Guideline for the management of conception and pregnancy in thalassaemia syndromes: A British Society for Haematology Guideline.

This comprehensive guideline, developed by a representative group of UK-based medical experts specialising in haemoglobinopathies, addresses the management of conception and pregnancy in patients with thalassaemia. A systematic search of PubMed and EMBASE using specific keywords, formed the basis of the literature review. Key terms included "thalassaemia," "pregnancy," "Cooley's anaemia," "Mediterranean anaemia," and others, covering aspects such as fertility, iron burden and ultrasonography. The guideline underwent rigorous review by prominent organisations, including the Endocrine Society, the Royal College of Obstetricians and Gynaecologists (RCOG), the United Kingdom Thalassaemia Society and the British Society of Haematology (BSH) guideline writing group. Additional feedback was solicited from a sounding board of UK haematologists, ensuring a thorough and collaborative approach. The objective of the guideline is to equip healthcare professionals with precise recommendations for managing conception and pregnancy in patients with thalassaemia.

Iron burden and endocrine complications in transfusion-dependent thalassemia patients In Sarawak, Malaysia: a retrospective study.

INTRODUCTION: Thalassaemia is one of the major health problems in Malaysia. With safe blood transfusion regime, the lifespan of patients with transfusion-dependent thalassaemia (TDT) has improved but at the cost of a higher risk of developing endocrine disorders. It is crucial for us to monitor the iron overload to prevent end organ damage. This study aims to evaluate the iron burden and prevalence of endocrinopathies in patients with TDT in Sarawak. MATERIALS AND METHODS: This retrospective cohort study was conducted between January 2020 to June 2020 in six government hospitals in Sarawak. A total of 89 patients with TDT, aged 10 years and above, were recruited. RESULTS: Out of the 89 patients, there were 54 males (60.7%) and 35 females (39.3%) with a median age of 21 years (range 10.0-65.0). Sixty-seven (75.3%) patients had betathalassaemia major and 15 (16.9%) patients had haemoglobin E beta-thalassaemia (HbE beta-thalassaemia), remaining seven patients had other genotypes. Thirty-one (34.8%) patients had mean serum ferritin 2500ng/ml and above, and 44 (66.6%) had liver iron concentration (LIC) ≥7mg/g. The prevalence of endocrine disorders in our cohort was 69.7%. The most common endocrinopathies were short stature (n=46, 51.7%), followed by hypogonadism (n=24, 26.9%), delayed puberty (n=23, 25.8%), hypothyroidism (n=10, 11.2%), diabetes mellitus (n=9, 10.1%), impaired glucose tolerance (n=6, 6.7%) and hypoparathyroidism (n=3, 3.3%). Endocrinopathies were significantly associated with age (p=0.01), age at initiating regular blood transfusion (p<0.01) and duration of regular blood transfusion (p<0.01). CONCLUSION: Our data shows that the development of endocrinopathies in TDT can be time dependent. Early detection of endocrine-related complications and prompt treatment with iron chelation therapy are important to improve morbidity and mortality. A multidisciplinary approach with good patient-doctor collaboration is the key to improving patient care in our settings.

Liver steatosis in patients with transfusion-dependent thalassaemia.

We evaluated the prevalence and the clinical associations of liver steatosis (LS) in patients with transfusion-dependent thalassaemia (TDT). We considered 301 TDT patients (177 females, median age = 40.61 years) enrolled in the Extension-Myocardial Iron Overload in Thalassaemia Network, and 25 healthy subjects. Magnetic resonance imaging was used to quantify iron overload and hepatic fat fraction (FF) by T2* technique and cardiac function by cine images. The glucose metabolism was assessed by the oral glucose tolerance test (OGTT). Hepatic FF was significantly higher in TDT patients than in healthy subjects (median value: 1.48% vs. 0.55%; p = 0.013). In TDT, hepatic FF was not associated with age, gender, serum ferritin levels or liver function parameters, but showed a weak inverse correlation with high-density lipoprotein cholesterol. The 36.4% of TDT patients showed LS (FF >3.7%). Active hepatitis C virus (HCV) infection, increased body mass index and hepatic iron were independent determinants of LS. A hepatic FF >3.53% predicted the presence of an abnormal OGTT. Hepatic FF was not correlated with cardiac iron, biventricular volumes or ejection fractions, but was correlated with left ventricular mass index. In TDT, LS is a frequent finding, associated with iron overload, increased weight and HCV, and conveying an increased risk for the alterations of glucose metabolism.

Proportion of Hypogonadism in Transfusion-Dependent Thalassemia Patients and Its Contributing Factors.

BACKGROUND: Beta thalassemia is a lifelong disease involving malformed red blood cells (RBC). One of the disease's complications is hypogonadism, in which adults tend to exhibit regression in sexual characteristics, experience sexual dysfunction, and therefore have a lower quality of life. Around 3-10% of the Indonesian population carries the beta-thalassemia gene. This study aimed to see the proportions of hypogonadism in transfusion-dependent thalassemia patients and its contributing factors. METHODS: This is a cross-sectional study involving 60 male patients admitted to three Indonesian general hospitals from July 2022 to July 2023. All patients were diagnosed with beta-thalassemia via chromatography hemoglobin analysis. We performed a single-time physical examination and laboratory examinations to determine FSH, LH, and free testosterone levels. The correlation between Hb and sexual hormone levels was analyzed using Spearman's rank correlation coefficient. ROC curve analysis was conducted afterward. All statistical analysis was done in SPSS version 29. RESULTS: 31 out of 60 thalassemia patients had hypogonadism. Pre-transfusion Hb count was found to be linearly correlated with FSH (r = 0.388, p = 0.049), LH (r = 0.338, p = 0.008), and free testosterone (r = 0.255, p = 0.049). ROC analysis indicated that pre-transfusion Hb was viable as a predictor for hypogonadism (AUC = 0.655, 65.5% sensitivity, 67.7% specificity). CONCLUSION: We confirmed the role of pre-transfusion Hb count as a potential predictor for hypogonadism due to the tissue hypoxia mechanism and transfusion-related iron overload in TDT patients. Decreased Hb is linearly correlated with FSH, LH, and testosterone levels. Decreased Hb also downregulates these factors.

Significant Inverse Correlation of Serum Levels of Osteoprotegerin (OPG) and Transferrin Saturation in Thalassemia Dependent Transfusion (TDT) Patients.

BACKGROUND: Osteoporosis is a major problem in transfusion-dependent thalassemia patients (TDT) patients. Osteoprotegerin (OPG) is one of several bone markers that are closely associated with osteoporosis in TDT patients. OPG is a glycoprotein that functions as a feedback receptor for the Receptor Activator of Nuclear Factor kappa B Ligand (RANKL), which is an alpha tumor necrosis factor receptor. One of the causes of decreased bone mass density is iron toxicity, which can be identified by showing elevated transferrin saturation. Bone mass dual X-ray absorptiometry (DEXA) is a gold standard for the diagnosis of osteoporosis, these procedures are not commonly available in Indonesia. This study was conducted to analyze the correlation between serum levels of OPG and transferrin saturation in TDT patients. METHODS: A correlational study with a cross-sectional approach analyzed data from TDT patients at Hemato-Oncology Medic Outpatient Clinic, Hasan Sadikin General Hospital, Bandung, Indonesia. Primary data were obtained through blood sampling and anthropometry measurement while secondary data were obtained from the patient's medical records. OPG and transferrin saturation levels were assessed using the ELISA method. Research data were analyzed using the rank Spearman correlation test. RESULTS: Data were collected from 51 research subjects (30 women dan 21 men). The median OPG level was 380 (170-1230) pg/mL and the median transferrin saturation level was 89.4 (66.7 - 96.2)%. Analysis of correlation showed a significant correlation between and transferrin saturation level with a coefficient value of r -0.539 and p-value <0.001. CONCLUSION: There was a significant inverse correlation between OPG with transferrin saturation in TDT patients.

Survival and causes of death in patients with alpha and beta-thalassemia in Northern Thailand.

BACKGROUND: Thalassemia is the most prevalent hereditary anaemia worldwide. Severe forms of thalassemia can lead to reduced life expectancy due to disease-related complications. OBJECTIVES: To investigate the survival of thalassemia patients across varying disease severity, causes of death and related clinical factors. PATIENTS AND METHODS: We conducted a retrospective review of thalassemia patients who received medical care at Chiang Mai University Hospital. The analysis focused on survival outcomes, and potential associations between clinical factors and patient survival. RESULTS: A total of 789 patients were included in our study cohort. Among them, 38.1% had Hb H disease, 35.4% had Hb E/beta-thalassemia and 26.5% had beta-thalassemia major. Half of the patients (50.1%) required regular transfusions. Sixty-five patients (8.2%) had deceased. The predominant causes of mortality were infection-related (36.9%) and cardiac complications (27.7%). Transfusion-dependent thalassemia (TDT) (adjusted HR 3.68, 95% CI 1.39-9.72, p = 0.008) and a mean serum ferritin level ≥3000 ng/mL (adjusted HR 4.18, 95% CI 2.20-7.92, p < 0.001) were independently associated with poorer survival. CONCLUSIONS: Our study highlights the primary contributors to mortality in patients with thalassemia as infection-related issues and cardiac complications. It also underscores the significant impact of TDT and elevated serum ferritin levels on the survival of thalassemia patients.

Application of the magnetic resonance 3D multiecho Dixon sequence for quantifying hepatic iron overload and steatosis in patients with thalassemia.

OBJECTIVE: To investigate the feasibility and diagnostic efficacy of a 3D multiecho Dixon (qDixon) research application for simultaneously quantifying the liver iron concentration (LIC) and steatosis in thalassemia patients. MATERIALS AND METHODS: This prospective study enrolled participants with thalassemia who underwent 3 T MRI of the liver for the evaluation of hepatic iron overload. The imaging protocol including qDixon and conventional T2* mapping based on 2D multiecho gradient echo (ME GRE) sequences respectively. Regions of interest (ROIs) were drawn in the liver on the qDixon maps to obtain R2* and proton density fat fraction (PDFF). The reference R2* value was measured and calculated on conventional T2* mapping using the CMRtools software. Correlation analysis, Linear regression analysis, and Bland-Altman analysis were performed. RESULTS: 84 patients were finally included in this study. The median R2*-ME-GRE was 366.97 (1/s), range [206.68 (1/s), 522.20 (1/s)]. 8 patients had normal hepatic iron deposition, 16 had Insignificant, 42 had mild, 18 had moderate. The median of R2*-qDixon was 376.88 (1/s) [219.33 (1/s), 491.75 (1/s)]. A strong correlation was found between the liver R2*-qDixon and the R2*-ME-GRE (r = 0.959, P < 0.001). The median value of PDFF was 1.76% (1.10%, 2.95%). 8 patients had mild fatty liver, and 1 had severe fatty liver. CONCLUSION: MR qDixon research sequence can rapidly and accurately quantify liver iron overload, that highly consistent with the measured via conventional GRE sequence, and it can also simultaneously detect hepatic steatosis, this has great potential for clinical evaluation of thalassemia patients.

Pancreatic iron in pediatric transfusion-dependent beta-thalassemia patients: A longitudinal MRI study.

BACKGROUND: In pediatric transfusion-dependent thalassemia (TDT) patients, we evaluated the prevalence, pattern, and clinical associations of pancreatic siderosis and the changes in pancreatic iron levels and their association with baseline and changes in total body iron balance. PROCEDURE: We considered 86 pediatric TDT patients consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Iron overload (IO) was quantified by R2* magnetic resonance imaging (MRI). RESULTS: Sixty-three (73%) patients had pancreatic IO (R2* > 38 Hz). Global pancreas R2* values were significantly correlated with mean serum ferritin levels, MRI liver iron concentration (LIC) values, and global heart R2* values. Global pancreas R2* values were significantly higher in patients with altered versus normal glucose metabolism. Thirty-one patients also performed the follow-up MRI at 18 ± 3 months. Higher pancreatic R2* values were detected at the follow-up, but the difference versus the baseline MRI was not significant. The 20% of patients with baseline pancreatic IO showed no pancreatic IO at the follow-up. The 46% of patients without baseline pancreatic IO developed pancreatic siderosis. The changes in global pancreas R2* between the two MRIs were not correlated with baseline serum ferritin levels, baseline, final, and changes in MRI LIC values, or baseline pancreatic iron levels. CONCLUSIONS: In children with TDT, pancreatic siderosis is a frequent finding associated with hepatic siderosis and represents a risk factor for myocardial siderosis and alterations of glucose metabolism. Iron removal from the pancreas is exceptionally challenging and independent from hepatic iron status.

Pulmonary Artery Hypertension in Transfusion-Dependent Thalassemia.

OBJECTIVE: Patients with transfusion-dependent thalassemia (TDT) are at risk of developing pulmonary artery hypertension (PAH) due to chronic hemolysis, iron overload, hypercoagulability and splenectomy. The objective of the study was to assess the prevalence and predictors of PAH in patients with TDT. METHODS: Patients aged 6-18 years with TDT were included. 2D-echocardiography was done to measure the pulmonary artery systolic pressure (PASP) and left ventricular ejection fraction (LVEF). T2* MRI was done to evaluate cardiac iron overload. N-terminal-pro brain natriuretic peptide (NT-pro BNP) level was also assessed. RESULTS: Out of 61 participants, PAH was noted in 19 (31.6%). Mean (SD) age of the patients with PAH and without PAH was 12.2 (3.8) and 9.6 (3.5) years, respectively (P = 0.016). Five of 19 patients with PAH (26.3%) had undergone splenectomy as against 5 of 41 patients without PAH (12.2%) (P = 0.17). Years since splenectomy was higher in the PAH group. Mean (SD) NT-Pro BNP levels were also higher in patients with PAH [63.80 (25.89) vs 41.97 (23.95), P = 0.01]. Significantly higher number of patients with PAH had cardiac T2* value of < 10 ms (P = 0.04). Age (OR 4.11; 95% CI 1.46-8.77), years since splenectomy (OR 3.24; 95% CI 1.30-7.86), NT-Pro BNP levels (OR 4.43; 95% CI 2.14-9.61) and cardiac T2* MRI (OR 2.46; 95% CI 2.18-6.90) values were predictors of PAH in patients with TDT. CONCLUSION: PAH was observed in 31.6% of patients, with older age and years since splenectomy being important risk factors. NT-Pro BNP can be used as screening test for detecting PAH.

Post-transfusion severe headache in a patient with thalassemia with superficial siderosis of the central nervous system: a case report and literature review.

BACKGROUND: Patients with severe thalassemia may experience adverse effects from transfusion such as fever, rash, and iron overload after long-term transfusion therapy. Severe headaches as a side effect of blood transfusion in patients with thalassemia are not commonly observed, especially when combined with superficial siderosis of the central nervous system, which is easily misdiagnosed and requires excessive examination and treatment. CASE PRESENTATION: A 31-year-old woman was admitted with severe headache and vomiting over 3 days following blood transfusion. She was diagnosed with intermediate α-thalassemia at 2 years of age and had a history of irregular blood transfusions. Physical examination revealed horizontal nystagmus with no other abnormal neurological signs. Magnetic resonance (MR) imaging, MR venography, MR arteriography, and cerebrospinal fluid analysis were normal. However, susceptibility-weighted imaging showed abnormal signals in the bilateral and fourth ventricles. Initial antibiotics, antivirals, decompression of intracranial pressure, iron chelation, and symptomatic treatments were administered; subsequently, small intermittent blood transfusions were cautiously administered for severe anemia. The patient's headache was gradually relieved, and she was discharged on day 9. At the 5-month follow-up, the patient's headache recurred following another transfusion. CONCLUSIONS: Severe post-transfusion headache in patients with thalassemia has not been fully recognized and is easily misdiagnosed, leading to excessive examination and treatment. Understanding the clinical features of transfusion-related headaches can help identify this complication, but the exact pathophysiological mechanism requires further research.

Health-related quality of life with standard and curative therapies in thalassemia: A narrative literature review.

Health-related quality of life (HRQOL) is a patient-reported outcome that assesses the impact of a disease or illness on different domains of a patient's life. Different general and disease-specific measures can be used to evaluate HRQOL. This article aimed to summarize the evidence for HRQOL among patients with transfusion-dependent (TDT) and non-transfusion-dependent thalassemia (NTDT). We included HRQOL data related to standard therapy with blood transfusions, iron chelation, and/or luspatercept in TDT and NTDT, as well as curative therapies for TDT, including hematopoietic stem cell transplant (HSCT) and gene therapy. Patients with thalassemia had worse HRQOL scores compared to the general population, and chronic pain was seen to increase in frequency and severity over time with age. NTDT patients reported worse physical health and functioning, mental health, general health, and vitality than TDT patients. However, TDT patients reported worse pain, change in health, and social support than NTDT. Most therapies improved overall HRQOL among thalassemia patients. Deferasirox, an oral iron chelator, was associated with more HRQOL benefits compared to deferoxamine, an intravenous iron chelator. Luspatercept showed clinically meaningful improvement in physical functioning among TDT and NTDT. Furthermore, HSCT and gene therapy were associated with better physical, emotional, and mental domains scores.

Modified Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease and Related Risk Factors in Patients With Thalassemia.

OBJECTIVE: This study aimed to explore the burden of magnetic resonance imaging (MRI) of cerebral small vessel disease (CSVD) in patients with thalassemia and related risk factors. METHODS: The clinical data and MRI of patients with thalassemia were retrospectively analyzed, and non-thalassemia controls with matched sex and age were selected. The modified MRI burden of CSVD included recent small subcortical infarct, presumed vasogenic white matter hyperintensity, presumed vasogenic lacunae, perivascular space (PVS), and brain atrophy. RESULTS: This study included 110 patients in each of the thalassemia and control groups. There was no significant difference in sex, age, and common cerebrovascular disease risk factors between the 2 groups. The patients with thalassemia had a higher red blood cell count and lower content of hemoglobin. The PVS and modified MRI burden scores in the thalassemia group were higher than in the control group. With the increase in age, patients with thalassemia have a more severe CSVD burden. CONCLUSION: Patients with thalassemia have a heavier modified MRI burden of CSVD than non-thalassemia patients, particularly PVS, and aging is an important risk factor for CSVD changes.

Luspatercept stimulates erythropoiesis, increases iron utilization, and redistributes body iron in transfusion-dependent thalassemia.

Luspatercept, a ligand-trapping fusion protein, binds select TGF-ß superfamily ligands implicated in thalassemic erythropoiesis, promoting late-stage erythroid maturation. Luspatercept reduced transfusion burden in the BELIEVE trial (NCT02604433) of 336 adults with transfusion-dependent thalassemia (TDT). Analysis of biomarkers in BELIEVE offers novel physiological and clinical insights into benefits offered by luspatercept. Transfusion iron loading rates decreased 20% by 1.4 g (~7 blood units; median iron loading rate difference: -0.05 ± 0.07 mg Fe/kg/day, p< .0001) and serum ferritin (s-ferritin) decreased 19.2% by 269.3 ± 963.7 µg/L (p < .0001), indicating reduced macrophage iron. However, liver iron content (LIC) did not decrease but showed statistically nonsignificant increases from 5.3 to 6.7 mg/g dw. Erythropoietin, growth differentiation factor 15, soluble transferrin receptor 1 (sTfR1), and reticulocytes rose by 93%, 59%, 66%, and 112%, respectively; accordingly, erythroferrone increased by 51% and hepcidin decreased by 53% (all p < .0001). Decreased transfusion with luspatercept in patients with TDT was associated with increased erythropoietic markers and decreasing hepcidin. Furthermore, s-ferritin reduction associated with increased erythroid iron incorporation (marked by sTfR1) allowed increased erythrocyte marrow output, consequently reducing transfusion needs and enhancing rerouting of hemolysis (heme) iron and non-transferrin-bound iron to the liver. LIC increased in patients with intact spleens, consistent with iron redistribution given the hepcidin reduction. Thus, erythropoietic and hepcidin changes with luspatercept in TDT lower transfusion dependency and may redistribute iron from macrophages to hepatocytes, necessitating the use of concomitant chelator cover for effective iron management.

Extramedullary hematopoiesis in ribs and severe pulmonary hypertension disease following intermediate beta-thalassemia: a case report.

BACKGROUND: Thalassemia is a type of congenital hemoglobinopathy that falls into the category of hemolytic anemias. Extramedullary hematopoiesis is a complication of this disease, which is a mechanism to compensate for chronic anemia in these patients, and imaging is the best diagnostic method. CASE REPORT: In this report, a 36-year-old Caucasian female patient with intermediate beta thalassemia is presented who, at the time of referral, complained of exacerbated shortness of breath. Imaging showed diffuse expansion masses with soft tissue components in the ribs of both hemithoraxes, leading to the diagnosis of extramedullary hematopoiesis. CONCLUSION: Extramedullary hematopoiesis in the ribs is an uncommon finding in patients with thalassemia and is a sign of the severity of the disease and a poor prognostic factor that might be preventable if blood transfusion begins at younger ages.

CHMMOTv1 - cardiac and hepatic multi-echo (T2*) MRI images and clinical dataset for Iron overload on thalassemia patients.

INTRODUCTION: Regarding deep learning networks in medical sciences for improving diagnosis and treatment purposes and the existence of minimal resources for them, we decided to provide a set of magnetic resonance images of the cardiac and hepatic organs. DATABASE DESCRIPTION: The dataset included 124 patients (67 women and 57 men) with thalassemia (THM), the age range of (5-52) years. Patients were divided into two groups: with follow-up (1-5 times) at time intervals of about (5-6) months and without follow-up. T2* and, R2* values, the results of the Cardiac and Hepatic overload report (normal, mild, moderate, severe), and laboratory tests including Ferritin, Bilirubin (D, and T), AST, ALT, and ALP levels were provided as an Excel file. Also, the details of the patients' Echocardiogram data have been made available. This dataset CHMMOTv1) has been published in Mendeley Dataverse and also is accessible through the web at: http://databiox.com .

Sickle cell disease and pregnancy.

Pregnancy is a particularly risky period in the life of patients with sickle cell disease (SCD). Physiological changes during pregnancy increase the risk of vaso-occlusive crises (VOC), acute chest syndrome, venous thromboembolic events, and infections. This concerns haemoglobin (Hb) S/C and S/ß+-thalassaemia patients as much than S/S or S/ß0-thalassaemia patients. SCD also increases the risk of obstetrical complications, such as preeclampsia, in utero foetal death, preterm delivery mostly induced, and intrauterine growth restriction. Thus, pregnancy should be planned and closely monitored by a multidisciplinary team involving obstetricians and sickle cell disease specialists. Before pregnancy, the parents should also be informed about the risk of transmission of this autosomal recessive disease, and the father should therefore be prescribed haemoglobin electrophoresis. Treatments have to be revised when planning pregnancy: hydroxyurea (HU) should be stopped as soon as pregnancy is suspected or confirmed. Preventive blood transfusion is not systematic, but is recommended in the case of a pre-existing transfusion program prior to pregnancy, severe pre-existing organ damage, severe obstetric history, and severe or repeated crises during follow-up, especially in patients taking HU before. Despite the risks of prematurity, systematic administration of corticosteroids for foetal lung maturation is not recommended due to the risk of maternal vaso-occlusive event. Although more frequent, due to obstetrical and maternal complications, caesarean section is not systematic, in the absence of maternal contraindications. It is advisable not to exceed the term of 39 weeks of amenorrhoea. Post-partum follow-up is recommended, particularly because of the risk of thromboembolism.

Prevalence, Severity, and Determinants of Pain in Thalassemia.

As the life expectancy in thalassemia is improving, pain is being recognized as an emerging problem. To document the pain prevalence and severity in patients with transfusion-dependent thalassemia all transfusion-dependent thalassemia patients >10 years of age (n = 165) attending the Thalassemia Day Care Center were assessed for pain prevalence, severity, and its effect on various life activities using the Brief Pain Inventory. Their medical records were reviewed for the presence of various co-morbidities. Pain was reported by 62.4% of participants with 35.2% and 59.4% of participants, reporting pain in the past 1 and 4 weeks respectively. A significantly higher pain prevalence was reported in females (p = .037), patients residing in urban areas (p = .038), and employed participants (p = .038). The commonest sites of pain were the lower back and calves. General activity (p = .02) and enjoyment of life (p = .02) were significantly affected due to pain in patients between 21 and 30 years of age. Female participants reported interference of pain with mood (p = .03). A significant correlation of pain prevalence was found with higher average serum ferritin (p = .015), moderate to severe liver iron concentration (p = .04), and lower levels of 25 hydroxyvitamin D levels (p = .03). Pain is an emerging cause of morbidity in thalassemia. The study found a significant association of pain with modifiable factors such as serum ferritin, LIC, and 25 (OH) vitamin D levels.

Cardiac complications in thalassemia throughout the lifespan: Victories and challenges.

Thalassemias are among the most common hereditary diseases in the world because heterozygosity offers protection against malarial infection. Affected individuals have variable expression of alpha or beta chains that lead to their unbalanced utilization during hemoglobin formation, oxidative stress, and apoptosis of red cell precursors prior to maturation. Some individuals produce sufficient hemoglobin to survive but suffer the vascular stress imposed by chronic anemia and ineffective erythropoiesis. In other patients, mature red cell formation is insufficient, and chronic transfusions are required-suppressing anemia and ineffective erythropoiesis but at the expense of iron overload. The cardiovascular consequences of thalassemia have changed dramatically over the previous five decades because of evolving treatment practices. This review summarizes this evolution, focusing on complications and management pertinent to modern patient cohorts.

Perturbations in lipid metabolism and gut microbiota composition precede cardiac dysfunction in a mouse model of thalassemia.

Cardiomyopathy is a major complication of thalassemia, yet the precise underlying molecular mechanisms remain unclear. We examined whether altered lipid metabolism is an early driving factor in the development of cardiomyopathy using the Th3/+ mouse model of thalassemia. At age 20 weeks, male and female Th3/+ mice manifested anemia and iron overload; however, only males displayed metabolic defects and altered cardiac function. Untargeted lipidomics indicated that the circulating levels of 35 lipid species were significantly altered in Th3/+ mice compared to wild-type controls: triglycerides (TGs) with saturated fatty acids (FAs; TG42:0 and TG44:0) were elevated, while TGs with unsaturated FAs (TG(18:2_20:5_18:2 and TG54:8)) were reduced. Similarly, phosphatidylcholines (PCs) with long chain FAs (palmitic (16:0) or oleic (18:1)) were increased, while PCs with polyunsaturated FAs decreased. Circulating PC(16:0_14:0), GlcCer(d18:1/24:0) correlated significantly with iron overload and cardiac hypertrophy. 16S rRNA gene profiling revealed alterations in the intestinal microbiota of Th3/+ mice. Differentially abundant bacterial genera correlated with PC(39:6), PC(18:1_22:6), GlcCer(d18:1/24:1) and CE(14:0). These results provide new knowledge on perturbations in lipid metabolism and the gut microbiota of Th3/+ mice and identify specific factors which may represent early biomarkers or therapeutic targets to prevent development of cardiomyopathy in ß-thalassemia.

Thalassemia and malignancies: Updates from the literature.

Thalassemia management has undergone significant development with the advancement in iron chelation therapy, which has led to a prolonged life expectancy. This has been accompanied by the emergence of several new morbidities and chronic diseases, including cancer. Over the years, multiple cases of solid and hematologic malignancies in thalassemia patients have been reported in the literature, with no clear mechanism for the development of cancer in these patients despite a number of potential mechanisms. However, the results of many studies have been contradictory regarding the risk of development of malignancies in thalassemia. The present review aims to discuss the available data on cancer and thalassemia in the literature, with the latest updates regarding possible malignancy development mechanisms, risks, and the most commonly reported types.