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BMC Ophthalmology Jul 2016Beta-thalassemia is a severe genetic blood disorder caused by a mutation in the gene encoding for the beta chains of hemoglobin. Individuals with beta-thalassemia major... (Review)
Review
BACKGROUND
Beta-thalassemia is a severe genetic blood disorder caused by a mutation in the gene encoding for the beta chains of hemoglobin. Individuals with beta-thalassemia major require regular lifelong Red Blood Cell transfusions to survive. Ocular involvement is quite common and may have serious implications.
METHODS
Extensive review of observational studies on beta-thalassemia, to determine the prevalence and spectrum of ocular abnormalities, by clinical examination and multimodal imaging, and to investigate risk factors for their development.
RESULTS
Frequency of ocular involvement differs among various studies (41.3-85 %, three studies). Ocular findings in beta-thalassemia may correlate to the disease itself, iron overload or the chelating agents used. Beta-thalassemia ocular manifestations include ocular surface disease, as demonstrated by tear function parameters (two studies). Lens opacities are present in 9.3-44 % (five studies). Lenticular opacities and RPE degeneration correlated positively with use of desferrioxamine and deferriprone respectively (two studies). Ocular fundus abnormalities characteristic of pseudoxanthoma elasticum (PXE), including peau d'orange, angioid streaks, pattern dystrophy-like changes, and optic disc drusen are a consistent finding in seven studies. Patients with PXE-like fundus changes were older than patients without these fundus changes (two studies). Age (two studies) and splenectomy (one study) had the strongest association with presence of PXE-like fundus changes. Increased retinal vascular tortuosity independently of the PXE-like fundus changes was found in 11-17.9 % (three studies), which was associated with aspartate amino transferase, hemoglobin and ferritin levels (two studies). Fundus autofluorescence and electrophysiological testing (ERG and EOG) may indicate initial stages or more widespread injury than is suggested by fundus examination (two studies).
CONCLUSIONS
Beta-thalassemia may present with various signs, both structural and functional. Pseudoxanthoma elasticum like fundus changes are a frequent finding in patients with b-thalassemia. These changes increase with duration or severity of the disease. Retinal vascular tortuosity may be an additional disease manifestation related to the severity and duration of anemia and independent of the PXE-like syndrome. Patients with long-standing disease need regular ophthalmic checkups because they are at risk of developing PXE-like fundus changes and potentially of subsequent choroidal neovascularization.
Topics: Chelating Agents; Humans; Iron Overload; Observational Studies as Topic; Retinal Diseases; Vision Disorders; beta-Thalassemia
PubMed: 27390837
DOI: 10.1186/s12886-016-0285-2 -
Hematology/oncology and Stem Cell... Sep 2017Nontransfusion-dependent β-thalassemia (NTDβT) syndromes consist of β-thalassemia intermedia and moderate hemoglobin E/β thalassemias. They are characterized by... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE/BACKGROUND
Nontransfusion-dependent β-thalassemia (NTDβT) syndromes consist of β-thalassemia intermedia and moderate hemoglobin E/β thalassemias. They are characterized by varying degrees of chronic anemia and a wide spectrum of complications due to ineffective erythropoiesis and iron overload from chronic transfusions. Hydroxyurea (HU), an oral chemotherapeutic drug, is anticipated to decrease disease severity.
METHODS
We performed a meta-analysis to evaluate the clinical efficacy and safety of HU in NTDβT patients of any age. MEDLINE, EMBASE, Cochrane databases, and major conference proceedings for studies that assessed HU in NTDβT patients were searched. Qualities of eligible studies were assessed by National Institutes of Health tools.
RESULTS
Seventeen studies, collectively involving 709 patients, fulfilled the eligibility criteria. HU was associated with a significant decrease in transfusion need in severe NTDβT with complete and overall (≥50%) response rates of 42% and 79%, respectively. For mild NTDβT, HU was effective in raising hemoglobin by 1g/L in 64% of patients.
CONCLUSION
HU appears to be effective, well tolerated, and associated with mild and transient adverse events. NTDβT patients may benefit from a trial of HU, although large randomized clinical trials assessing its efficacy should be conducted to confirm the findings of this meta-analysis and to assess its long-term toxicity and response sustainability.
Topics: Adolescent; Adult; Blood Transfusion; Child; Child, Preschool; Humans; Hydroxyurea; Middle Aged; Young Adult; beta-Thalassemia
PubMed: 28408107
DOI: 10.1016/j.hemonc.2017.02.002 -
Journal of Community Genetics Dec 2023A large number of studies have reported that the prevalence of beta thalassemia carriers in India varies by ethnic groups. The objective of this study was to conduct a... (Review)
Review
A large number of studies have reported that the prevalence of beta thalassemia carriers in India varies by ethnic groups. The objective of this study was to conduct a systematic review of the published studies and conduct a meta-analysis to determine the prevalence of beta thalassaemia carriers in India. A PubMed database search using keywords "beta thalassaemia AND India" identified 1088 articles of which 69 articles were included in the review. Studies using diagnostic tests and methods recommended by the International Council for Standardization in Haematology were used for calculation of pooled prevalence. Pooled prevalence was calculated using a random effects model using Review Manager version 5.3. Studies had screened five categories of populations, that is, the general population; tribal groups, communities not belonging to tribal groups, persons with anemia, and persons referred with a suspicion of hemoglobinopathy. This heterogeneity contributed to a high pooled prevalence of beta thalassemia carriers of 8.23% (95% CI 7.36-9.10). Sub-group analysis however yielded 3.74% (95% CI 2.52-4.97) pooled prevalence of beta thalassemia carriers in the general population. It was 4.6% (95% CI 3.2-6.2) among tribal groups. Quality of prevalence studies was limited by methodological issues including non-random sampling methods, heterogeneity of population types screened, and lack of use of recommended diagnostic cut-offs. Prevalence of beta thalassemia carriers was similar in tribal populations and the general population, indicating the need to further investigate the prevalence of beta thalassemia carriers in tribal groups.
PubMed: 37861936
DOI: 10.1007/s12687-023-00683-7 -
Annals of Global Health Jun 2021Blood transfusion is a traditional treatment for β-thalassemia (β-thal) that improves the patients' anemia and lifespan, but it may lead to iron overload in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Blood transfusion is a traditional treatment for β-thalassemia (β-thal) that improves the patients' anemia and lifespan, but it may lead to iron overload in parenchymal tissue organs and endocrine glands that cause their dysfunctions as the iron regulatory system can't excrete excess iron from the bloodstream.
OBJECTIVE
To evaluate the prevalence of iron-related complications (short stature, growth retardation, and growth hormone deficiency) in β-thalassemia major (TM) patients.
METHODS
We performed an electronic search in PubMed, Scopus, and Web of Sciences to evaluate the prevalence of growth hormone impairment in β-thalassemia major (TM) patients worldwide. Qualities of eligible studies were assessed by the Joanna Briggs Institute checklist for the prevalence study. We used Comprehensive Meta-Analysis (Version 2) to calculate the event rate with 95% CIs, using a random-effects model for all analyses.
FINDINGS
Seventy-four studies were included from five continents between 1978 and 2019; 70.27% (Asia), 16.21% (Europe), 6.75% (Africa), 2.70% (America), 1.35% (Oceania), and 2.70% (Multicenter). The overall mean age of the participants was about 14 years. The pooled prevalence of short stature (ST) was 48.9% (95% CI 35.3-62.6) and in male was higher than female (61.9%, 95% CI 53.4-69.7 vs. 50.9%, CI 41.8-59.9). The pooled prevalence of growth retardation (GR) was 41.1% and in male was higher than in female (51.6%, 95% CI 17.8-84 vs. 33.1%, CI 9.4-70.2). The pooled prevalence of growth hormone deficiency (GHD) was 26.6% (95% CI 16-40.8).
CONCLUSION
Our study revealed that near half of thalassemia patients suffer from growth impairments. However, regular evaluation of serum ferritin levels, close monitoring in a proper institute, suitable and acceptable treatment methods besides regular chelation therapy could significantly reduce the patients' complications.
Topics: Adolescent; Blood Transfusion; Body Height; Dwarfism; Endocrine System Diseases; Female; Humans; Iron Overload; Male; beta-Thalassemia
PubMed: 34164261
DOI: 10.5334/aogh.3184 -
Cureus Nov 2022β-thalassemia is characterized by the faulty generation of hemoglobin resulting in an elevated α/β globin ratio; this led to several patients needing red blood cell... (Review)
Review
β-thalassemia is characterized by the faulty generation of hemoglobin resulting in an elevated α/β globin ratio; this led to several patients needing red blood cell (RBC) transfusions for the rest of their lives. Luspatercept is an erythroid maturation test for treating various types of anemia, including β-thalassemia. It inhibits the Smad2/3 cascade and treats β-thalassemia by downregulating the transforming growth factor-beta (TGF-β) pathway. Luspatercept was evaluated in randomized controlled trials (RCTs). However, there is still limited data. Therefore, the study aims to review the current literature to assess the efficacy of luspatercept in cure β-thalassemia and its safety. From 2015 to 2022, searches were undertaken in PubMed, Google Scholar, and Cochrane. Only RCTs published in English were eligible for inclusion. The Cochrane Collaboration tool for bias assessment was used to analyze the quality of the publications. Our search strategy revealed 94 publications, of which 12 full-text papers were read and five were chosen for this review.All five trials included 1161 participants. Of whom, 153 (13.18%) entered phase 2, and 1008 (86.82%) entered phase 3. Two articles included 153 participants, of whom 70 (45.75%) were transfusion-dependent beta-thalassemia (TD) and 83 (54.25%) were non-transfusion-dependent beta-thalassemia (NTD) of phase 2. Three articles included 1008 participants, of whom 672 (66.67%) were given luspatercept and 336 (33.33%) were given a placebo. All participants in RCTs were 18 years of age or older. In phase 2, 0.2 to 1.25 mg/kg of luspatercept was given, and in phase 3, 1.0 to 1.25 mg/kg of luspatercept was given once every three weeks. In beta-thalassemia patients, luspatercept was more effective than a placebo and well tolerated. The high dose has shown promising results in the erythroid response, measured by a drop in blood transfusions or an average rise in hemoglobin levels. Luspatercept might make patients less likely to need RBC transfusions, improve their clinical results, and improve their quality of life. Adverse events were hyperuricemia, arthralgia, dizziness, influenza hypertension, and bone pain, but they were manageable.
PubMed: 36540460
DOI: 10.7759/cureus.31570 -
Journal of Clinical Medicine Jul 2022Among the difficulties of living with β-thalassemia, patients frequently require blood transfusions and experience iron overload. As serum ferritin (SF) provides an...
Among the difficulties of living with β-thalassemia, patients frequently require blood transfusions and experience iron overload. As serum ferritin (SF) provides an indication of potential iron overload, we conducted a systematic literature review (SLR) to assess whether SF levels are associated with clinical and economic burden and patient-reported outcomes (PROs). The SLR was conducted on 23 April 2020 and followed by analysis of the literature. Dual-screening was performed at the title, abstract, and full-text levels using predefined inclusion and exclusion criteria. Ten studies identified by the SLR were eligible for inclusion in the analysis. Seven studies were conducted in Europe, and most were prospective or retrospective in design. The patient populations had a median age of 20.7-42.6 years, with a percentage of men of 38-80%. Sparse data were found on the correlation between SF levels and mortality, and hepatic, skeletal, and cardiac complications; however, in general, higher SF levels were associated with worsened outcomes. The bulk of the evidence reported on the significant association between higher SF levels and endocrine dysfunction in its many presentations, including a 14-fold increase in the risk of diabetes for patients with persistently elevated SF levels. No studies reporting data on PROs or economic burden were identified by the SLR. SF levels provide another option for prognostic assessment to predict a range of clinical outcomes in patients with β-thalassemia.
PubMed: 35956067
DOI: 10.3390/jcm11154448 -
Journal of Clinical Medicine Dec 2021In the last half century, the life expectancy of beta-thalassemia patients has strikingly increased mostly due to regular blood transfusions and chelation treatments.... (Review)
Review
In the last half century, the life expectancy of beta-thalassemia patients has strikingly increased mostly due to regular blood transfusions and chelation treatments. The improved survival, however, has allowed for the emergence of comorbidities, such as hearing loss, with a non-negligible impact on the patients' quality of life. This thorough review analyzes the acquired knowledge regarding hearing impairment in this hereditary hemoglobinopathy, aiming at defining its prevalence, features, course, and possible disease- or treatment-related pathogenic factors. Following PRISMA criteria, we retrieved 60 studies published between 1979 and 2021. Diagnostic tools and criteria, forms of hearing impairment, correlations with beta-thalassemia phenotypes, age and sex, chelation treatment and laboratory findings including iron overload, were carefully searched, analyzed and summarized. In spite of the relatively high number of studies in the last 40 years, our knowledge is rather limited, and large prospective studies with homogeneous diagnostic tools and criteria are required to define all the aforementioned issues. According to the literature, the overall prevalence rate of hearing impairment is 32.3%; age, sex, and laboratory findings do not seem to correlate with hearing deficits, while the weak relationship with clinical phenotype and chelation treatment seems to highlight the presence of further yet to be identified pathogenic factors.
PubMed: 35011846
DOI: 10.3390/jcm11010102 -
Iranian Journal of Medical Sciences Jan 2022Patients with beta-thalassemia (BT) are susceptible to psychological disorders such as depression. The present study was conducted to estimate the pooled prevalence of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with beta-thalassemia (BT) are susceptible to psychological disorders such as depression. The present study was conducted to estimate the pooled prevalence of depression among patients with BT in Iran.
METHODS
Domestic and international databases were searched for relevant articles published from 1991 until June 2019. We searched international databases such as Scopus, ISI, and Embase; Iranian databases such as SID, Magiran, and IranDoc; and Google Scholar and PubMed search engines. The MeSH keywords used were "depression", "mental health", "depressive disorder", "thalassemia", "beta-thalassemia major", "prevalence", "epidemiology", and "Iran". Relevant cross-sectional or cohort studies were included in the analysis. Cochran's test and the index were used to assess heterogeneity. The pooled prevalence and its 95% confidence interval (CI) were calculated using "metaprop" commands in Stata 14. In cases, where the statistic was greater than 50%, the random-effects model was used.
RESULTS
Eighteen eligible studies were included. The pooled prevalence of depression was 42% (95% CI: 33% to 52%), whereas the pooled prevalence of mild, moderate, severe, and extremely severe depression was 16% (95% CI: 11% to 22%), 13% (95% CI: 9% to 18%), 13% (95% CI: 9% to 17%), and 3% (95% CI: 0% to 8%), respectively. The pooled prevalence of depression in moderate- and high-quality studies was 45% (95% CI: 29% to 61%), and 39% (95% CI: 27% to 51%), respectively.
CONCLUSION
The high prevalence of depression highlights the urgent need for the establishment of interventions for the prevention, early detection, and treatment of depression among Iranian patients with BT.
Topics: Cross-Sectional Studies; Depression; Humans; Iran; Prevalence; beta-Thalassemia
PubMed: 35017773
DOI: 10.30476/ijms.2020.85941.1557 -
Frontiers in Medicine 2022β-thalassemia is a disease caused by genetic mutations including a nucleotide change, small insertions or deletions in the β-globin gene, or in rare cases, gross...
β-thalassemia is a disease caused by genetic mutations including a nucleotide change, small insertions or deletions in the β-globin gene, or in rare cases, gross deletions into the β-globin gene. These mutations affect globin-chain subunits within the hemoglobin tetramer what induces an imbalance in the α/β-globin chain ratio, with an excess of free α-globin chains that triggers the most important pathogenic events of the disease: ineffective erythropoiesis, chronic anemia/chronic hypoxia, compensatory hemopoietic expansion and iron overload. Based on advances in our knowledge of the pathophysiology of β-thalassemia, in recent years, emerging therapies and clinical trials are being conducted and are classified into three major categories based on the different approach features of the underlying pathophysiology: correction of the α/β-globin disregulation; improving iron overload and reverse ineffective erythropoiesis. However, pathways such as the dysregulation of transcriptional factors, activation of the inflammasome, or approach to mechanisms of bone mineral loss, remain unexplored for future therapeutic targets. In this review, we update the main pathophysiological pathways involved in β-thalassemia, focusing on the development of new therapies directed at new therapeutic targets.
PubMed: 35492364
DOI: 10.3389/fmed.2022.880752 -
Blood Advances Feb 2024Advancements in orally bioavailable iron chelators and MRI methods have improved life expectancy and reproductive potential in thalassemia major (TM) and thalassemia... (Meta-Analysis)
Meta-Analysis
Advancements in orally bioavailable iron chelators and MRI methods have improved life expectancy and reproductive potential in thalassemia major (TM) and thalassemia intermedia (TI). Pregnancy is associated with adverse maternal and neonatal outcomes, frequency of which has not been well delineated. This systematic review aims to provide risk estimates of maternal and fetal outcomes in TM and TI and explore pregnancy's impact on iron homeostasis. Fifteen studies (429 participants, 684 pregnancies) were included. Meta-analysis revealed a higher thrombosis risk in TI (3.7%) compared to TM (0.92%), unchanged from prepregnancy. Heart failure risks in the earlier years appeared similar (TM 1.6% vs TI 1.1%), and maternal mortality in TM was 3.7%, but with current management, these risks are rare. Gestational diabetes and pre-eclampsia occurred in 3.9% and 11.3% of TM pregnancies, respectively. Caesarean section rates were 83.9% in TM and 67% in TI. No significant difference in stillbirth, small for gestational age neonates, or preterm birth incidence between TM and TI was observed. In TM pregnancies, red cell requirements significantly increased (from 102 to 139 ml/kg/year, P = 0.001), and 70% of TI pregnancies required blood transfusions. As expected, increased transfusion alongside chelation cessation led to a significant increase in serum ferritin during pregnancy (TM by 1005 ng/mL; TI by 332 ng/mL, P < 0.0001). Deterioration in iron status was further reflected by an increase in liver iron concentration (from 4.6 to 11.9 mg/g dry weight, P < 0.0001), and myocardial T2-star (T2∗) magnetic resonance imaging decreased (from 36.2 ± 2.5 ms to 31.1 ms) during pregnancy. These findings emphasize the elevated maternal risk of iron-related cardiomyopathy during pregnancy and labor, stressing the importance of cardiac monitoring and postpartum chelation therapy resumption.
Topics: Humans; Infant, Newborn; Pregnancy; Female; beta-Thalassemia; Iron; Pregnancy Outcome; Cesarean Section; Premature Birth
PubMed: 38181780
DOI: 10.1182/bloodadvances.2023011636