Transfusion-dependent Thalassemia Patients Research Articles

Role of Transient Elastography in Pediatric Transfusion Dependent Thalassemia Patients from Lower Socioeconomic Strata and its Correlation with Serum Ferritin: A Cross-Sectional Study

Role of Transient Elastography in Pediatric Transfusion Dependent Thalassemia Patients from Lower Socioeconomic Strata and its Correlation with Serum Ferritin: A Cross-Sectional Study

Exploring alterations of gut/blood microbes in addressing iron overload-induced gut dysbiosis and cognitive impairment in thalassemia patients

Iron overload causes cognitive impairment in thalassemia patients. The gut-brain axis plays an important role in cognitive function. However, the association between gut/blood microbiome, cognition, and iron burden in thalassemia patients has not been thoroughly investigated. We aimed to determine those associations in thalassemia patients with different blood-transfusion regimens. Sixty participants: healthy controls, transfusion-dependent thalassemia (TDT) patients, and non-transfusion-dependent (NTDT) patients, were recruited to evaluate iron overload, cognition, and gut/blood microbiome. TDT patients exhibited greater iron overload than NTDT patients. Most thalassemia patients developed gut dysbiosis, and approximately 25% of the patients developed minor cognitive impairment. Increased Fusobacteriota and Verrucomicrobiota with decreased Fibrobacterota were observed in both TDT and NTDT groups. TDT patients showed more abundant beneficial bacteria: Verrucomicrobia. Iron overload was correlated with cognitive impairment. Increased Butyricimonas and decreased Paraclostridium were associated with higher cognitive function. No trace of blood microbiota was observed. Differences in blood bacterial profiles of thalassemia patients and controls were insignificant. These findings suggest iron overload plays a role in the imbalance of gut microbiota and impaired cognitive function in thalassemia patients. Harnessing probiotic potential from those microbes could prevent the gut-brain disturbance in thalassemia patients.

Elevated Plasma Atherogenic and Triglyceride-Glucose Indices: Markers of Cardiovascular Risk in Transfusion-Dependent Thalassemia

Background Transfusion-dependent thalassemia (TDT) is an autosomal recessive disorder characterized by defective hemoglobin synthesis, leading to severe complications such as iron overload and multi-organ dysfunction. This study aims to elucidate the distinctive clinical and biochemical profiles of TDT patients compared to healthy controls, with an emphasis on cardiovascular risk assessment using novel markers such as the Plasma Atherogenic Index (PAI) and Triglyceride-Glucose (TyG) index. Methods This cross-sectional study included 32 TDT patients and 36 healthy controls, matched for age and gender. Comprehensive demographic, laboratory, and imaging data were collected and analyzed. TDT patients were further stratified based on cardiac involvement and ferritin levels. Key assessments included hemoglobin levels, liver enzymes, lipid profiles, and cardiac imaging. The PAI and TyG index were calculated to evaluate cardiovascular risks. Statistical analyses were performed using SPSS 27.0, employing Student’s t-test, Mann–Whitney U test, and Pearson chi-square test as appropriate. Results No significant differences in basic demographic parameters were observed between groups; however, TDT patients exhibited significant clinical and laboratory differences. Notably, these patients had lower hemoglobin levels, higher platelet counts, elevated liver enzymes (ALT and AST), and markedly increased ferritin levels. Lipid profiles were significantly altered, with lower levels of total cholesterol, HDL, and LDL but elevated triglycerides. Importantly, the PAI was significantly higher in TDT patients, suggesting an increased atherosclerotic risk. Subgroup analysis revealed that patients with cardiac involvement had worse metabolic profiles, higher TyG indices, and prolonged QT intervals, indicating heightened cardiovascular risk. As the iron burden increases, the TyG index and PAI may lose their sensitivity in distinguishing between varying levels of iron overload, suggesting that their effectiveness plateaus beyond a certain threshold of iron accumulation. Conclusion TDT patients show significant hematological and metabolic deviations, including elevated cardiovascular risk markers like PAI and TyG index. As iron burden increases, these markers lose discriminative power, and cardiac involvement escalates rapidly once a critical iron threshold is surpassed, as supported by studies showing a non-linear relationship between iron load and cardiac complications. Comprehensive cardiovascular risk assessment and tailored management are essential for these patients. Future studies should focus on tracking cardiovascular risk progression and the effects of targeted interventions.

Combined effects of exercise and nutritional interventions on sarcopenia and its associated quality of life in transfusion-dependent thalassemia patients: a single-arm, open-label study

Combined effects of exercise and nutritional interventions on sarcopenia and its associated quality of life in transfusion-dependent thalassemia patients: a single-arm, open-label study

Assessment of growth retardation among transfusion-dependent Thalassemia patients in Peshawar, Pakistan

Assessment of growth retardation among transfusion-dependent Thalassemia patients in Peshawar, Pakistan

Outcomes of late endocrinologic evaluation in adult patients with thalassemia major: case series

AThalassemia is a group of inherited disorders characterized by the reduced or absent synthesis of the globin chains that make up hemoglobin. Transfusion-dependent thalassemia (TDT) is the most severe form, which requires lifelong transfusion. Complications related to the heart, liver and endocrine glands caused by the accumulation of excess iron in different organs due to transfusions are seen in adult patients. Of these complications, endocrine gland complications are widespread in adult patients. Hypogonadism is the most commonly reported endocrine complication, which affects 70-80% of thalassemia major patients. In this case series, we will present three female patients, aged 37, 18 and 27, who were followed up with the diagnosis of TDT and who underwent endocrinological evaluation in adulthood. We aim to emphasize that the diagnosis of hypogonadotropic hypogonadism and growth hormone (GH) deficiency was made late because the endocrinological evaluation of these patients was performed at an adult age, and we discussed the consequences of this. The survival of TDT patients has improved significantly in the last decade due to the introduction of transfusion, oral iron chelation therapies, and bone marrow transplantation, and these patients live into adulthood. Therefore, endocrinologic evaluation should be performed in pre-pubertal and pubertal periods. Early recognition of endocrine complications and early initiation of treatment are important to prevent irreversible sequelae.

Serum ferritin is a risk factor for pulmonary dysfunction in young patients with transfusion-dependent thalassemia

Research into the pulmonary function of patients with transfusion-dependent thalassemia (TDT) is limited, with existing studies presenting conflicting results. We carried out a retrospective study involving 140 patients with TDT. The mean patient age was 8.7 ± 3.2 years, with a median serum ferritin (SF) level of 3791.4 ng/ml (IQR: 2424.1–5733.3 ng/ml). Pulmonary function abnormalities were detected in 46.43 % (65 out of 140) of patients, primarily manifesting as diffusion dysfunction (26.43 %), followed by ventilatory dysfunction (5.0 %), and mixed pulmonary dysfunction (15.0 %). A serum ferritin level above 2500 ng/ml significantly correlated with the occurrence of these abnormalities(OR = 3.187, 95%CI:1.312–7.741, P = 0.010), while higher hemoglobin concentrations demonstrated a protective effect (OR = 0.966, 95%CI: 0.943–0.989, P = 0.004). Our study highlights diffusion dysfunction as the most prevalent type of pulmonary function abnormalities in TDT patients. Furthermore, it establishes a correlation between elevated serum ferritin levels and pulmonary dysfunction.

Assessment of Cardiac, Hepatic and Pancreatic Iron Overload in Transfusion Dependent Thalassemia Patients Using T2* Magnetic Resonance Imaging

Assessment of Cardiac, Hepatic and Pancreatic Iron Overload in Transfusion Dependent Thalassemia Patients Using T2* Magnetic Resonance Imaging

Study of platelet activation, hypercoagulable state, and pulmonary hypertension in patients with transfusion-dependent beta-thalassemia

Abstract: BACKGROUND: Thalassemic patients require lifelong blood transfusions, which can lead to complications such as pulmonary arterial hypertension. The pathogenesis involves hypercoagulability, in which researches on coagulation abnormalities in this regard are limited. OBJECTIVES: The aims of the study was to investigate the mechanism of hypercoagulability and pulmonary hypertension in transfusion-dependent thalassemic patients and compare it with healthy controls. PATIENTS MATERIALS AND METHODS: This case–control analysis enrolled 50 transfusion-dependent thalassemia patients and 50 healthy controls. Complete blood counts, liver function tests, coagulation markers (P-selectin, protein C, antithrombin III, and fibrinogen), serum ferritin, and transthoracic echocardiography were performed, and blood transfusion/chelation history and splenectomy status were recorded. RESULTS: Thalassemia patients revealed severe anemia, leukocytosis, thrombocytosis, significantly elevated serum ferritin (1957.50 ± 2455.05 g/L), elevated liver enzymes serum glutamic oxaloacetic transaminase (22.01 ± 9.89 U/L), serum glutamic pyruvic transaminase (22.70 ± 9.78 U/L) in comparison to controls, and mean serum P-selectin was significantly higher in thalassemic patients (100.48 ± 53.29 ng/mL). Mean serum antithrombin-III and protein C were significantly lower in thalassemic patients (89.27 ± 16.08 units/h, 86.04 ± 25.21 μg/mL) in comparison to controls. CONCLUSIONS: Transfusion-dependent thalassemia is characterized by severe anemia and splenomegaly, leading to complex hemodynamic changes with evidence of platelet activation, hypercoagulable state, liver injury, and increased atherosclerosis. It induces pulmonary artery thrombosis contributing to the development of pulmonary artery hypertension.

Role of Quercetin Supplementation on Iron Parameters in Blood Transfusion-Dependent Thalassemia Patients

Background: Thalassemia is a group of inherited blood disorders that affect the production of hemoglobin, a protein in red blood cells that carries oxygen throughout the body. Iron overload is a condition in which the body absorbs and stores too much iron. In addition to repeated blood transfusions, increased gastrointestinal tract (GIT) iron absorption plays an important role in iron overload with thalassemia. Quercetin, a common flavonoid present in fruits and vegetables, exhibits diverse biological effects. Objective: To assess the effect of quercetin on iron overload parameters in blood transfusion-dependent thalassemia patients (TDT). Methods: A randomized, double-blind, placebo-placebo group-led study was conducted on 110 TDT patients, more than 12 years of age, who were supplemented with either quercetin or a placebo capsule daily (500 mg) for 3 months. A blood sample was obtained for laboratory parameters at baseline and at the end of 3 months. Results: At the baseline time of the study, the demographic features and iron overload parameters of patients and the placebo group were not statistically different, while after three months of supplementation, there was a significant decrease in levels of serum iron, UIBC, serum ferritin and ferritin saturation rate, and a significant increase in TIBC in the patients compared with the placebo group. Conclusions: The study shows the significant role of quercetin on iron overload parameters in blood transfusion-dependent thalassemia patients.

Genotype Distribution and Clinical Characteristics of Thalassemia Patients Needing Transfusion in Yangjiang, Western Guangdong

Plain Language SummaryThis study is a retrospective research that investigates the genotype distribution and iron metabolic imbalance in thalassemia patients requiring blood transfusion. Eighty-four thalassemia patients needing transfusion were enrolled in the study and underwent genotype analysis. Among these patients, 56 were transfusion-dependent and 28 were non-transfusion-dependent. Of the 56 transfusion-dependent patients, 48 were observed for 3 years, and their iron overload status was analyzed in this study. Our research found that among the 84 thalassemia patients needing transfusion, there were six types of α-thalassemia deletions and nine types of β-thalassemia mutations. Among the 56 transfusion-dependent patients, three types of α-thalassemia genotypes and 15 types of β-thalassemia genotypes were identified. Among the 48 transfusion-dependent thalassemia patients observed for 3 years, 40 patients exhibited iron overload with SF levels exceeding 1,000 ng/mL. The recent SF levels were lower than those 3 years ago. Our study found that β-thalassemia is the most common type of transfusion-dependent thalassemia. Standard blood transfusion and iron chelation therapy are necessary for transfusion-dependent thalassemia patients. While some patients show a reduction in SF levels after 3 years of treatment, there are still individuals who exhibit elevated levels necessitating ongoing management.

A Comparison of Pain Before and After Transfusion in Adult transfusion-dependent thalassemia (TDT) Using BPI-SF.

Background Pain is a complication in patients with transfusion-dependent thalassemia (TDT). There are several mechanisms underlying pain in people with thalassemia and low hemoglobin at the end of the transfusion cycle was the most etiology. Pain can develop into chronic pain and interfere with the quality of life. The Brief Pain Inventory Short Form (BPI-SF) can help identify pain in people with TDT. The present study aimed to compare pain before and after transfusion in adult TDT patients. Methods It was an analytical observational study using a cross-sectional design on adult TDT patients with pain who came to the Haemato-Oncology Clinic of Dr. Hasan Sadikin Hospital Bandung. This study was conducted from December 2020 to July 2021. All subjects were assisted in filling out the Indonesian version of the BPI-SF questionnaire hemoglobin levels were examined and before and after transfusion, then paired test analysis was performed using the Wilcoxon Test. Results This study is conducted on 60 adult TDT patients with symptoms of pain. The median value of pain intensity and pain interferes with life obtained from the Indonesian version of the BPI-SF score after transfusion decreased significantly compared to before transfusion (NRS 5 vs. 0 and 2.8 vs. 0; p=0.0001). Conclusion There is a significant difference in pain intensity and pain interfere with life in adults with TDT before and after transfusion. It is necessary to carry out pain assessments for thalassemia patients.

Assessing Psychological Disorders in Turkish Adolescents with Transfusion-Dependent Thalassemia.

We investigated depression and anxiety levels and related psychological disorders in adolescents with transfusion-dependent thalassemia (TDT) in this study. The study was conducted in two pediatric hematology outpatient clinics and included adolescents with TDT (14.8 ± 2.4 years, n = 40) in the study and compared them with the healthy age-matched control group (14.3 ± 2.3 years, n = 62). The Turkish version of the Revised Child Anxiety and Depression Scale (RCADS) was used to determine depression, anxiety, and related psychologic disorders (obsession, panic disorder, social phobia). Depression, anxiety, obsession, panic disorder, and social phobia scores were significantly higher in the patient group compared with the control (all p < 0.05). Ferritin levels were positively correlated with total depression, general anxiety, separation anxiety, and social phobia scores, but transfusion frequency and young age were the confounding factors. Patients in early adolescence and those who require more frequent blood transfusions are at higher risk of developing psychological disorders; routine screening for mood disorders should be warranted. Serum ferritin level may be a good warning indicator for early recognition of psychologic disorders in TDT patients.

Evaluation of microstructural changes in the brain in transfusion dependent thalassemia patients with advanced magnetic resonance imaging techniques

PurposeTransfusion-dependent thalassemia (TDT) is associated with iron accumulation in the body and an increased tendency for thrombosis. With the increased life expectancy in these patients, the detection of neurocognitive complications has gained importance. This study investigates the microstructural changes in TDT patients using advanced diffusion MRI techniques and their relationship with laboratory parameters.MethodsThe study included 14 TDT patients and 14 control subjects. Tract-based spatial statistics (TBSS) were used to examine differences in DTI parameters such as fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in thalassemia patients using multi-shell DWI images. The mean kurtosis (MK) difference was investigated using diffusion kurtosis imaging. Fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC) differences were examined using fixel-based analysis. In the patient group, correlative tractography was used to investigate the relationship between DTI parameters and platelet (PLT) and ferritin levels.ResultsIncrease in RD and MD was observed, particularly in the white matter tracts of the corona radiata in patient group. Additionally, an increase in AD was detected in a limited area. Correlative tractography in thalasemia patients showed a positive correlation between increases in RD, MD, and AD with PLT and ferritin. Fixel-based analysis demonstrated a dispersed distribution in white matter fibers, with a more pronounced decrease in FD, FC, and FDC in the internal capsule.ConclusionThere is widespread involvement in the white matter and fiber tracts in thalassemia patients, which is highly correlated with thrombotic parameters.

Cognitive debriefing and the validity of the Malay EQ-5D-3L in transfusion-dependent thalassemia patients from Sabah, Malaysia

Cognitive debriefing and the validity of the Malay EQ-5D-3L in transfusion-dependent thalassemia patients from Sabah, Malaysia

Association of serum ferritin trends with liver enzyme patterns in β-thalassemia major: A longitudinal correlational study.

β-Thalassemia major patients require lifelong blood transfusions, leading to iron overload and liver injury. This study examines the longitudinal association between serum ferritin and liver function over 5 years in pediatric patients. This retrospective study included 582 transfusion-dependent thalassemia patients aged 1-18 years. Serum ferritin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and albumin were measured annually. Correlation and linear regression analyses assessed associations between ferritin trajectories and liver enzymes. Mean ferritin rose from 1820 ± 960 ng/mL at baseline to 4500 ± 1900 ng/mL at year 5, indicating worsening iron overload. AST and ALT levels also steadily climbed over follow-up, whereas albumin declined slightly. Ferritin correlated positively with AST (r = 0.675, P < 0.01) and ALT (r = 0.607, P < 0.01), but not with albumin (r = -0.143, P = 0.153) annually. The regression interaction term showed within-patient ferritin increases over time were independently associated with escalating AST and ALT (P < 0.05), after adjusting for confounders. Rising ferritin levels predict progressive liver injury in regularly transfused pediatric thalassemia patients. Tighter control of iron overload may help preserve hepatic function.

A Compact Differential Dynamic Microscopy-based Device (cDDM): An Approach Tool for Early Detection of Hypercoagulable State in Transfusion-Dependent-β-Thalassemia Patients.

β-Thalassemia especially transfusion-dependent thalassemia (TDT) associates with a hypercoagulable state, which is the main cause of thromboembolic events (TEE). Plasma viscosity and rheological parameters could be essential markers for determining hypercoagulable state in β-thalassemia patients. The traditional methods for measuring viscosity are often limited by large sample volumes and are impractical for routine clinical monitoring. The compact differential dynamic microscopy-based device (cDDM), an optical microscopy for quantitative rheological assessment, was developed and applied for prognosis of the hypercoagulable state in β-TDT with and without splenectomy. The device was performed plasma viscosity measurement using low plasma volume (8 μL) and revealed a value as modulus of complex viscosity |η(ω)| in 7 min. We also parallelly demonstrated the correlation of the viscosity and related-coagulable parameters: complete blood count, prothrombin time (PT), activated partial thromboplastin time (APTT), protein C (PC), protein S (PS), CD62P and CD63 expression, and platelet aggregation test. The thalassemia plasma exhibited a higher value of |η(ω)| than healthy plasma, which can represent a different viscoelastic property among the groups. Even all related-coagulable parameters indicated hypercoagulable state in both nonsplenectomies and splenectomies β-TDT patients when compared to control, only high platelet numbers significantly correlated to high plasma viscosity in the splenectomy group. However, the other coagulable parameters have shown a trend of positive relationship with high plasma viscosity in all β-1thalassemia TDT patients. The relative results suggested that our device would be an approach tool for early detection of hypercoagulable state in transfusion-dependent-β-thalassemia patients, which can help to prevent TEE and the critical consequent-complications.

Prevalence of osteoporosis &amp; osteopenia in transfusion-dependent thalassemia in Sulaimaniyah city, Iraq

Background and objectives: Although blood transfusion and iron chelation increase the lifespan of thalassemic patients, these patients face many complications, including osteoporosis and osteopenia. Thus, we aimed to determine prevalence rates of osteoporosis/osteopenia using Dual Energy X-Ray Absorptiometry in transfusion-dependent thalassemia patients and its relationship with chelation agents and body mass index. Methods: This retrospective study included 150 patients with transfusion-dependent thalassemia in the Thalassemia and Congenital Blood Disorders Center, Sulaimaniyah, Iraq, from December 2021 to July 2022. The participant’s information was collected from the hospital database, including sociodemographic characteristics, bone mineral density status, and the number of items used for chelation. A Dual Energy X-Ray Absorptiometry bone scan was used to check the bone mineral density. Results: The mean age of patients was 19.59±7.59, body mass index was 21.23±18.13, and most (53.3%) were females. Dual Energy X-Ray Absorptiometry results showed that 53.3% of the patients had osteopenia, 21.3% had osteoporosis, 36.7% had average bone mineral density, and 6.7% had low bone mineral density for age. In addition, there was a significant difference between the frequencies of bone density disorders in patients who used one chelating agent (46.4%) versus two chelating agents (85%) (P?0.001). Also, there was a significant difference between the incidence of bone density disorders with low and average body mass index (78%) in comparison with overweight and obese patients (8%) (P?0.001). Conclusions: There is a high prevalence of osteoporosis and osteopenia in transfusion-dependent thalassemia patients, which are more prone to trauma and bone fracture.

The relation between serum ferritin level and echocardiographic findings in transfusion dependent thalassemic patients in Slemani City, Kurdistan Region of Iraq.

Background and objectives: Thalassemia patients are at risk of iron overload. Those with transfusion-dependent thalassemia are more likely to experience cardiac problems because repeated blood transfusions cause iron accumulation in the cardiac myocyte. Thus, this study aims to determine the relationship between serum ferritin levels and echocardiographic findings in transfusion-dependent thalassemia patients. Methods: This retrospective analytical cross-sectional study was conducted on 131 patients with transfusion-dependent thalassemia between 1stDecember 2021 to 1stJuly 2022 at the Center for Thalassemia and Congenital Blood Disorder, Slemani, Iraq. The participant’s information, including sociodemographic characteristics such as age, gender, body weight, height, hemoglobin level, serum ferritin, type and duration of chelation therapy, and echocardiographic findings, were collected from the hospital database using a questionnaire. Then, the correlation between serum ferritin levels and echocardiographic results was determined. Results: The mean age of the patients was 21.24 ± 6.28 years, and most of them were males (55.7%), from the urban region (71%) and had an average body weight (68.7%). The mean serum ferritin level was 1876±1743.63 µg/L. The interpretation of the echocardiography results showed 38 patients (29%) had valvular heart diseases. Body mass index has a reverse linear relationship with ejection fraction(P=0.038) and a direct relationship with age(P&lt;0.001). However, no significant association was found between echocardiographic findings and serum ferritin(P=0.83). Conclusions: We found valvular heart diseases among the most common heart disorders in the patients. Suitable interventions and measures can significantly help manage the condition and reduce illness complications.

The frequency of clinical and subclinical hypothyroidism in transfusion dependent thalassemia patients in Slemani city /Iraq

Background and objective: Thyroid disorders caused by blood transfusion in thalassemia patients could affect human health and growth, this study was conducted to determine the frequency of clinical and subclinical hypothyroidism in blood transfusion-dependent thalassemia patients in the city of Slemani, Kurdistan Region, Iraq. Methods: The current study is a retrospective cross-sectional study (comparative analysis) conducted in Slemani center for thalassemia patients and congenital blood, between December 2021 and July 2022. Participants included l07 thalassemia patients with medical records the sampling method was a convenience method. The data was collected through the review of patients' files and blood tests, including( thyroid hormones, hemoglobin level, serum ferritin level), with a questionnaire that was completed through an interview with the patients. Results: The results of thyroid function tests have shown that 21/107 pateints (19.6%) have hypothyroidism, 6 patients have overt hypothyroidism, and 15 patients have subclinical showed that 23/107 patients and 4/107 patients had hight and low levels,respectively, and there was statistically a significant difference in the average Thyroid stimulating hormone and serum thyroxin levels in two groups of hypothyroid and euthyroid patients and mean ferritine serum level between these two groups was 2166.7±2174.8 and 2068.37±1919.97 respictively ,which was not a statistically significant difference . Conclusion: Considering the high prevalence of hypothyroidism in thalassemia patients, measuring Thyroid stimulating hormone and thyroxin can be very important and vital in the initial screenings,effective treatment and follow-up of patients.