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1.
J Cardiovasc Echogr ; 32(1): 17-22, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35669139

RESUMO

Background: Iron overload and cardiac dysfunctions are common complications in patients with thalassemia major (TM). Different imaging methods can be used to detect ventricular dysfunction in these patients. In this study, we aim to understand the value of tissue Doppler imaging (TDI) in the detection of myocardial dysfunction in patients with TM who have been diagnosed with iron overload using cardiovascular magnetic resonance CMRT2*. Methods: In this cross-sectional study, fifty patients with TM diagnosed with iron overload who had no clinical signs and symptoms of cardiac dysfunction were chosen as a case group. The control group included fifty sex- and age-matched healthy participants without a history of cardiac and hematological diseases. TDI, pulsed wave Doppler (PWD), and standard echocardiography were performed to study the left ventricular function, and cardiac iron overload assessed by CMRT2*. Then, the patients with TM were divided into two subgroups and compared with each other. Group 1a includes individuals with T2* value <20 ms and group 1b T2* value >20 ms. Results: There was no significant difference between the standard echocardiography results and PWD parameters of the case and control groups; however, CMRT2* findings and TDI parameters were different between the case and control groups. CMRT2* findings also were not correlated with PWD parameters. In group 1a, CMRT2* findings were negatively correlated with age, E', A', early deceleration time, and isovolumetric relaxation time and positively correlated with E/E' ratio. Finally, PWD and TDI parameters were significantly different between the two subgroups. Conclusion: TDI can detect ventricular systolic and diastolic dysfunctions in earlier stages among patients with iron overload. It seems that TDI could detect abnormalities more accurately, and it is better to consider subclinical cardiac dysfunction in patients with even CMRT2* value of more than 20 ms and reevaluate them in future.

2.
Biology (Basel) ; 11(6)2022 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-35741383

RESUMO

Beta (ß)-thalassemia is a group of human inherited abnormalities caused by various molecular defects, which involves a decrease or cessation in the balanced synthesis of the ß-globin chains in hemoglobin structure. Traditional treatment for ß-thalassemia major is allogeneic bone marrow transplantation (BMT) from a completely matched donor. The limited number of human leukocyte antigen (HLA)-matched donors, long-term use of immunosuppressive regimen and higher risk of immunological complications have limited the application of this therapeutic approach. Furthermore, despite improvements in transfusion practices and chelation treatment, many lingering challenges have encouraged researchers to develop newer therapeutic strategies such as nanomedicine and gene editing. One of the most powerful arms of genetic manipulation is gene editing tools, including transcription activator-like effector nucleases, zinc-finger nucleases, and clustered regularly interspaced short palindromic repeat-Cas-associated nucleases. These tools have concentrated on γ- or ß-globin addition, regulating the transcription factors involved in expression of endogenous γ-globin such as KLF1, silencing of γ-globin inhibitors including BCL11A, SOX6, and LRF/ZBTB7A, and gene repair strategies. In this review article, we present a systematic overview of the appliances of gene editing tools for ß-thalassemia treatment and paving the way for patients' therapy.

3.
Int J Mol Sci ; 23(11)2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35682629

RESUMO

Prime editing was used to insert and correct various pathogenic mutations except for beta-thalassemia variants, which disrupt functional beta-globin and prevent hemoglobin assembly in erythrocytes. This study investigated the effect of gene correction using prime editor version 3 (PE3) in a mouse model with the human beta-thalassemia IVS-II-654 mutation (C > T). The T conversion generates a 5' donor site at intron 2 of the beta-globin gene resulting in aberrant splicing of pre-mRNA, which affects beta-globin expression. We microinjected PE3 components (pegRNA, nick sgRNA, and PE2 mRNA) into the zygotes from IVS-II-654 mice to generate mutation-edited mice. Genome sequencing of the IVS-II-654 site showed that PE3 installed the correction (T > C), with an editing efficiency of 14.29%. Reverse transcription-PCR analysis showed that the PE3-induced conversion restored normal splicing of beta-globin mRNA. Subsequent comprehensive phenotypic analysis of thalassemia symptoms, including anemic hematological parameters, anisocytosis, splenomegaly, cardiac hypertrophy, extramedullary hematopoiesis, and iron overload, showed that the corrected IVS-II-654 mice had a normal phenotype identical to the wild type mice. Off-target analysis of pegRNA and nick sgRNA additionally showed the genomic safety of PE3. These results suggest that correction of beta-thalassemia mutation by PE3 may be a straightforward therapeutic strategy for this disease.

4.
Cureus ; 14(4): e23770, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35509765

RESUMO

Beta-thalassemia represents a range of hemoglobinopathies that are a consequence of an impairment in the synthesis of beta-globin chains. They result in different degrees of hemolysis and ineffective erythropoiesis, depending on the underlying mutations. They can lead to severe complications mainly resulting from anemia. However, there is no bleeding tendency in this disorder, and it is uncommon to see hematoma formation in affected patients. To our knowledge, subperiosteal hematomas have been rarely described in the context of beta-thalassemia. Herein, we report a unique case of a 19-year-old boy who was diagnosed with transfusion-dependent beta-thalassemia and secondary hemochromatosis and developed atraumatic subperiosteal hematomas along the humerus.

5.
Pak J Med Sci ; 38(4Part-II): 878-882, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35634613

RESUMO

Objective: To observe the role of Mentzer index for differentiating iron deficiency anemia (IDA) and beta thalassemia trait (ß TT) in pregnant women. Methods: This cross-sectional study was conducted in Gynaecology & Obstetrics Department of Nishtar Medical University from October 2020 to March 2021. Non-consecutive sampling was applied. A total of 100 antenatal ladies with hemoglobin <11 gm/dl were included. Their complete blood counts were checked and Mentzer Index was calculated. Mentzer Index <13 points to diagnosis of ß TT and >13 indicates IDA. The diagnoses were confirmed by serum iron studies and Hb electrophoresis. The sensitivity and specificity of Mentzer Index for both causes of microcytic hypochromic anemia was calculated. Results: Out of total 100 patients with microcytic hypochromic anemia, 87 had Mentzer Index >13 and IDA was confirmed in 86 out of 87 cases. Thirteen cases had Mentzer Index <13 and ß TT was confirmed in eight of them. Thus, Mentzer Index has a sensitivity and specificity of 91% & 83% for IDA and 83% & 91% for ß TT. Conclusion: In this study, it was found that Mentzer Index can be used as a discriminatory test to differentiate between iron deficiency anemia and beta thalassemia trait. The high risk group can then be subjected to definitive diagnostic tests. This can result in better patient compliance and cost effectiveness.

6.
J Fluoresc ; 2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35622216

RESUMO

A wide variety of medical, biomedical, and industrial applications has been reported for quinoxalines derivatives. In this work, a novel quinoxaline derivative was designed and synthesized. Naked-eye and quantitative detection of Fe3+ among several cations were evaluated using UV-Vis spectroscopy. New chemosensor, 2,3-bis(6-bromopyridine-2-yl)-6-chloroquinoxaline named BPQ, showed a selective interaction for iron ion over other tested cations by changing color. Iron overloaded mice were prepared as a thalassemia model and then the effects of iron-chelating activities of BPQ were experienced. The job's plot methods determined the stoichiometric ratio of ligand to Fe3+ (1:1). The iron content in serum was evaluated by atomic absorption spectroscopy (AAS). Results showed significant differences (two-fold decrease in total iron and Fe3+) between the iron overloaded and BPQ (dose of 20 mgkg-1). The BPQ was identified as a ligand, which can be applied as a new chelator for decreasing the excess iron of blood.

7.
Int J Mol Sci ; 23(9)2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35563395

RESUMO

Recently developed Prime Editor 3 (PE3) has been implemented to induce genome editing in various cell types but has not been proven in human hematopoietic stem and progenitor cells. Using PE3, we successfully installed the beta-thalassemia (beta-thal) mutations in the HBB gene in the erythroid progenitor cell line HUDEP-2. We inserted the mCherry reporter gene cassette into editing plasmids, each including the prime editing guide RNA (pegRNA) and nick sgRNA. The plasmids were electroporated into HUDEP-2 cells, and the PE3 modified cells were identified by mCherry expression and collected using fluorescence-activated cell sorting (FACS). Sanger sequencing of the positive cells confirmed that PE3 induced precise beta-thal mutations with editing ratios from 4.55 to 100%. Furthermore, an off-target analysis showed no unintentional edits occurred in the cells. The editing ratios and parameters of pegRNA and nick sgRNA were also analyzed and summarized and will contribute to enhanced PE3 design in future studies. The characterization of the HUDEP-2 beta-thal cells showed typical thalassemia phenotypes, involving ineffective erythropoiesis, abnormal erythroid differentiation, high apoptosis rate, defective alpha-globin colocalization, cell viability deterioration, and ROS resisting deficiency. These HUDEP-2 beta-thal cells could provide ideal models for future beta-thal gene therapy studies.


Assuntos
Células Precursoras Eritroides , Edição de Genes , Hemoglobinas , Talassemia beta , Células Precursoras Eritroides/metabolismo , Edição de Genes/métodos , Hemoglobinas/genética , Hemoglobinas/uso terapêutico , Humanos , Mutação , alfa-Globinas/genética , Globinas beta/genética , Talassemia beta/genética , Talassemia beta/terapia
8.
Clin Case Rep ; 10(4): e05705, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35414927

RESUMO

Beta-thalassemia is congenital red blood cell disorder. Gallstones is a recognized complication due to recurrent hemolysis. Acute cholangitis is a rare complication might occur in patient with beta-thalassemia. We report a case of acute cholangitis in patient with beta-thalassemia with Gilbert syndrome. We present a case of a young female of Arabic descent with acute abdomen. Workup revealed acute cholangitis with gallstones in the common bile duct. The ERCP was used to extract the stones than cholecystectomy.

9.
Front Med (Lausanne) ; 9: 866396, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402459

RESUMO

Objectives: To verify with hematimetric data that the diagnosis and clinical grade of ß-TI can be established when a triplication of alpha genes (αααanti 3.7) and heterozygous ß-thalassemia coexist. Materials and Methods: Retrospective study in which 73 patients of Caucasian origin participated, who simultaneously showed a triplication or quadruplication of genes α and ß-thalassemia.Screening for the most frequent α-thalassemia mutations as well as gene triplication (αααanti 3.7) was carried out by multiplex PCR followed by reverse hybridization with a commercial Alpha-Globin StripAssay kit and confirmed by MLPA (Multiplex ligation-dependent probe amplification). The molecular diagnosis of ß-thalassemia was carried out by automatic sequencing according to the Sanger method. Results: The genotypes have been classified into three groups according to the number of α globin genes and the severity of the alteration in the ß globin gene. All had a mutation in the HBB gene (ß0-thalassemia, ß+-thalassemia severe, and ß+-thalassemia mild). Group I patients who have coherent 6 α genes and groups II and III with 5 α globin genes. In group III, the patients were carriers of mutations affecting the ß and δ globin genes. The most significant hematological parameters were hemoglobin levels, MCV, RDW, and the percentage of Hb F. Conclusions: In group I, regardless of the distribution of the 6 α globin genes, homozygous triplication (ααα/ααα) or heterozygous quadruplication (αααα/αα), the association with heterozygous ß-thalassemia results in severe to moderate anemia that may or may not require transfusion therapy, is the severity of the HBB gene mutation that would determine the clinical variation. Group II patients phenotypically behaved like mild thalassemia intermedia, except for one case that presented thalassemic trait because it also presented an associated α-thalassemia (ααα/-α3.7). Finally, group III patients behaved as a thalassemic trait since all were carriers of mutations that increase the overexpression of γ genes.

10.
J Clin Med ; 11(7)2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35407657

RESUMO

Pregnancy in women with thalassemia minor is considered safe. However, a higher incidence of maternal and neonatal complications in women with the disorder has been reported in the literature. This study aimed to determine whether there is an increased risk of gestational diabetes mellitus (GDM) in pregnant women with beta-thalassemia minor. We conducted a retrospective matched case-control study of 230 pregnant women who delivered at the Department of Obstetrics and Feto-Maternal Medicine at the Medical University of Vienna between the years 2008 and 2020, whereof 115 women had beta-thalassemia minor. We found no significant difference in the occurrence of GDM between the case group and control group of age and BMI-matched healthy women. However, we observed a significantly lower hemoglobin (Hb) and hematocrit (Ht) level during the first, the second, and the third trimesters of pregnancy, and postpartum (all: p < 0.001) among women with beta-thalassemia minor compared to the healthy controls. Neonates of women with beta-thalassemia were more likely to experience post-natal jaundice and excessive weight loss (p < 0.001). We conclude that GDM is not more likely to occur in pregnant women with beta-thalassemia minor. However, clinicians should be made aware of the risk of adverse maternal and neonatal outcomes. Furthermore, women with beta-thalassemia minor should undergo regular laboratory screening and multidisciplinary pregnancy care.

11.
Cureus ; 14(3): e23293, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35449671

RESUMO

Sickle cell disease variants can commonly present as life-threatening complications, like sequestration crisis, hypersplenism, or stroke. However, clinicians should also look for milder findings like asymptomatic chronic anemia mimicking iron deficiency as a milder, more insidious clue to an underlying sickle cell variant. Early investigations of these milder symptoms can potentially reduce the risk of more severe complications such as vaso occlusive crisis. In this report, we present a 75-year-old African-American female, who was referred to the hematology clinic for chronic anemia without any history of vaso occlusive crisis and was eventually diagnosed with sickle cell beta plus thalassemia as per hemoglobin electrophoresis. Here, we review the challenges in diagnosing rarer types of sickle cell disease and the importance of educating patients about the diagnosis. This rare type demands clinicians' awareness to identify the disease early and to understand the etiology of the complications, if any, that occur.

12.
Ann Hematol ; 101(7): 1473-1483, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35460387

RESUMO

The presence of atrial cardiomyopathy in ß-thalassemia major (ß-TM) patients complicates their clinical condition. The diagnosis is challenging even with cardiac magnetic resonance (CMR) imaging. Novel echocardiographic techniques are applied to increase the diagnostic yield. Fifty-six ß-TM patients and thirty age and sex-matched controls were included in the present cross-sectional study. Heart rate, PR duration, and P axis were measured by electrocardiography, left ventricular ejection fraction (LVEF) and end-diastolic diameter (LVEDD), ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e'), left atrial volume index (LAVI), left atrial strain at reservoir (LASr), conduit (LAScd) and contraction (LASct) phases respectively, left ventricular global longitudinal strain (GLS) by echocardiography, and T2* calculation in patient group by CMR. PR duration, LVEF, LAVI, E/e', GLS, and left atrial deformation parameters differed between patients and controls (p <0.05). In patient group, left atrial strain was correlated with PR duration, LAVI, E/e', GLS, and T2* (p <0.05). T2* was correlated only with left atrial deformation indices (p <0.05). Patients with a history of atrial fibrillation were older, had lower heart rate, prolonged PR, increased E/e' and LAVI, and impaired left atrial strain (p <0.05). LASct differed relative to the presence of atrial fibrillation and myocardial iron overload. Atrial strain could be of clinical use in the early detection of atrial cardiomyopathy. An impaired LASct could identify ß-TM patients with undetected episodes of atrial fibrillation. Finally, left atrial strain may be helpful in myocardial iron load estimation.


Assuntos
Fibrilação Atrial , Cardiomiopatias , Disfunção Ventricular Esquerda , Talassemia beta , Fibrilação Atrial/complicações , Fibrilação Atrial/etiologia , Cardiomiopatias/etiologia , Estudos Transversais , Átrios do Coração/diagnóstico por imagem , Humanos , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda/fisiologia , Talassemia beta/complicações , Talassemia beta/diagnóstico por imagem
13.
Calcif Tissue Int ; 111(1): 56-65, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35243531

RESUMO

Osteoporosis represents a relevant cause of morbidity in adult Thalassemia Major (TM) population. Antiresorptive drugs such as bisphosphonates were demonstrated effective in preventing bone loss. Teriparatide (TP) is an anabolic agent approved for osteoporosis management in the general population, but its use has been very limited in TM patients so far. We evaluated TP efficacy and safety in TM-associated osteoporosis in real-life clinical practice. Retrospective evaluation of 11 TM patients (6 males, 5 females; mean age = 45 ± 4.38 years) with severe osteoporosis and multiple fractures under TP treatment. Mean TP treatment duration was 19 ± 7 months. TP withdrawal was due to poor compliance and side effects (fever and osteo-muscular pain) in two and three patients, respectively. After 12 and 24 months, BMD significantly increased at lumbar (+ 19% and 22%) and femoral sites (+ 13% and 13%). Osteocalcin and cross-laps levels increased after 12 and 24 months (+ 225 and + 54.2%; + 159 and 141%, respectively). No new fractures were detected during TP treatment. Baseline VAS score values (3 ± 3) did not significantly change after 12 and 24 months (3 ± 3 and 2 ± 3, respectively). Five out of eleven patients developed side effects. TP might be an effective treatment for TM-associated osteoporosis since it improves BMD, especially at the lumbar spine, and prevents fragility fractures. TM patients may have a higher frequency of side effects, especially muscle and bone pain under TP treatment, as compared to no TM population. Further studies are needed.

14.
J Endocrinol Invest ; 45(7): 1439-1445, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35305249

RESUMO

PURPOSE: GH deficit (GHD) could represent an endocrine issue in ß-Thalassemia Major (ßTM) patients. GH/IGF-1 axis has not been extensively explored in ßTM adults, so far. We aim to assess GHD and IGF-1 deficiency prevalence in ßTM adult population, focusing on the relationship with liver disease. METHODS: Cross-sectional multi-centre study conducted on 81 adult ßTM patients (44 males, mean age 41 ± 8 years) on transfusion and chelation therapy. GHD was investigated by GHRH + arginine test. IGF-1 levels, routine biochemical exams, Fibroscan, Hepatic Magnetic Resonance Imaging (MRI) and pituitary MRI were collected. RESULTS: Eighteen patients were affected by GHD and 63 were not (nGHD) according to GHRH + arginine test, while basal GH levels did not differ. GHD was associated with a higher BMI and a worse lipid profile (p < 0.05). No significant differences were observed regarding liver function between the two groups. Pituitary MRI scan was normal except for one case of empty sella. The 94.4% and 93.6% of GHD and nGHD, respectively, presented lower IGF-1 levels than the reference range, and mean IGF-1 SDS was significantly lower in GHD patients. CONCLUSION: GHD is frequent in adult ßTM patients and is associated with higher BMI and worse lipid profile. nGHD patients present lower IGF-1 levels as well. There was no relationship between IGF-1 levels and liver disease. Further, multicentric studies with larger cohorts and standardized diagnostic protocols are needed.


Assuntos
Hormônio do Crescimento Humano , Talassemia beta , Adulto , Arginina , Estudos Transversais , Humanos , Fator de Crescimento Insulin-Like I , Lipídeos , Masculino , Pessoa de Meia-Idade , Talassemia beta/complicações , Talassemia beta/epidemiologia
15.
Hematol Rep ; 14(1): 2-12, 2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-35323173

RESUMO

BACKGROUND: People living with transfusion dependent thalassemia have a high risk of becoming infected with COVID-19. This can be caused by both internal factors, namely the formation of alloantibodies and autoimmune disorder, and external factors such as routine visits for blood transfusions. Chronic complications of thalassemia also render them more vulnerable to infectious diseases, including COVID-19. However, anecdotal data shows that thalassemia patients experience less incidence of COVID-19 compared to the general population. PURPOSE: This study aims to find the correlation between COVID-19 in thalassemia-dependent transfusion patients in Indonesia and Southeast Asia. PATIENTS AND METHODS: This study used a cross-sectional design. The study was conducted at the Division of Hematology and Medical Oncology of the Cipto Mangunkusumo Hospital in Jakarta from May 2020-August 2021. The total sampling method was used involving all thalassemia major patients who had been infected with COVID-19 (obtained directly from medical record and through the thalassemia patients-parents foundation). RESULTS: From 10,397 patients with thalassemia, 67 (0.64%) people were infected by COVID-19 and 2 (2.9%) were deceased. Meanwhile, the incidence of COVID-19 in the general population of Indonesia was 0.87% (more than in the thalassemia population). This means that thalassemia might provide additional protection against COVID-19 due to several mechanisms. This phenomenon has also been seen in other countries with a high prevalence of thalassemia, wherein there are less COVID-19 cases despite the pandemic. On the contrary, countries with low rates of thalassemia had experienced deadly surges of the pandemic. CONCLUSION: Indonesia and other countries with a high prevalence of thalassemia have lower COVID-19 incidence than countries with low prevalence of thalassemia. Thalassemia might provide additional protection against COVID-19. Well-designed studies are needed to provide better evidence on the protective effect of thalassemia on COVID-19.

16.
Diagnostics (Basel) ; 12(3)2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35328209

RESUMO

Cunninghamella spp. is a group of fungi belonging to the Mucorales order. Cases of fungal endocarditis are sporadic, but more frequent in immunocompromised patients. COVID-19 (SARS-CoV-2 Infection Disease 2019) infections, prematurity, deferoxamine treatment, iron overload, neutropenia, diabetes, and malignant hemopathies proved to be risk factors for mucormycosis. We present the case of a 7-year-old boy who was treated every three weeks with blood transfusion for major beta-thalassemia, receiving deferoxamine for secondary hemochromatosis. After two weeks with nonspecific respiratory and digestive symptoms, he was admitted for fever, followed by lower limb ischemia and neurological signs. Echocardiography revealed massive endocarditis affecting the mitral and tricuspid valves with embolization phenomena in the brain, lungs, kidney, spleen, and lower limbs. As a particular finding, IgG antibodies for COVID-19 were positive. Emergency cardiac surgery was performed. The mitral valve necessitated replacement with CarboMedics prosthesis. Unfortunately, the patient did not survive. Cunninghamella spp. was confirmed via the PCR analysis of vegetations. Cunninghamella endocarditis in the context of a systemic infection presented as an opportunistic infection affecting a child who had several risk factors. Mucormycosis is challenging to treat, with high mortality. Prophylactic treatment in beta-thalassemia patients with iron-chelator deprivation drugs, such as deferiprone, may help in preventing these particular fungal infections.

17.
Eur J Health Econ ; 2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35347553

RESUMO

BACKGROUND: Beta-thalassemia (BT) is an inherited blood disorder characterized by reduced levels of functional hemoglobin resulting in phenotypes ranging from clinically asymptomatic to severely anemic. Patients with BT may require lifelong regular blood transfusions supported by appropriate iron chelation therapy (ICT). This study aimed to determine how the UK general population values BT health states associated with differing transfusion burden and ICT. METHODS: Composite time trade-off (cTTO) methodology was employed to elicit health state utilities in BT. Relevant BT literature related to symptom and quality-of-life impact, including physical, functional, and emotional well-being, and safety profiles of BT treatments were considered when drafting health state descriptions. Eleven health state descriptions were developed and validated by hematologists and patient advocates for clinical accuracy and completeness. 200 individuals from the UK general population participated in the cTTO interviews. RESULTS: The mean age of participants was 41.50 years (SD 16.01, range 18-81); 88 (46.8%) were female. Utility values ranged from 0.78 (SD 0.34) for non-transfusion dependent BT with oral ICT to 0.37 (SD 0.50) for high transfusion burden with subcutaneous ICT in transfusion-dependent BT. CONCLUSIONS: This study provides health utilities for a range of BT health states from the UK general population perspective. Importantly, lower transfusion burden and lower burden of anemia were associated with higher utilities. To a lesser extent, differential modes of ICT were found to impact utility valuations in patients with BT. The utilities obtained in this study can be employed as inputs in cost-effectiveness analyses of BT therapies.

18.
Hematology ; 27(1): 353-359, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35287566

RESUMO

BACKGROUND: The discovery of circulating cell-free fetal DNA (cff-DNA) in maternal plasma has inspired the noninvasive prenatal testing (NIPT) approaches for various genetic fetal screening including rhesus D typing, sex determination, aneuploidies, and single-gene disorders. OBJECTIVE: Noninvasive determination of paternally inherited beta-thalassemia mutations in maternal total cell-free DNA (cf-DNA) by using allele-specific amplification refractory mutation system (ARMS) real-time PCR (RT-PCR) in concordance with the conventional invasive method. METHODS: An observational study was conducted at the Armed Forces Institute of Blood Transfusion in collaboration with the genetics resource center from March 2021 to August 2021. A total number of 26 couples were selected having a history of previously affected children with beta-thalassemia. A routine chorionic villus sampling (CVS) invasive procedure was carried out, and the mutation analysis was done using conventional PCR. To assess NIPT, a total cf-DNA was also extracted from maternal plasma and analyzed using allele-specific ARMS RT-PCR. RESULTS: Based on conventional PCR testing, 13 of 26 couples were found having beta-thalassemia carriers with homozygous mutation, and 13 couples were carriers with heterozygous mutations. Further to assess NIPT, the cf-DNA of 13 pregnant females among the couples with different mutational patterns was analyzed by allele-specific ARMS RT-PCR to detect paternally inherited mutations. In comparison with conventional PCR, 11 cases (84.6%) were matched successfully, while two cases (15.4%) had no concordance with conventional invasive prenatal testing (IPT). CONCLUSION: NIPT using maternal cf-DNA by allele-specific ARMS RT-PCR can be feasible to screen paternal inherited mutant alleles to rule out pregnant women from invasive procedures where the test would be negative for paternal inheritance. However, a low amount of fetal DNA in maternal plasma is a limiting factor and required further improvement to enrich fetal cf-DNA for complete concordance with conventional IPT.


Assuntos
Ácidos Nucleicos Livres , Teste Pré-Natal não Invasivo , Talassemia beta , Ácidos Nucleicos Livres/genética , Amostra da Vilosidade Coriônica , DNA , Feminino , Humanos , Mutação , Paquistão , Gravidez , Reação em Cadeia da Polimerase em Tempo Real , Talassemia beta/diagnóstico , Talassemia beta/genética
19.
Indian J Hematol Blood Transfus ; 38(1): 178-183, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35125727

RESUMO

Beta thalassemia major is associated with a subclinical hypercoagulable state. Endothelial activation markers like soluble Intercellular adhesion molecule (sICAM-1) and E-selectin have been implicated in the pathogenesis of endothelial dysfunction and hemostatic alterations. In this study we aimed to study serum levels of sICAM-1 and E-selectin in polytransfused children with ß thalassemia major and their association with serum ferritin and D-dimer levels. Sixty-two polytransfused ß-thalassemia major children aged between 5 and 17 years and 26 age and gender matched healthy controls were enrolled in the study. Complete blood count with peripheral smear, liver function tests, serum ferritin, coagulation tests [PT, APTT, D-dimer] and endothelial activation marker tests [ICAM-1 and E-selectin] were performed. PT, APTT and D-dimer levels were significantly higher in beta-thalassemia major patients than in control group (p = 0.003, p < 0.001, p < 0.001 respectively). Mean ICAM-1 and E-selectin levels were 731.34 ± 343.97 ng/ml and 111.75 ± 40.13 ng/ml respectively which were significantly higher than control group (p < 0.001, p < 0.001 respectively). No significant correlation of ICAM-1 and E-selectin was observed with serum ferritin, PT, APTT and D-dimer levels. The findings of the present study suggest that there is ongoing subclinical activation of coagulation cascade and fibrinolytic system in these patients. Endothelial activation markers may be used as early indicators of endothelial dysfunction to assess the thrombotic complications in beta thalassemia.

20.
AME Case Rep ; 6: 4, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35128312

RESUMO

The coexistence of alpha- and beta-thalassemia is not uncommon and neither is a single thalassemia subtype with a hemochromatosis H63D mutation, however the inheritance of all three diseases together has yet to be reported. We present this rare case of co-inherited alpha-thalassemia minor and beta-thalassemia minor initially misdiagnosed as iron deficiency anemia (IDA) in a reproductive aged female with a heterozygous H63D mutation. In our case report, a 27-year-old, Asian female presented with excessive lethargy and fatigue for the past 10 months. A year ago, she was prescribed Ferrous Sulfate 325 mg daily supplementation due to a suspicion of IDA secondary to a history of heavy menstruations. Although her reports displayed a low mean corpuscular volume (MCV) anemia, the patient declined therapy at that time due to abnormal labs, specifically regarding her urine and liver that subsequently lead to a hemochromatosis, heterozygous H63D diagnosis following genetic testing. Subsequently, the patient's anemia presenting in the setting of normal ferritin, high iron saturation, and elevated A2 fraction was most likely in accordance to carrying the alpha-thalassemia minor, beta-thalassemia minor, and heterozygous H63D gene mutations. Genetic testing further clarified two of the four alpha-globin genes were deleted, alpha3.7 and alpha4.2, consistent with alpha-thalassemia trait and a heterozygous, frameshift mutation of c.27dupG on the hemoglobin subunit beta (HBB) gene associated with beta-thalassemia minor. The initial diagnosis of IDA was inaccurate following the iron studies displaying normal ferritin levels. This is the first report of combined alpha- and beta-thalassemia with a hemochromatosis H63D mutation. Although the clinical presentation of our patient and laboratory values are stable, the course of inheriting all three diseases together is unknown and may inflate the risk of future complications beyond reported studies. Frequent monitorization of hemoglobin and iron studies will be conducted to follow this rare presentation and prevent life-threating iron overload.

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