c.-443C > T, and c.-153C > T, with iron overload in β-thalassemia major patients. Methods A total of 102 samples from β thalassemia major patients were collected. Genomic DNA was extracted and segments of DNA encompassing rs10421768 and rs142126068 were sequenced. Statistical analysis was performed by SPSS Statistics 23 using independent t test and Fisher’s exact test. Results A total of 102 adult β-thalassemia major patients were genotyped for three SNPs in the promoter region of HAMP gene by PCR and direct sequencing. Most of the patients (71.3%) were iron overloaded (based on plasma ferritin > 1000 ng/ml) in spite of receiving regular iron-chelating therapy. Our analysis revealed a statistically significant difference between the level of cardiac iron accumulation and c.-582A > G variant (p = 0.02). For c.-443C > T statistical analysis was on the edge of the significant relationship between the minor allele and serum ferritin (p = 0.058). All samples were homozygous for allele C of c.-153C > T. Conclusions Despite chelating therapy, iron overload is still one of the main complications of thalassemia. Our findings and others emphasize the role of hepcidin -582A > G polymorphism as a key component of iron homeostasis in these patients.

Abstract Objectives Serological methods may not be reliable for RBC antigen typing, especially in multi‐transfused patients. The blood group systems provoking the most severe transfusion reactions are mainly Rh, Kell, Kidd, and Duffy. We intended to determine the genotype of these blood group system antigens among Iranian alloimmunized thalassemia patients using molecular methods and compare the results with serological phenotyping. Methods Two hundred patients participated in this study. Blood group phenotype and genotype were determined using the serological method and PCR‐SSP, respectively. The genotypes of patients with incompatibility between phenotype and genotype were re‐evaluated by RFLP‐PCR and confirmed by DNA sequencing. Results Discrepancies between phenotype and genotype results were found in 132 alleles and 83 (41.5%) patients; however, there was complete accordance between the three genotyping methods. Most discrepancies were detected in Rh and Duffy systems with 47 and 45 cases, respectively, and the main discrepancy was in the FY*B/FY*B allele when serologically showed Fy(a+b+). All 39 undetermined phenotypes, due to mixed‐field reactions, were resolved by molecular genotyping. Conclusion Molecular genotyping is more reliable compared with the serological method, especially in multi‐transfused patients. Therefore, the addition of blood group genotyping to serological assays can lead to an antigen‐matched transfusion in these patients.

Introduction: Multi-organ iron load is prevalent crucial side effect in thalassemic patients due to repeated transfusions, and high intestinal iron absorption. MRI T2* has demonstrated its potency as a non-invasive technique for the imaging of hemosiderosis in thalassemia. We aim to investigate the iron load of adrenal glands and kidneys using MRI T2* in adult thalassemia patients and evaluate the serum ferritin correlation of with kidneys, heart, liver, and adrenal glands' iron load. Methods: Thirty-five thalassemia major (TM) and thalassemia intermediate (TI) patients (age range 18-50 years) from Zafar thalassemia Clinic, were recruited in this survey from September 2019 to October 2020. Magnetic Resonance Imaging (MRI) was used to map iron overload in several organs' regions of interest (ROIs) using fast-gradient-echo multi-echo T2*sequences protocol. T-test and chi-square analysis were done. Results: Nine (25.7%) patients had left Kidney T2* less than 36ms which could indicate abnormal renal iron load while this was 8 (22.9%) for the right kidney. In the left and right adrenal glands, these numbers were 31 (88.6%) and 29 (82.9%), respectively, below the normal threshold. Conclusion: Adrenal gland and renal iron overloads were detected in MRI images of thalassemic patients. Correlation for serum ferritin levels and kidney and adrenal glands T2* was found weakly negative. Non-invasive monitoring of the internal organs' hemosiderosis using MRI T2* was found to be beneficial for iron-chelating optimization and preventing irreversible tissue damage. [ABSTRACT FROM AUTHOR]

Introduction: Thalassemia consists of a variety of genetic hemoglobinopathies. Thalassemia-major causes anemia in early age. Those suffering from thalassemia need frequent life-long blood transfusions to survive, resulting in iron overload in the body and many health problems. Much improvement has occurred in predicting the course of Thalassemia major thanks to iron chelation therapy. Edible iron chelating agents are the standard of the chelating process. Deferasirox is a newly developed orally active iron chelating tablet which is used on a daily basis. Th present case study investigated severe dermatopathological reactions to the Iranian made product of Deferasirox. Case presentation: We present a case of adverse drug reactions in a thalassemic patient who was started on Deferasirox orally after receiving Deferoxamine injections for several years with no serious reactions. The patient experiences generalized maculopapular, deep red-blue partially purpuric itchy skin rashes throughout her body. The histopathological biopsy found superficial perivascular or dermatitis with low-grade vasculopathy, few eosinophils, and mild psoriasis form-supraglotticlichenoid epidermal reactions associated with Drug Reaction diagnosis. Conclusion: With regard to inherent features, caution must be applied to start the Deferasirox for the patients who will undergo the oral chelation process with a smooth increase in the daily dosage for a few weeks in order to create improved tolerance. [ABSTRACT FROM AUTHOR]

Background and Objectives: A small sample size can influence the results of statistical analysis. A reduction in the sample size may happen due to different reasons, such as loss of information, i.e. existing missing value in some variables. This study aimed to apply bootstrap and jackknife resampling methods in survival analysis of thalassemia major patients. Methods: In this historical cohort study, the data of 296 patients with thalassemia major who were visited at Zafar Clinic, Tehran, from 1994 to 2013 were used. Parametric survival models were used to analyze the data. The log – normal survival model was selected as the best model and then the bootstrap and jackknife resampling algorithms were used for this model. Data analysis was carried out with the STATA 12.0 software. Results: The results of the resampling methods showed that standard errors decreased and confidence intervals were shortened. In addition, the result of the bootstrap and jackknife resampling methods showed that age group and the relationship of the parents (P0.900). Conclusion: Comparison of the confidence intervals suggests that the jackknife resampling method can be used when the sample size is small.

Background: Human leukocyte antigen E is a member of non-classical HLA class I. Interaction between HLA-E molecule on the target cells and inhibitory CD94/NKG2A receptor on the cell surface of natural killer (NK) cells has an important role in the regulation of immune system against pathogens; therefore different cell surface expression of HLA-E molecule plays an important role in host resistance against viral infections as well as host response to treatment. Considering this fact, we analyzed the frequency of different HLA-E genotypes (HLA-E*01010101, HLA-E*01030103, HLA-E*01010103) in major thalassemic patients who underwent frequent transfusion therapy and are thus more susceptible to infectious diseases. Methods: This study was a cross-sectional study of 104 major thalassemic patients who referred to Tehran Thalassemia Clinic between the years 2015 to 2016. Blood DNA was extracted and proliferated by sequence-specific primer polymerase chain reaction (SSP PCR). The PCR product was subjected to electrophoresis on 1.5 percent agarose gel then DNA fragment bands on the gel were detected by exposing to UV light. Furthermore, PCR products were also subjected to sequencing analysis for further confirmation. Results: From 104 patients in this study, 49 (47.1%) were man and 55 (52.9%) were women. These patients were in the age range of 16 to 43 years (mean+SD; 31.03±4.7 year). The frequency of HLA-E*01010103 genotype (64.4 percent) was significantly (P= 0.001) higher than the genotypes of HLA-E*01010101 (15.4%) and HLA-E*01030103 (20.2%) whereas there was no difference between the frequency of HLA-E*0103 allele (52.4%) and HLA-E*0101 (47.6%). Conclusion: This is the first study that examined the HLA-E polymorphisms in Iranian thalassemic patients referred to Tehran Thalassemia Clinic. This study has shown that the frequency of HLA-E*01010103 genotype was significantly higher than other genotypes of HLA-E whereas there was no difference between the frequency of HLA-E*0103 allele and HLA-E*0101 allele. Whether different frequencies of HLA-E genotype may affect thalassemic patients’ susceptibility to blood-borne infections will be of interest for future studies.

Objectives: Many Iranian studies have reported the high prevalence of osteoporosis and low bone mass in patients with thalassemia. Considering the importance of prevention in lowering the risk of osteoporosis and its complications in patients with thalassemia major (TM), the present study was conducted to assess the knowledge, attitude and preventive practice (KAP) of a group of TM patients regarding the importance of calcium and Vitamin D supplementation and its role in preventing osteoporosis. Materials and Methods: The cross-sectional study was conducted on all adult beta-TM patients (200) who visited the Specific Disease Center, in the Iranian Capital, Tehran. A four-section questionnaire on demographic, lifestyle, and socioeconomic information as well as their KAP about the importance of calcium and Vitamin D in preventing osteoporosis in TM patients was filled out for each patient. Results: About 63%, 62%, and 33% of those with poor knowledge, attitude and practice towards the importance of calcium and Vitamin D were not physically active, correspondingly. There was no association between age and gender and knowledge or attitude score. Conclusion: While a large number of the studied population consumed Ca and Vitamin D supplementation, their poor knowledge about the importance of these supplements points out the need for educating TM patients and their families about the importance of calcium and Vitamin D supplementation in preventing osteoporosis.