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1.
BMC Pregnancy Childbirth ; 22(1): 16, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34986796

RESUMO

BACKGROUND: The Sustainable development goals, which focus strongly on equity, aim to end all forms of malnutrition by 2030. However, a significant cause of intergenerational transfer of malnutrition, anaemia in pregnancy, is still a challenge. It is especially so in the low- and middle-income settings where possible context-specific aetiologies leading to anaemia have been poorly explored. This study explores the prevalence of etiological factors significantly contributing to anaemia in pregnancy in Sri Lanka, a lower-middle-income country with a high prevalence of malnutrition albeit robust public health infrastructure. METHODS: All first-trimester pregnant women registered in the public maternal care programme in the Anuradhapura district from July to September 2019 were invited to participate in Rajarata Pregnancy Cohort (RaPCo). After a full blood count analysis, high-performance liquid chromatography, peripheral blood film examination, serum B12 and folate levels were performed in anaemic participants, guided by an algorithm based on the red cell indices in the full blood count. In addition, serum ferritin was tested in a random subsample of 213 participants. Anaemic women in this subsample underwent B12 and folate testing. RESULTS: Among 3127 participants, 14.4% (95%CI 13.2-15.7, n = 451) were anaemic. Haemoglobin ranged between 7.4 to 19.6 g/dl. 331(10.6%) had mild anaemia. Haemoglobin ≥13 g/dl was observed in 39(12.7%). Microcytic, normochromic-normocytic, hypochromic-normocytic and macrocytic anaemia was observed in 243(54%), 114(25.3%), 80(17.8%) and two (0.4%) of full blood counts in anaemic women, respectively. Microcytic anaemia with a red cell count ≥5 * 106 /µl demonstrated a 100% positive predictive value for minor haemoglobinopathies. Minor hemoglobinopathies were present in at least 23.3%(n = 105) of anaemic pregnant women. Prevalence of iron deficiency, B12 deficiency and Southeast Asian ovalocytosis among the anaemic was 41.9% (95%CI 26.4-59.2), 23.8% (95%CI 10.6-45.1) and 0.9% (95%CI 0.3-2.3%), respectively. Folate deficiency was not observed. CONCLUSION: Even though iron deficiency remains the primary cause, minor hemoglobinopathies, B 12 deficiency and other aetiologies substantially contribute to anaemia in pregnancy in this study population. Public health interventions, including screening for minor hemoglobinopathies and multiple micronutrient supplementation in pregnancy, should be considered in the national programme for areas where these problems have been identified.


Assuntos
Anemia/classificação , Anemia/epidemiologia , Anemia/etiologia , Complicações Hematológicas na Gravidez/classificação , Complicações Hematológicas na Gravidez/epidemiologia , Complicações Hematológicas na Gravidez/etiologia , Primeiro Trimestre da Gravidez , Adulto , Anemia/sangue , Estudos de Coortes , Índices de Eritrócitos , Feminino , Ferritinas/sangue , Deficiência de Ácido Fólico/complicações , Hemoglobinopatias/complicações , Hemoglobinas/análise , Humanos , Gravidez , Complicações Hematológicas na Gravidez/sangue , Prevalência , Sri Lanka/epidemiologia , Deficiência de Vitamina B 12/complicações
3.
BMC Genomics ; 22(1): 902, 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34915846

RESUMO

BACKGROUND: Sickle cell disease (SCD) is an important cause of under-five mortality. Tanzania is the 5th country in the world with the highest births prevalence of SCD individuals. Significant advances in the neonatal diagnosis of SCD using rapid point-of-care testing have been made. However genetic confirmation is still required for positive cases, in uncertain cases, in multiply transfused patients, to resolve compound heterozygosity (Hb S/ ß0 Thal or Hb S/ ß+ thal) not uncommon in the coastal regions of East Africa and increasingly also for pre-marital counselling and potentially for future curative approaches such as gene therapy. The currently available DNA tests are prohibitively expensive. Here, we describe an easy-to-use, affordable and accurate ß-globin sequencing approach that can be easily integrated within existing NBS for SCD and other haemoglobinopathies especially in Low- and Middle-income Countries. AIM: To evaluate an affordable DNA technology for the diagnosis of Sickle cell disease and other haemoglobinopathies in a resource-limited setting. METHODS: Laboratory-based validation study was conducted by Muhimbili University of Health and Allied Sciences and the University of Oxford involving sequencing of the entire ß -haemoglobin locus using the Oxford Nanopore MinION platform. A total number of 36 Dried blood spots and whole blood samples were subjected to conventional protein-based methods (isoelectric focusing, HPLC), and/or sequenced by the Sanger method as comparators. RESULTS: Sequencing results for SCD using the MinION were 100% concordant with those from the Sanger method. In addition, the long-read DNA sequencing method enabled the resolution of cases with unusual phenotypes which make up 1% of all children in Tanzania. The cost is £11/ sample for consumables, which is cheaper compared to other sequencing platforms. CONCLUSIONS: This is the first report of a comprehensive single DNA assay as a definitive diagnostic test for SCD and other haemoglobinopathies. The test is fast, precise, accurate and affordable.


Assuntos
Anemia Falciforme , Hemoglobinopatias , Anemia Falciforme/diagnóstico , Anemia Falciforme/genética , DNA , Testes Diagnósticos de Rotina , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/genética , Humanos , Tanzânia
4.
Orphanet J Rare Dis ; 16(1): 415, 2021 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627331

RESUMO

Congenital hemolytic anemias (CHAs) comprise defects of the erythrocyte membrane proteins and of red blood cell enzymes metabolism, along with alterations of erythropoiesis. These rare and heterogeneous conditions may generate several difficulties from the diagnostic point of view. Membrane defects include hereditary spherocytosis and elliptocytosis, and the group of hereditary stomatocytosis; glucose-6-phosphate dehydrogenase and pyruvate kinase, are the most common enzyme deficiencies. Among ultra-rare forms, it is worth reminding other enzyme defects (glucosephosphate isomerase, phosphofructokinase, adenylate kinase, triosephosphate isomerase, phosphoglycerate kinase, hexokinase, and pyrimidine 5'-nucleotidase), and congenital dyserythropoietic anemias. Family history, clinical findings (anemia, hemolysis, splenomegaly, gallstones, and iron overload), red cells morphology, and biochemical tests are well recognized diagnostic tools. Molecular findings are increasingly used, particularly in recessive and de novo cases, and may be fundamental in unraveling the diagnosis. Notably, several confounders may further challenge the diagnostic workup, including concomitant blood loss, nutrients deficiency, alterations of hemolytic markers due to other causes (alloimmunization, infectious agents, rare metabolic disorders), coexistence of other hemolytic disorders (autoimmune hemolytic anemia, paroxysmal nocturnal hemoglobinuria, etc.). Additional factors to be considered are the possible association with bone marrow, renal or hepatic diseases, other causes of iron overload (hereditary hemochromatosis, hemoglobinopathies, metabolic diseases), and the presence of extra-hematological signs/symptoms. In this review we provide some instructive clinical vignettes that highlight the difficulties and confounders encountered in the diagnosis and clinical management of CHAs.


Assuntos
Anemia Hemolítica Congênita , Hemoglobinopatias , Esferocitose Hereditária , Anemia Hemolítica Congênita/diagnóstico , Anemia Hemolítica Congênita/genética , Eritrócitos , Humanos , Piruvato Quinase/genética , Esferocitose Hereditária/diagnóstico , Esferocitose Hereditária/genética
5.
Rev Prat ; 71(6): 653-658, 2021 Jun.
Artigo em Francês | MEDLINE | ID: mdl-34553565

RESUMO

For a better biological management of diabetes for patients with hemoglobinopathy. Glycated hemoglobin, HbA1c, as a cumulative retrospective marker of glycemic control in diabetic patients could be faulty in patients with hemoglobinopathy. Abnormal hemoglobin could introduce bias analytically during HbA1c measure but also due to its physiopathology by altering the lifespan of red blood cells and/or the normal glycation process. The aim of this communication is to raise awareness of physicians on some important elements for an appropriate interpretation of HbA1c levels so that these patients are better diagnosed and balanced. This review enlightens the practitioner on the HbA1c assay methods (separatives) to prioritize. It provides him critical situations where inconsistent HbA1c results should lead him to suspect hemoglobinopathy, what to do in terms of additional investigations and follow-up. It also offers a pragmatic solution for relevant personalized follow-up. Clinico-biological collaboration will help determine the HbA1c target to be reached.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Hemoglobinopatias , Glicemia , Diabetes Mellitus/terapia , Hemoglobina A Glicada/análise , Hemoglobinopatias/terapia , Humanos , Masculino , Estudos Retrospectivos
6.
Acta Biomed ; 92(4): e2021410, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34487057

RESUMO

Sickle cell disease (SCD) and thalassemias are the most common monogenic diseases in the world. The number of migrants and refugees in Europe and Turkey, in the past decade, has increased dramatically due to war, violence or prosecutions in their homeland. Prevention and management of haemoglobin disorders is well established and managed in countries where these conditions were traditionally endemic or in countries that have a longstanding tradition of receiving migrants. Therefore, preventive and diagnostic programmes regarding hemoglobinopathies in immigrant populations have been implemented. The purpose of this paper it to report a summary of the experience gained in Italy, Spain and Turkey in migrants, asylum seekers and refugees.


Assuntos
Emigração e Imigração , Hemoglobinopatias , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/epidemiologia , Humanos , Itália , Espanha , Turquia/epidemiologia
7.
Acta Biomed ; 92(4): e2021410, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34487058

RESUMO

Starting from 2021, Acta Biomedica Parmensis will dedicate an annual update to the "Advances in Hemoglobinopathies". The section editor of this new editorial initiative is prof. Ashraf T Soliman, Pediatrician and Endocrinologist at Hamad Medical Center (HMC) of Doha. Prof Soliman is a pionier in the study of endocrine complications in hemoglobinopathies and effects of blood transfusions on spermatogenesis. He collaborates strictly with prof. Mohamed Yassin, Hematologist-Oncologist at MCH and the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A). This issue of Acta Biomedica contains three articles on: The different patterns of insulin response during Oral Glucose Tolerance Test (OGTT) in transfused young patients with ß- Thalassemia; Immigration and screening programs for hemoglobinopathies in Italy, Spain and Turkey and The effects of treatment with blood transfusion, iron chelation and hydroxyurea on puberty, growth and spermatogenesis in sickle cell disease,.


Assuntos
Anemia Falciforme , Hemoglobinopatias , Talassemia , Talassemia beta , Emigração e Imigração , Hemoglobinopatias/terapia , Humanos , Masculino , Talassemia beta/terapia
8.
Respir Med ; 187: 106597, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34481306

RESUMO

Based on computerized modeling studies, it has been postulated that the severe hypoxemia in COVID-19 may result from impaired oxygen carrying capacity on hemoglobin. Standard pulse oximetry may not detect hypoxemia resulting from hemoglobinopathy, therefore hemoglobin co-oximetry is needed to evaluate this divergence. In a clinical data analysis of a multicenter cohort of hospitalized patients with COVID-19, we found a minimal effect, less than 1%, on the correlation between oxyhemoglobin concentration and predicted oxygen saturation in the presence of COVID-19 infection. This effect is unlikely to explain the clinically significant hypoxia in COVID-19 patients.


Assuntos
COVID-19 , Hemoglobinopatias , Humanos , Hipóxia , Oximetria , Oxigênio , Oxiemoglobinas/análise , SARS-CoV-2
9.
Elife ; 102021 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-34585664

RESUMO

Mutations in the adult ß-globin gene can lead to a variety of hemoglobinopathies, including sickle cell disease and ß-thalassemia. An increase in fetal hemoglobin expression throughout adulthood, a condition named hereditary persistence of fetal hemoglobin (HPFH), has been found to ameliorate hemoglobinopathies. Deletional HPFH occurs through the excision of a significant portion of the 3' end of the ß-globin locus, including a CTCF binding site termed 3'HS1. Here, we show that the deletion of this CTCF site alone induces fetal hemoglobin expression in both adult CD34+ hematopoietic stem and progenitor cells and HUDEP-2 erythroid progenitor cells. This induction is driven by the ectopic access of a previously postulated distal enhancer located in the OR52A1 gene downstream of the locus, which can also be insulated by the inversion of the 3'HS1 CTCF site. This suggests that genetic editing of this binding site can have therapeutic implications to treat hemoglobinopathies.


Assuntos
Fator de Ligação a CCCTC/metabolismo , Hemoglobina Fetal/genética , Regulação da Expressão Gênica , Hemoglobinopatias/genética , Globinas beta/genética , Sítios de Ligação , Fator de Ligação a CCCTC/genética , Células-Tronco Hematopoéticas/metabolismo , Hemoglobinopatias/metabolismo , Humanos , Mutação , Ligação Proteica , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Globinas beta/metabolismo
10.
J Med Case Rep ; 15(1): 386, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34334128

RESUMO

BACKGROUND: Hemoglobin S and E are commonly occurring hemoglobin variants among distinctly separate tribal populations of Central and Northeast India, respectively. Combined heterozygosity for hemoglobin S and E or hemoglobin SE disease is a benign clinical condition with rare incidence. Reports of approximately 46 hemoglobin SE cases are available worldwide. We conducted a screening program to study the prevalence of hemoglobin variants among the tribal population working in the tea estates of Northeast India. A total of 551 subjects were screened, and complete blood count was performed. Based on their hematological profiles, hemoglobin typing was done for 218 subjects. CASE PRESENTATION: We describe a case of an adolescent male of Munda tribe diagnosed as double heterozygous for hemoglobin S and E. On screening of the nuclear family of the subject, the mother was found to have hemoglobin E disease and father as hemoglobin S trait. Both siblings of the subject were diagnosed as hemoglobin E trait. CONCLUSION: This is the first case of compound heterozygous for hemoglobin S and E to be reported from the tea tribes of Assam, India.


Assuntos
Hemoglobina E , Hemoglobinopatias , Traço Falciforme , Adolescente , Hemoglobina E/genética , Hemoglobina Falciforme , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/genética , Humanos , Índia , Masculino
11.
Indian J Pathol Microbiol ; 64(3): 518-523, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34341263

RESUMO

Background: : HPLC is one of the most important tools for accurate diagnosis of hemoglobinopathies and thalassemias. The advantage of the HPLC system is the excellent resolution, reproducibility &quantification of several normal and abnormal hemoglobin. Results: BIO RAD Variant II analyzer was used. Sickle cell syndromes including double heterozygous states accounted for 56.13% of total cases. HbSS, HbS/ß0-th, HbS/ß+-th ß-thal trait comprises 29%, 6.5%, 5.1%& 10% of total cases respectively with mean MCV (fl) = 84, 68,71,64 respectively. The Mean HbA2 for ß-thal trait, HbE trait &HbE-ß thal showed 5.1 ± 1.1, 19 ± 9 & 24 ± 8 respectively. HbF is increased in 8.6% case (excluding SC syndromes & ß-thal disorders), of these 5.5% were infants & 12 cases of Aplastic Anemias. Peak P2 >7% (2.4% cases) was seen in uncontrolled diabetes mellitus which on quantification showed HbA1C = 8 ± 2.1 mmol/L. Discussion: : HPLC in correlation with CBC parameters & family studies can aid in the diagnosis of majority of Hemoglobinopathies and thalassemic syndrome. The CBC & HPLC parameters of the present study are in good correlation with the research conducted by Tejinder Sing, RiouJ & Alla Joutovsky. Present study showed HPLC comprehensively characterizing HbS, A, A2, F, S, C, D from each other & was also applicable for the quantification of HbA1c for the monitoring of Diabetes Mellitus. Conclusion: : The merits of HPLC are small quantity of sample required, economical, less TAT, accurate categorization of HbS, HbA2 & F. But one has to be aware of the limitations and problems associated with this method due to variant hemoglobin within the same retention windows. The present findings show HPLC as an excellent & powerful diagnostic tool for the direct identification of hemoglobin variants with a high degree of precision in the quantification of normal and abnormal hemoglobin fractions.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , Hemoglobinopatias/diagnóstico , Hemoglobinas Anormais/análise , Talassemia/diagnóstico , Cromatografia Líquida de Alta Pressão/economia , Hemoglobinopatias/sangue , Humanos , Fenótipo , Reprodutibilidade dos Testes , Estudos Retrospectivos , Síndrome , Talassemia/sangue
14.
PLoS One ; 16(7): e0251576, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34228734

RESUMO

The Mediterranean hemopathic syndromes (MHS) are the most prevalent hemoglobinopathies in the Mediterranean basin. Transfusion therapy is the main therapy for these disorders, particularly for severe forms of the disease. Currently, pre-transfusion serological typing of erythrocyte antigens is the standard tool for reducing complications of transfusion in those patients. This study compared genotyping with phenotyping of non-ABO erythrocyte antigens in patients with MHS and assessed the effect of transfusion therapy on their results. One-hundred ninety-eight MHS patients were recruited, screened, and proven negative for allo-antibodies. They were grouped into two groups: (1) 20 newly diagnosed patients with no transfusion history and (2) 178 previously diagnosed patients undergoing transfusion therapy. Patients were interviewed and clinically examined. Full blood count (FBC) and high performance liquid chromatography (HPLC) were done for group 1 only. Genotyping and phenotyping of non-ABO erythrocyte antigens were performed for group 1, and 25 patients out of group 2 were propensity score-matched (PSM) with group 1. Both groups were gender and age matched; 55% and 74% of groups 1 and 2 had major disease, respectively. Insignificant differences were observed between genotyping and phenotyping of non-ABO erythrocyte antigens in group 1, while significant discrepancies and mixed field results were noted in group 2 patients. Discrepancies were obvious with JKa, JKb, and little c antigens. Conclusively, molecular typing is a powerful tool for pre-transfusion testing in chronically transfused MHS patients. This testing reduces incidence of transfusion reactions. JKa, JKb and little c antigens are the most clinically significant non-ABO erythrocyte antigens.


Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Genótipo , Hemoglobinopatias/imunologia , Fenótipo , Adulto , Humanos , Masculino
15.
Int J Lab Hematol ; 43(4): 845-852, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34060242

RESUMO

INTRODUCTION: Hemoglobin (Hb) analysis is a key testing for diagnosis of hemoglobinopathies. Accurate analysis, interpretation of results, and genetic risk assessment are important. We report on 8 years of the proficiency testing (PT) program for hemoglobinopathies in Thailand. METHODS: Laboratory participants were required to test two simulated PT items in each cycle using capillary electrophoresis, one was a husband and another was his pregnant wife. Related hematological parameters were provided. The participants also provide interpretation and evaluate the risk of having three severe thalassemia diseases in an expected fetus. Three cycles were operated per year in accordance with the ISO17043 and ISO13528 guidelines. A total of 84 laboratories throughout Thailand were participated. RESULTS: A total of 24 PT cycles were performed during 2012-2019. Most participants had Excellent performance for the PT items with normal, ß-thalassemia trait, hemoglobin E trait, hemoglobin E trait with α-thalassemia, and Hb H disease. However, when the PT items with homozygous Hb E and Hb E-ß-thalassemia were tested, an increase in a Needs improvement performance was noted. From 24 PT cycles, the performance with Excellent, Good, Fair, and Needs improvement was ranging from 10.5%-95.8%, 0%-11.3%, 0%-77.2%, and 2.3%-37.0%, respectively. CONCLUSION: Most participants have proven their performance to be reliable and demonstrated their abilities to provide interpretation and genetic risk assessment on most of the PT items. For complex thalassemia however, a need to improve the interpretation and risk assessment skills is required which is essential for effective prevention and control of severe thalassemia diseases in Thailand.


Assuntos
Hemoglobinopatias/diagnóstico , Talassemia/diagnóstico , Eletroforese Capilar , Feminino , Testes Genéticos , Hemoglobina E/genética , Hemoglobinopatias/epidemiologia , Hemoglobinopatias/genética , Homozigoto , Humanos , Ensaio de Proficiência Laboratorial , Gravidez , Diagnóstico Pré-Natal , Tailândia/epidemiologia , Talassemia/epidemiologia , Talassemia/genética
16.
Prog Mol Biol Transl Sci ; 182: 153-183, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34175041

RESUMO

ß-hemoglobinopathies are the most common monogenic disorders worldwide and are caused by mutations in the ß-globin locus altering the production of adult hemoglobin (HbA). Transplantation of autologous hematopoietic stem cells (HSCs) corrected by lentiviral vector-mediated addition of a functional ß-like globin raised new hopes to treat sickle cell disease and ß-thalassemia patients; however, the low expression of the therapeutic gene per vector copy is often not sufficient to fully correct the patients with a severe clinical phenotype. Recent advances in the genome editing field brought new possibilities to cure ß-hemoglobinopathies by allowing the direct modification of specific endogenous loci. Double-strand breaks (DSBs)-inducing nucleases (i.e., ZFNs, TALENs and CRISPR-Cas9) or DSB-free tools (i.e., base and prime editing) have been used to directly correct the disease-causing mutations, restoring HbA expression, or to reactivate the expression of the fetal hemoglobin (HbF), which is known to alleviate clinical symptoms of ß-hemoglobinopathy patients. Here, we describe the different genome editing tools, their application to develop therapeutic approaches to ß-hemoglobinopathies and ongoing clinical trials using genome editing strategies.


Assuntos
Hemoglobinopatias , Talassemia beta , Hemoglobina Fetal/genética , Edição de Genes , Hemoglobinopatias/genética , Hemoglobinopatias/terapia , Humanos , Globinas beta/genética , Talassemia beta/genética , Talassemia beta/terapia
17.
Saudi Med J ; 42(7): 784-789, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34187923

RESUMO

OBJECTIVES: To investigate trends in hemoglobinopathies following the establishment of a mandatory premarital screening program (MPMSP) in the southern region of Saudi Arabia, where they are considered highly predominant. METHODS: A retrospective analysis was performed on data from 32,130 high-performance liquid chromatography (HPLC) tests between November 2017 and October 2020. The data was obtained from the Hematology section, Laboratory Department, Armed Forces Hospital, Southern Region. RESULTS: Despite the establishment of the MPMSP, our data showed that sickle cell disease remains a predominant hemoglobinopathy accounting for more than 7% of total tests in Southern Saudi Arabia. Observed HPLC hemoglobin fractions among the tested population showed a reduction in Hb A mean indicating a high rate of hemoglobin abnormalities. In addition, the prevalence of hemoglobin variants, including sickle cell and thalassemia, was higher in the younger population born after the MPMSP than in older subjects. CONCLUSION: Even with the implementation of the MPMSP, hemoglobin abnormalities remain prevalent in southern Saudi Arabia. A longer time frame is recommended to verify the validity of the program.


Assuntos
Hemoglobinopatias , Talassemia beta , Idoso , Hemoglobinopatias/epidemiologia , Humanos , Prevalência , Estudos Retrospectivos , Arábia Saudita/epidemiologia
18.
Haematologica ; 106(9): 2304-2311, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34042406

RESUMO

Patients with inherited anemia and hemoglobinopathies (such as sickle cell disease and ß-thalassemia) are treated with red blood cell (RBC) transfusions to alleviate their symptoms. Some of these patients may have rare blood group types or go on to develop alloimmune reactions, which can make it difficult to source compatible blood in the donor population. Laboratory-grown RBC represent a particularly attractive alternative which could satisfy an unmet clinical need. The challenge, however, is to produce - from a limited number of stem cells - the 2x1012 RBC required for a standard adult therapeutic dose. Encouraging progress has been made in RBC production from adult stem cells under good manufacturing practice. In 2011, the Douay group conducted a successful proof-of-principle mini-transfusion of autologous manufactured RBC in a single volunteer. In the UK, a trial is planned to assess whether manufactured RBC are equivalent to RBC produced naturally in donors, by testing an allogeneic mini-dose of laboratory-grown manufactured RBC in multiple volunteers. This review discusses recent progress in the erythroid culture field as well as opportunities for further scaling up of manufactured RBC production for transfusion practice.


Assuntos
Anemia Falciforme , Hemoglobinopatias , Anemia Falciforme/terapia , Transfusão de Sangue , Transfusão de Eritrócitos , Eritrócitos , Humanos
19.
Bone Marrow Transplant ; 56(9): 2203-2211, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33941871

RESUMO

The use of HLA-mismatched (un)related donors is historically associated with a higher incidence of transplant-related complications and mortality. However, the use of such donors may overcome the limited availability of HLA-matched donors for patients with ß-thalassemia major (TM) and sickle cell disease (SCD). We investigated hematopoietic stem cell transplantation (HSCT) outcomes of pediatric TM and SCD patients treated with a mismatched donor using a treosulfan-based conditioning in combination with ATG and post-transplant cyclophosphamide (PT-CY) and compared these results to the clinical outcome of patients treated by matched donor HSCT without PT-CY. Thirty-eight children (n = 24 HLA-identical or 10/10-matched donors; n = 14 HLA-mismatched donors), who received a non-depleted bone marrow graft were included. Event-free survival (EFS) and GvHD were not higher in the mismatched PT-Cy group as compared to the matched group. Moreover, despite delayed neutrophil engraftment (day +22 vs. +26, p = 0.002) and immune recovery in the mismatched PT-Cy group, this did not result in more infectious complications. Therefore, we conclude that in the absence of an HLA-identical or a matched unrelated donor, HSCT with a mismatched unrelated or haploidentical donor in combination with ATG plus PT-CY can be considered a safe and effective treatment option for pediatric hemoglobinopathy patients.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Hemoglobinopatias , Criança , Ciclofosfamida/uso terapêutico , Hemoglobinopatias/terapia , Humanos , Condicionamento Pré-Transplante
20.
Clin Chim Acta ; 519: 193-197, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33939955

RESUMO

BACKGROUND: Hemoglobin fractionation by capillary zone electrophoresis (CE) is becoming a popular method for the identification of hemoglobin variants that can cause hemoglobinopathies. The goal of this study was to compare the performance of capillary electrophoresis using Sebia Capillarys 2 Flex Piercing system (CE-S) with high-pressure liquid chromatography (HPLC) using Primus Ultra2 Resolution Variants System (HPLC-P) as a primary method in hemoglobinopathy work-up. METHODS: A total of 306 blood specimens submitted for evaluation of hemoglobinopathies were studied using HPLC-P and CE-S. RESULTS: The reference ranges for Hb A, A2 and F agreed well between methods. All common variants containing Hb S and Hb C were detected by both methods. Quantification of Hb A2 with HPLC-P required a correction in the presence of Hb S, while quantification of Hb A2 was slightly overestimated by CE-S in the presence of Hb C. Of 41 samples containing other variants, 2 were not identified by HPLC-P and 3 were not identified by CE-S. CONCLUSION: CE-S provides comparable information to that obtained by HPLC-P and it is a reliable primary method for the evaluation of hemoglobin variants.


Assuntos
Hemoglobinopatias , Hemoglobinas Anormais , Cromatografia Líquida de Alta Pressão , Eletroforese Capilar , Hemoglobina A Glicada/análise , Testes Hematológicos , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/genética , Hemoglobinas/análise , Hemoglobinas Anormais/análise , Humanos
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