Thalassemia Center Research Articles

Effect of deferasirox on renal function in thalassemic children

Abstract Background: Iron-chelating therapy causes improvement in the life expectancy of thalassemic patients. Deferasirox (DFX) is an oral iron chelator with an established dose-dependent efficacy, though alteration of renal function has been observed in many studies. In the present study, we evaluated the effect of treatment with DFX on renal function. Materials and Methods: This quasi-experimental study was done in the Thalassemia Center of Bangladesh Shishu Hospital and Institute from June 2019 to July 2021, where 50 thalassemia major and E-β thalassemia children aged 2–18 years old were included. Blood urea nitrogen (BUN), serum creatinine, spot urinary protein creatinine ratio, spot urinary calcium creatinine ratio, and estimated glomerular filtration rate (eGFR) were measured. If renal functions were normal, DFX was started at a dose of 25 mg/kg/day. After 6 months of DFX treatment, the abovementioned investigations were repeated and analysis was done. The study variables were analyzed by paired t-test. P value <0.05 was considered significant. Results: The mean age of the thalassemic children was 5.21 ± 1.72 years. Before treatment, mean serum creatinine was 39.78 ± 3.12 μmol/L, and after 6 months, serum creatinine was increased but not statistically significant. The mean value was 40.50 ± 3.39 μmol/L after 6 months (P value 0.071). There was no significant change of BUN. Initially, the mean BUN was 3.39 ± 0.76 mmol/L, and 6 months after treatment, it was 3.45 ± 0.70 mmol/L. Initially, the spot urinary protein creatinine ratio was 0.12 ± 0.04, and after 6 months, the mean value was 0.43 ± 0.24. it was significantly increased (P value <0.001). Initially, the spot urinary calcium creatinine ratio was 0.068 ± 0.043, and after treatment, it was significantly raised. The mean value was 0.191 ± 0.168 (P value <0.001). After 6 months of treatment with DFX, 35 patients developed mild proteinuria, and eight patients developed hypercalciuria. There was no significant change of eGFR before and after treatment. Conclusions: In this study, we got significant proteinuria and hypercalciuria but nonsignificant changes in serum creatinine, BUN, and eGFR.

Prevalence and Management of Transfusional Iron Overload in Syrian Beta Thalassemia Major Patients Pre and during the Syrian Conflict.

The primary aim of this study was to evaluate the prevalence of iron overload and the real-world clinical effectiveness of the iron chelation therapies (ICTs) in Syrian patients with transfusion-dependent beta thalassemia major (BTM) prior to and during the ongoing Syrian conflict. This single-center, two-stage observational study was conducted at Homs National Thalassemia Center (HNTC) prior to (2009) and during (2019) the armed conflict. The prevalence and the severity of iron overload, as well as the effectiveness of four iron chelation regimens, were assessed using serum ferritin (SF) concentrations as a means of monitoring in two cohorts of BTM patients receiving deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), or a combination of DFO and DFP therapy in both years. Statistical analyses encompassed one-way ANOVA, Kruskal-Wallis, Mann-Whitney U, and chi-square (χ2) tests for the comparisons of the variables and the frequencies between the two cohorts and subgroups. We included all eligible BTM patients at HNTC in 2009 (n = 205) and 2019 (n = 172). Only 84 patients from the 2009 cohort were accessible in 2019. Our findings revealed that 98% and 89% of the patients had iron overload (SF ≥ 1500 ng/mL) and comparable elevated median SF concentrations (3868 and 3757 ng/mL) in 2009 and 2019, respectively (P = 0.275). Furthermore, patients on DFO demonstrated the poorest control of iron overload and the highest SF concentrations (4319 and 5586 ng/mL), whereas those on DFX achieved superior outcomes and the lowest SF concentrations (3355 and 2152 ng/mL) in both years. Twenty-six patients from the 2019 cohort received no ICT for six years (from 2012 to 2018) and experienced extremely severe iron overload with SF levels ranging between 4481 and 16,000 ng/mL. Our findings prove a high prevalence of iron overload and suboptimal chelation outcomes in Syrian BTM patients, both prior to and during the ongoing armed conflict, despite the provision of free ICTs at HNTC. Poor adherence and older age of patients may explain the unfavorable outcomes of DFO and (DFO+DFP) regimens, whereas younger age and higher socioeconomic status may have contributed to the lowest SF and superior outcomes in patients on DFX. This study also demonstrates the crucial role of the National Thalassemia Centers, namely HNTC, in providing health services to BTM patients in times of peace and conflict.

Prevalence of Iron Overload and Chelation Therapy in patients of Thalassemia Major and Knowledge and Attitude of Population towards Iron Chelation Therapy in Sargodha, Pakistan

Background: Whether familial or sporadic, whatever the cause may be, among hereditary hematological disorders, thalassemia accounts for 4.5 out of 10,000 live births worldwide1. Among other complications that these patients have, magnitude of transfusion related iron overload ranges from 9.5%-18%2. Prevalence of post transfusion iron overload in Southeast Asia is much higher than Western world3. Aim: To measure the prevalence of iron overload and chelation therapy in patients of thalassemia major and knowledge and attitude of population towards iron chelation therapy in Sargodha, Pakistan. Methods: This was a cross-sectional study conducted at Rai Hospital, a private-sector hospital and Hilal-e-Ahmar Hospital in Sargodha. Total 390 patients of beta thalassemia major aged 1 month-20 years were included in the study. Data Records of 390 patients of beta thalassemia major, confirmed on hemoglobin electrophoresis admitted in the hospital from June 2021 to June 2022 were included. Data were collected on socio-demographics clinical and laboratory profile. Analysis was done in SPSS Results: The mean age of the participants was 8.79 years, and 51.2 % were males and 48.9 % were females. Iron overload was found in 85.64% % of patients. Highest figure was 18,666ng/ml. Mean serum ferritin level was 3815 ng/ml. 30.2% received regular chelation therapy; 35.3%was on irregular chelation therapy and in 34.3% it was not started yet. Significant factors associated with iron overload and lack of chelation therapy were highly constrained socioeconomic status, repeated and frequent transfusions, lack of knowledge of importance of chelation therapy and unawareness of complications of transfusion. Conclusion: Considering the prevalence and perils of disease itself and treatment related complications government should focus on establishing thalassemia centers nationwide to cater problems faced by these patients where trained doctors and paramedical staff can counsel them regarding disease prognosis and importance of iron chelation therapy in course of disease. Keywords: Prevalence, iron overload, thalassemia major, chelation therapy

Knowledge, Attitude, and Practice of Young Paediatricians About Chelation Therapyin Transfusion-Dependent Thalassemia Major Children

Objective: To determine the knowledge, attitude, and practice of young paediatricians about chelation therapy in transfusiondependent thalassemia major children.
 Study Design: KAP survey
 Place and Duration of Study: Six different hospitals in Rawalpindi and Islamabad Pakistan, from Jul 2019 to Jan 2020.
 Methodology: We study enrolled a sample of 98 doctors. The study included all residents (R1, R2, R3, and R4) and senior registrars of the six hospitals, while those on leave for any reason like maternity or others were excluded. A pre-validated questionnaire was used to collect the data.
 Results: Out of 98, maximum residents were of third-year (R3) 27(27.6%), followed by the second-year resident (R2) and senior registrar (SR) 19(19.4%). About 52(53.1%) residents reported that they did not have any thalassemia centre in their facility,with a maximum from Rawalpindi 65(66.3%). The study revealed that 61.2% study population had fair knowledge and attitude towards chelation therapy, while 22(22.4%) had poor and 16(16.3%) had satisfactory scores. The study revealed varied practices except for combination therapy, where 82.7% preferred it. The study showed a significant association between different categories of knowledge and attitude with professional levels, (p-value = 0.014).
 Conclusion: The majority had a fair knowledge and attitude towards chelation therapy, while the practice varies mostly,except for the maximum preferred combination therapy for chelation. The study further concluded that with an increase in professional experience, knowledge, attitude and practice improved towards better treatment.

Real-World Data on the Use of Luspatercept in Greek Patients with Transfusion Dependent Thalassemia

Introduction: The EMA/FDA-approved, erythroid maturation agent, luspatercept, has been shown to decrease transfusion burden in patients (pts) with transfusion-dependent thalassemia (TDT). Data on efficacy and safety for non-selected pts, not involved in clinical trials, are lacking. Aim: In this multicenter, retrospective cross-sectional study, real-world data from the use of luspatercept in TDT pts, managed in 9 major Thalassemia Centers in Greece are presented. Methods: Inclusion criteria included: TDT pts, having received luspatercept as per approved indications, treatment duration for at least 12 weeks. Data cut-off date was 30/06/2022. We estimated the quantity of blood (in cc of Packed Red Blood Cells -PRBC) received over 12 weeks. The following intervals were assessed post starting therapy: 1-12 weeks; 5-16 weeks; 13-24; the last 12 weeks of the observation period and 12 weeks post dose increase. The 12 weeks before starting treatment was considered as baseline. Changes in mean pre-transfusion hemoglobin (Hb), and in biochemical and other hematological parameters, were analyzed. Adverse events (AE) were recorded. Statistical analysis performed with RStudio v.3.6.2. Results: One hundred two pts (median age: 47 years range:25-67, sex: M:F/57:45) received Luspatercept every 21 days. Sixty-nine (67%) pts had transfusion burden >20 PRBC units/24 weeks, which was an exclusion criterion for the registration trial 'Believe'. Pts had variable genotypes, which included: β0/β0 (12 pts), β+/β0 (28 pts), β+/β+ (26 pts), β+/β++(11 pts), β++/β0 (10 pts), β++/β++ (1 pt), not available (14 pts). Luspatercept was administered for a median of 24 weeks (range: 12-70 weeks). The initial dose of luspatercept was 1 mg/kg and increased selectively up to 1.25 mg/kg based on tolerability and efficacy and according to guidelines. Main results of the study are shown in Table 1. A statistically significant (p<0.005) decrease in transfused PRBCs compared to baseline was observed in all 12-weeks’ intervals. There were no significant differences of transfused PRBCs between the initial interval of 1-12 weeks and neither any subsequent 12 weeks’ intervals nor the interval post dose increase. As dose increase was reserved for poor responders, the latter comparison suggests that higher doses are required in this group of pts to reach satisfactory results. There were no significant changes in mean pre-transfusion Hb compared to baseline. The percentage of pts who had a reduction in the transfusion burden of at least 33% from baseline increased with time and at the interval of 13-24 weeks was 49%. Only one pt (42years old, HBB:c.92+1G>T /HBB:c.*6C>G) became transfusion independent. A statistically significant (p<0.005) increase in uric acid and LDH was observed for the interval 1-12 weeks in comparison with baseline (mean: 5.8±1.7mg/dl vs 5.1±1.6mg/dl, 343±170mg/dl vs 232±99mg/dl, respectively). Similar difference was observed between the 13-24 weeks interval and baseline for uric acid and LDH and for the 24-36 weeks interval only for uric acid and platelets. (mean: 6.1±1.6 mg/dl vs 5.3±1.6mg/dl, 485x10^9±226x10^9/L vs 404x10^9±234x10^9/L, respectively). Fifty pts (49%) reported at least one AE. The most common AEs included: bone pain 36 pts (35.2%), fatigue 17 pts (16.7%), headache 9 pts (8.8%) and periorbital edema 7 pts (6,9%). Frequent urination, dizziness, hypertension, hyperuricemia, swelling at injection site, blurry vision, tearing, libido decrease, tachycardia, abdominal flatulence, insomnia, dyspnea were also reported. Treatment was discontinued in 36 pts (35%) after 19.3±8.1 weeks (range 12-48 weeks). Reasons for discontinuation included: no response (15 pts), adverse events (8 pts), patient's decision (6 pts), no response and adverse events (4 pts), adverse events not related to treatment (3 pts; spondylodesis, osteonecrosis of the hip during COVID19 infection and death due to COVID19 infection, respectively). Compared to the registration trial 'Believe', there were higher percentages of pts decreasing transfusion burden ≥33% but also of therapy discontinuation. Conclusions: Real world data on the use of luspatercept in TDT parallel results from the registration trial, showing heterogeneous and lasting efficacy and acceptable toxicity, despite including pts with different characteristics. Longer follow up and increased number of pts are required to validate these observations. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Outcomes of Patients with Haemoglobin Disorders in Cyprus: A Joined Report of the Thalassaemia International Federation and the Nicosia and Paphos Thalassaemia Centres (State Health Services Organisation)

Haemoglobinopathies, including thalassaemias and sickle-cell syndromes, are demanding, lifelong conditions that pose a significant burden to patients, families, and healthcare systems. Despite the therapeutic advances and the resulting improvements in prognosis accomplished in past decades, these patients still face important challenges, including suboptimal access to quality care in areas with developing economies, changing epidemiology due to massive migration flows, an evolving clinical spectrum due to ageing in well-treated patients, and limited access to novel high-cost therapies. We herein describe the organization of healthcare services for haemoglobinopathies in Cyprus—with particular focus on beta-thalassaemia, the most prevalent condition in this region—along with selected patient outcomes. This report aims at underscoring the fact that nationally funded and well-coordinated prevention and care programmes for chronic and complex conditions, such as haemoglobinopathies, with active involvement from patient organizations lead to effective disease control and excellent outcomes in survival, quality of life, social adaptation, and public health savings, and allow timely and effective responses to emerging crises, such as the COVID-19 pandemic. The Cyprus paradigm could therefore serve as a blueprint for the organization or adaptation of haemoglobinopathy programs in other countries since these disorders are still widely occurring.

Protein C and S levels in patients with Thalassemia intermedia

This study was conducted to assess the level of proteins C and S in patients with thalassemia intermedia from the Thalassemia Center in Erbil, Iraq. This study aimed to evaluate protein C and S levels in patients with β-thalassemia intermedia and correlate them to different clinical and laboratory parameters. This comprehensive descriptive case-control study was conducted in 2021. Twenty-three thalassemia intermedia patients were recruited. After the participants' demographic data were recorded, plasma levels of both proteins were measured. The acquired files were examined for the 23 patients studied, 48% of whom were female. The mean age of the patients was 16.32 years. The findings show that the proportion of protein C in males was greater than in females, while this percentage contrasts when compared with protein S (ranging between 89-99% and 85-96%, respectively). Concerning age, these two types of protein in children have more value compared to older ages. Only seven people had less than 1,000 ferritins, while the others had higher values. A decrease in proteins C and S was observed in the thalassemia intermediate compared to the control group. There was a significant relationship between the decreased protein C and S levels with splenectomy. Given the significant reduction in protein C and S levels among patients with thalassemia intermediate compared to the control group, there is an increased risk of thromboembolic events in patients with thalassemia intermediate.

Immune Status Against Hepatitis B Infection in Children with Thalassemia Major in Pakistan: A Single-Centre Study

Objectives: To assess the immunogenicity of the Hepatitis B Vaccine in children with thalassemia.&#x0D; Study Design: Prospective longitudinal study.&#x0D; Place and Duration of Study: Pak Emirates Military Hospital, Rawalpindi Pakistan from Aug 2018 to Jan 2019.&#x0D; Methodology: After ethical approval and informed consent, 150 diagnosed patients with thalassemia were selected from the Thalassemia centre at Pak Emirates Military Hospital Rawalpindi. The patients’ transfusion, vaccination history and clinical data were obtained. The patient's sera were tested for Anti-Hepatitis B surface antibodies (anti-HBs) by ELISA. The patients who showed seroprotection (anti-HBs titer&gt;10 IU/L) were taken as a case group.&#x0D; Results: Out of 150 patients, only 22% (33 patients) showed seroprotection (anti-Hbs titer&gt;10 IU/L). Children younger than four years had significantly positive anti-HBs (p-value=0.067) at a 5% significance level. Time since the last vaccination was also a significant factor, with the 3.76±3.072 years range exhibiting better protection (p=0.002).&#x0D; Conclusion: Protective Anti-HBs titer was reduced after the age of 4 years in our patients, so we recommend screening patients with thalassemia after four years to assess the need for a booster dose.

Role of serum hepcidin as a biochemical marker in children with Beta-thalassemia of iron status in Wasit Province Iraq

β-thalassemia is characterized by anemia and depending on the severity of the anemia. Hepcidin is a 25-amino-acid peptide generated by the liver, based on hypoxia, anemia, and iron storage. controls blood iron concentration and tissue distribution and regulates the body's iron hemostasis. To evaluate the usefulness of Serum Hepcidin level as a biochemical marker of iron status in children with β thalassemia major, β thalassemia Intermedia and its relation with serum ferritin level. A cross-section study which will involve 90 included 50 Thalassemia Major (TM) and 40 Thalassemia Intermedia (TI). Patients will be collected from the thalassemia center in Kut Hospital for Gynecology and Pediatrics, were randomly selected for this study. All patients child in both gender from (5-17 years). Enzyme-linked immunosorbent assay [ELISA] used for determination of Hepcidin, Abbott Architect C4000 And cobas c 111 analyzer used for the determination of Ferritin, Iron and Hemoglobin was measured by Sysmex XP-300. The study included both gender 62.2% were male and 37.8% were females, regarding male gender 57.1% had βTM and 42.9% had βTI while female gender 52.9% had B-thalassemia major and 47.1% had β-thalassemia Intermedia.

Exploring the Economic Aspects of β-Thalassemia in Jordan in 2019

Thalassemia are inherited hematological disorders considered among the most common genetic disorders worldwide, occurring more frequently in the Mediterranean Region. The WHO estimates that Beta-thalassemia affects 2.9% of the world’s population. In Jordan, the carrier prevalence rate of thalassemia is from 2-4%. Patients with thalassemia need a lifelong care, devastating their quality of life and imposing overwhelming psychological and financial burden on patients and their families. The Jordanian Ministry of Health (MOH) is the sole facility responsible for treating these patients from the pre-marital program until required medications regardless of their nationality. This study aimed to estimate the economic burden of thalassemia in Jordan in 2019. All 680 thalassemia patients admitted to thalassemia centers in Jordan and coming to out-patients’ clinics from July 1st to Aug 31st, 2019 are included. Data were collected using a pre-developed questionnaire from the electronic medical records. The economic burden was estimated from MOH perspective and societal perspective. The average annual cost was estimated to be 2,674 JOD for a single thalassemia Jordanian insured patient and 4,627 JOD for un-insured, while the non-Jordanian patient’ annual cost was estimated 4,751 JOD if insured and 6,651 JOD if un-insured. The total economic burden of thalassemia in Jordan in 2019 was estimated to be 2,148,741 JOD. Of this amount, 1,393,329 JOD was for Jordanians and 755,412 JOD for non-Jordanians. In conclusion, this high burden of thalassemia in Jordan requires adopting new controlling policies; pre-marriage counseling, education and raising awareness should be encouraged.

Hypothyroidism in Children with Β-Thalassemia at a Tertiary Hospital of South Punjab, Pakistan

Objective: To determine the prevalence of hypothyroidism among children with β-thalassemia major. Study Design: Cross-sectional study. Place and Duration of the Study: The Department of Hematological Disorder, Thalassemia and Bone Marrow Transplantation Centre, and Department of Biochemistry, Bahawal-Victoria Hospital, Quaid e Azam Medical College”, Bahawalpur, Pakistan from 1st January 2021 to 31st December 2021. Methodology: A total of 125 children of both genders (2 to 18 years) with diagnosis of β-thalassemia major were analyzed. Two ml blood sample under strict aseptic conditions was obtained from every study participant and sent to Institutional Pathological Laboratory for thyroid-stimulating hormone (TSH), T3, and T4. Results: In a total of 125 children with β-thalassemia major, 78 (62.4%) were male. Overall, mean age was 8.57±4.75 years while 57 (45.6%) children were aged between 6 to 10 years. Residential status of 84 (67.2%) children was rural. Parental consanguineous marriages were reported in 91 (72.8%) patients. Mean TSH, T3 and T4 levels were calculated to be 3.27±1.38 pmol/L, 4.71±0.75 pmol/L and 11.80±2.38 pmol/L respectively. Hypothyroidism was noticed in 38 (30.4%) children. Conclusion: Prevalence of hypothyroidism in children with β-thalassemia major was high. Early identification and management of hypothyroidism in β-thalassemia major may improve overall quality of life among these affected children Keywords: Β-thalassemia major, hypothyroidism, thyroid-stimulating hormone.

Assessment of Parents' Knowledge about Home Health Care Management to Children with Beta Thalassemia Major

Thalassemia is a hereditary condition that affects the formation of globin chains. Beta thalassemia is characterized by either a total loss of manufacture globin (β-thalassemia major) or a partial loss of globin manufacture (β-thalassemia minor). This type of inherited anemias is found in Mediterranean and Southeast Asian communities. Objective: Assessment of parents' knowledge regarding home health care management related to children with β-Thalassemia Major. Methodology: A descriptive study design was carried out at Thalassemia Center in Al-Najaf City during the periods 25 ͭͪ February 2021 to 15 ͭͪ March 2022. Non-probability (purposive) sample of (35) parents were selected from thalassemia center (22 mothers and 13 fathers). Results: The finding shows that 77.1% of parents are resident in urban. The monthly income, over than half (54.3%) of parents consider their income to be barely sufficient. The sources of information about disease among parents; (88.6%) of parents are getting information from medical team. The parents are demonstrating poor knowledge level in most domains about home health care management of child with beta thalassemia major. Conclusion: The current study shows that there is a significant inadequacy in the parents' knowledge of the child with beta thalassemia major. Recommendation: Providing educational guidelines, posters, pamphlets and manuals about thalassemia and should be available at each parents in wards and encourage parents to get use from them.

THE CORRELATION OF β/α MRNA RATIO WITH CLINICAL AND HEMATOLOGICAL PARAMETERS IN PATIENTS WITH β-THALASSEMIA SYNDROME

Background: Thalassemias are a group of genetically transmitted blood diseases characterized by defects in the production of α- or β-chains of hemoglobin called α-thalassemia and β-thalassemia, respectively. One of the common features of β-thalassemia is ineffective erythropoiesis because of the imbalance of globin chain production, which result in increased apoptosis during erythroblast maturation. Objective: To evaluate the ß/α globin mRNA ratio in patients with ß-thalassemia syndrome and to correlate the ß/α ratio with hematological and clinical condition of the patients. Methods: Thirty-five patient samples were collected from Thalassemia Centre of Ibn Al-Balady Hospital; 18 patients with β-thalassemia major and 17 patients with β-thalassemia intermedia. The patients were randomly selected regarding sex, whereas their age ranged from 3 to 17 years. Along with those samples, twenty control leftover samples that were the remaining of samples collected for laboratory investigation, were taken from Al-Kadhimiya Pediatric Hospital, and were age and sex matched with the patients group. The α and β globin chain ration were calculated by the real-time reverse transcription-polymerase chain reaction (qRT-PCR). The β/α -globin mRNA ratio of the samples was measured by the 2−ΔΔCT method. Results: Analysis of the β-globin/α-globin mRNA ratio showed that disease severity increased with a reduction of the ratio. There was a highly significant difference in α level, ß level and ß/α ratio among studied groups with a p value of (p &lt; 0.001). The highest level was in control group, followed by that in β-thalassemia intermedia and the lowest was in β-thalassemia major. Conclusion: The severity of ß/α globin chain imbalance showed a significant and negative correlation with the mean corpuscular volume and there was no significant correlation between the ß/α ratio and markers of erythropoiesis in ß-thalassemia major and ß-thalassemia intermedia patients. The ß/α ratio was a good tool for diagnosis in ß-thalassemia major and ß-thalassemia intermedia as compared to control group with high sensitivity and specificity. A ß-chain gene expression was the lowest in ß-thalassemia major followed by ß-thalassemia intermedia as compared to control group. Keywords: Thalassemia, ß/α -globin mRNA ratio Citation: Yousif MH, Al-Mamoori HS. The Correlation of β/α mRNA Ratio with Clinical and Hematological Parameters in Patients with β-thalassemia Syndrome. Iraqi JMS. 2022; 20(1): 139-145. doi: 10.22578/IJMS.20.1.18

The association between iron over load and tanner stage retardation in the females with B-thalassemia major in Thalassemia center of Diwaniyah maternity and children teaching Hospital.

Despite optimal therapy of patients with B- thalassemia major included regular blood transfusion program and iron chalation agents helped by increasing survival of these patients but remained major problem in adolescent of these patients such as growth failure and hypogonadisim. &#x0D; Aim of study: To determine the association between iron over load and tanner stage retardation among female patients with B- thalassemia major in Thalassemia center of Diwaniyah maternity and children teaching Hospital.&#x0D; Methods: The current study was carried out on all female patients diagnosed ?-thalassemia major on the base of the blood investigations (peripheral blood counts and hemoglobin electrophoresis),with their age range from 13years to 16 years who registered in Thalassemia center of Diwaniyah maternity and children teaching hospital in Al- Diwaniyah Governorate, Republic of Iraq. The Data collection was carried out during the period from the 1st of April of 2016 to 30th of December of 2016. They were studied for determining the association between iron over load and tanner stage retardation among female patients with B- thalassemia major.&#x0D; The following data were collected from the patients: &#x0D; Name, age, address ,age of diagnosis of thalassemia, number of blood transfusion per year, types of chelating agent.&#x0D; In the physical examination, the patients were assessed for weight, height, Tanner stages and body mass index(BMI) which recorded.&#x0D; &#x0D; Ferritin value was used to assess iron load, pelvic ultrasound was checked to assess the size of uterus and both ovaries.&#x0D; &#x0D; Results: Total numbers of B- thalassemia major female patients are 31 patient, aged 13-16 years (mean age: 14.13 ±1.20) . Age of patients at time of diagnosis of B- thalassemia major range from 0.17 to 5 year with Mean ± SD(1.40 ±1.30). Frequency of Blood transfusion (time/Year) range from 6 to 33 time/Year with Mean ± SD(16.68 ±4.98). Level of serum ferritin of the patients was ranged from 913-12000 ng/ml with Mean ± SD (4963.60 ±3580.39).&#x0D; Tanner stage I was predominant accounting for 87% whereas stage II and III accounted for 10% and 3% respectively. There was no significant correlation between Tanner stage and age of patient and also no significant correlation with age at time of diagnosis (P&gt;0.05). There was a significant negative correlation between frequency of blood transfusion and Tanner (r=-0.385, P= 0.045), so that the higher the frequency of transfusion, the lower the tanner stage is. No correlation was found between the dose of chelating agent and Tanner stage (P=0.599). Height and weight of patients were significantly correlated with Tanner stage (P=0.028 and P=0.007, respectively). No significant correlation was found between serum ferritin and Tanner stage (P=0.444). There was a significant correlation between Uterus size, ovarian size and Tanner stage (P=0.007and P=0.007, respectively).&#x0D; Conclusion: These results showed that no significant correlation between tanner stages retardation and iron overload in female patients with ?-thalassemia major measured by serum ferritin. Because of inflammation falsely increase serum ferritin or because of the relationship between body iron and level of serum ferritin is not always within the linear range especially in condition of inflammation or tissue damage. So that serum ferritin level is not a reliable indicator of total body iron stores in patients with thalassemia major, therefore; we needed another indicator to measure total body iron stores in patients with thalassemia major such as the liver iron concentration.

Comparative study of oxidative status and some biochemical parameters in subjects suffered of intermediate and major Thalassemia

In the β-thalassemia’s, oxidative stress, resulting from chronic hemolysis, globin chain imbalance, iron overload and depleted antioxidant defenses, likely contributes to cell death, organ damage, anemia, hypoxia and inflammation. Between November 2020 and June 2021, the study assessed adults aged (25-35 years) attending to Hiwa Cancer Hospital/ Sulaimaniah Thalassemia and congenital blood disorders center/ Iraq: 60 patients with HbE β-thalassemia, 30 β-thalassemia major, 30 β-thalassemia intermediate and 30 control subjects. ferritin were measured as sources of oxidants; plasma antioxidants: Glutathione Reductase (GR) and Oxidative stress-induced growth inhibitor 2 (OSGIN2) , plasma D-dimer assessed thrombosis status and serum C-reactive protein assessed inflammation, the results showed increased in the levels of ferritin, plasma D-dimer and CRP in both β-thalassemia major and β-thalassemia intermediate (2789±789 ; 2657±725.8 ng/ml) , (175.4±54.02; 188.7±62.01 ng/ml) and (15.6±2.6; 13.3±3.1 mg/l) compared to control group (178.7±58.9 ng/ml) , (79.8±34.8 ng/ml) and (2.3± 0.7 mg/l) respectively. Whereas decreased in the levels of GR and OSGIN2 (38.4±12.7; 35±8.8 pg/ml) and (58±18.3; 78±20.5 mg/dl) compared to control group (96±17.3 pg/ml) and (156±65.6 mg/dl ) respectively.

P1517: REAL-WORLD COMPLICATION BURDEN AND DISEASE MANAGEMENT IN TRANSFUSION-DEPENDENT ADULTS WITH ΒETA-THALASSEMIA (Β-THAL) IN GREECE: FINAL RESULTS OF THE EPIDEMIOLOGICAL CROSS-SECTIONAL ULYSSES STUDY

Background: Despite improved prognosis, patients with transfusion-dependent β-thal commonly experience treatment and disease complications. Aims: To assess the prevalence and severity of treatment and disease complications, capture disease management, and identify predictors of complications in a representative sample of patients with transfusion-dependent β-thal in routine settings in Greece. Methods: ULYSSES is an epidemiological, multicenter, retrospective cross-sectional study of adults diagnosed with β-thal ≥12 months before enrollment who received ≥6 red blood cell (RBC) units (excluding elective surgery) with no transfusion-free period ≥35 days in the 24 weeks before enrollment. Hemoglobinopathies S/β- and α-thalassemia were excluded. Primary data were collected at a single visit and through chart review. Results: From Oct 21, 2019 to June 15, 2020, a total of 201 eligible patients were enrolled by 12 major thalassemia centers; 64.2% were female, median age was 45.7 years (interquartile range [IQR], 40.2–50.5; 75.6% >40 years), mean (standard deviation [SD]) time since diagnosis was 42.9 (7.8) years.Overall, 44.3% were β+β+, 36.8% β+β0, 13.4% β0β0, and 5.5% carried β+, δβ-Sicilian, Corfu δ0β+, Turkish (δβ)0, and hemoglobin Lepore combinations. The most common β-globin mutations were IVS1-nt110 G>A (63.7%), Codon 39 C>T (25.4%), and IVS1-nt6 T>C (22.9%). Median (IQR) age at diagnosis and RBC transfusion initiation was 0.8 (0.4–2.8) and 1.3 (1.0–5.0) years, respectively. During the 48 weeks prior to enrollment, patients received a mean (SD) of 34.2 (9.5) RBC units from a median (IQR) of 23.0 (18.0–28.0) RBC transfusion events. Before enrollment, all patients had received iron chelation therapy (ICT), started at a median (IQR) age of 6.4 (3.2–12.9) years (median [IQR] exposure 35.6 [30.0–40.0] years), and 53.2% had received other therapies, including folic acid (48.3%); 53.2% had a splenectomy at a median (IQR) age of 22.0 (14.0–29.0) years. From diagnosis to enrollment, patients developed 1443 cumulative complications (median 6 [range, 1–55]; 585 ongoing at enrollment; 19.6% [237/1211] known Grade ≥3). Disease-related complications related to β-thal were experienced by all patients (total 1089 [median 5 (range, 1–21)]; 22.1% were Grade ≥3). Over half of patients (53.2%) experienced complications related to treatment (total 354; [median 1 (range, 0–35)]; 13.0% Grade ≥3; Figure), of which 43.4% (n=273), 25.4% (n=73), and 2.0% (n=8) were related to RBC transfusions, ICT, or other treatments, respectively. Of patients 18–40 years, 36.7%, 30.6%, and 16.3% experienced ≥1 treatment-related, RBC transfusion,or ICT complication, respectively, compared with 58.6%, 48.7%, and 28.3% of those >40 years. The 48-week pre-enrollment hospitalization rate due to disease or treatment complications was 0.076 per patient-year (95% confidence interval [CI], 0.045–0.128). Medical/surgical history (odds ratio[OR], 5.16; 95% CI, 1.91–13.92; P=0.001), splenectomy (OR, 2.86; 95% CI, 1.16–7.02; P=0.022), and >24 transfusion events in 48 weeks prior to enrollment (OR, 2.78; 95% CI, 1.15–6.74; P=0.023) were associated with increased odds for developing treatment-related complications. In contrast, splenectomy was associated with lower odds (OR, 0.27; 95% CI, 0.08–0.89; P=0.031) of having either treatment- or disease-related complications. Image:Summary/Conclusion: Real-world data generated by ULYSSES underscore the substantial complication burden of patients with transfusion-dependent β-thal routinely managed in Greece, which worsens with advanced age. †First and second author have contributed equally.

Identification of osteopenia and osteoporotic changes in pediatric thalassemia patients at thalassemia center, Misan city, Iraq; An intervention study

Background: Thalassemia syndrome is a heterogeneous group of hereditary disorders affecting the synthesis of globin chains of adult hemoglobin's, leading to ineffective erythropoiesis, hemolysis, and moderate to severe anemia. To identify the incidence of osteopenia and osteoporosis and it is relation to some of the probable risk factors of decreasing BMD among thalassemia patients attended Misan thalassemia center in Misan city in Iraq.&#x0D; Methods: A randomized cross-sectional study, applied through a period from September 2020 to September 2021, on 50 thalassemia patients attended thalassemia Center Amarah, Misan, Iraq. 24 were males and 26 were females, we divided them in to two groups according to age (10-14) years, (&gt;14-18) years. They were scanned for bone mineral density (BMD) at lumbar spine.&#x0D; Results: 90% of patients had reduction in BMD patients mostly among THM patients. 40% had positive family history of thalassemia, Vitamin D3 level were low in (80%) of patients &amp; DEXA studies were mostly between [(-1) -(-2.5)] before treatment that slightly improved after therapy in ranges of osteopenia but not in osteoporosis which increase severity as well.&#x0D; Conclusions: Most thalassemia patient had severe anemia, corrected by frequent blood transfusion are complicated by increasing serum ferritin level and decreasing level of vitamin D3 in association with reduction in bone density mass in ranges of osteopenia and osteoporosis which correlates positively with increasing ages, early age at diagnosis and female gender this altered bone mass density require family awareness for better nutrition and optimum medical therapy and compliance to improve outcomes. &#x0D;

The Effect of Long-Term Iron Chelator Therapy on Serum Levels of Hepcidin and Ferritin in Patients with Thalassemia Major and Intermediate.

Serum hepcidin is a good predictor of iron overload compared with serum ferritin. However, serum hepcidin levels may change under different conditions. The current study aims to determine the role of long-term iron chelator therapy on serum levels of hepcidin and ferritin in patients with thalassemia major (TM) and intermediate (TI). In this cross-sectional study 91 patients with thalassemia TM and TI, who referred to the thalassemia center were chosen. The serum levels of hepcidin and ferritin were measured after two years of iron chelator therapy by ELISA and ECL methods, respectively. The patients' demographic information was extracted from their records. After treatment with iron chelator, ferritin levels decreased in 44 patients (48.4%), and increased in 47 patients (%51.6). Median serum levels of hepcidin decreased in all patients (%100). Also, there was a significant association between serum levels of hepcidin and ferritin (p value = 0.034). Furthermore, while a significant difference was observed between ferritin changes (p = 0.01), no difference was found between changes in hepcidin based on the type of iron chelator (p value = 0.94). Increased levels of hepcidin and ferritin in β-thalassemia patients are significantly ameliorated by iron chelator.

Impact of an educational program on parents' knowledge about chelation therapy &amp; nutrition of their children with beta thalassemia major

The study aimed to determine the effect of an educational program on parents' knowledge about chelation therapy, and nutrition of their children with beta thalassemia major. A quasi experimental study was carried out at Thalassemia Center in Al-Najaf City during the periods 25 ͭ ͪ February 2021 to 15 ͭ ͪ March 2022. Non-probability (purposive) sample of (70) parents were selected from thalassemia center (38 mothers and 32 fathers).The result of the study findings indicate that education program about home health care management was highly effective on parents’ knowledge in the study group evidenced by high significance associated with “Greenhouse-Geisser” correction at p-value=0.001. Also there is a significant relationship between parents’ knowledge with regard to affected father with disease at p-value= .049.

Effectiveness of an Educational Program on Parents' Knowledge about Home Health Care Management to Children with Beta Thalassemia-Major at Thalassemia Center in Al-Zahra Teaching Hospital for Maternity and Children in Al-Najaf City

Background Thalassemia is a hereditary condition that affects the formation of globin chains. Children with βeta-thalassemia major have a complete absence of globin production. βeta thalassemia- major is a severe type of disease that require life-long blood transfusions for survival. Objectives: To evaluate the effectiveness of an educational program on parents' knowledge regarding home health care management related to children with Beta Thalassemia-Major Methodology: A quasi experimental study was carried out at Thalassemia Center in Al-Najaf City during the periods 25 February 2021 to 20 March 2022. Non-probability (purposive) sample of (70) parents were selected from thalassemia center (38 mothers and 32 fathers). Results: The study findings show that there are high significant difference in overall main domains relating parents' knowledge of beta-thalassemia major between pre and post-tests 1&amp;2 in the study group. In addition there is a statistical relationship between parental knowledge with regard to their age. Also there is high statistical significant relationship during parents’ knowledge with regard to their educational level Conclusion: The study finds that the efficacy of an educational program to improving parents' knowledge of home health care management for children with β-Thalassemia Major is high Keyword: Educational Program, Beta thalassemia, Children, AL-Najaf City