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Wendt AS, Brintrup J, Waid JL, Kader A, Lambrecht NJ, Gabrysch S. Thalassemia and hemoglobinopathy prevalence in a community-based sample in Sylhet, Bangladesh. Orphanet J Rare Dis 2023; 18:192. [PMID: 37468973 PMCID: PMC10355052 DOI: 10.1186/s13023-023-02821-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 07/10/2023] [Indexed: 07/21/2023] Open
Abstract
BACKGROUND Inherited blood disorders affect 7% of the population worldwide, with higher prevalences in countries in the "thalassemia belt," which includes Bangladesh. Clinical management options for severely affected individuals are expensive; thus, targeted government policies are needed to support prevention and treatment programs. In Bangladesh, there is a lack of data, in particular community-based estimates, to determine population prevalence. This study aims to estimate the prevalence of a wide range of hemoglobinopathies and their associations with anemia in a community-based sample of women and young children in rural Sylhet, Bangladesh. METHODS Capillary blood samples from 900 reproductive-aged women and 395 children (aged 6-37 months) participating in the Food and Agricultural Approaches to Reducing Malnutrition (FAARM) trial in two sub-districts of Habiganj, Sylhet Division, Bangladesh were analyzed for alpha thalassemia, beta thalassemia, and other hemoglobinopathies. We examined the association of each inherited blood disorder with hemoglobin concentration and anemia using linear and logistic regression. RESULTS We identified at least one inherited blood disorder in 11% of women and 10% of children. Alpha thalassemia was most prevalent, identified in 7% of women and 5% of children, followed by beta thalassemia and hemoglobin E in 2-3%. We also identified cases of hemoglobin S and hemoglobin D in this population. Having any of the identified inherited blood disorders was associated with lower hemoglobin values among non-pregnant women, largely driven by alpha and beta thalassemia. Pregnant women with beta thalassemia were also more likely to have lower hemoglobin concentrations. Among children, we found weak evidence for a relationship between hemoglobinopathy and lower hemoglobin concentrations. CONCLUSIONS We found a high prevalence of alpha thalassemia among both women and children in rural Sylhet, Bangladesh-higher than all other identified hemoglobinopathies combined. Community-based estimates of alpha thalassemia prevalence in Bangladesh are scarce, yet our findings suggest that alpha thalassemia may comprise the majority of inherited blood disorders in some regions of the country. We recommend that future research on inherited blood disorders in Bangladesh include estimates of alpha thalassemia in their reporting for public health awareness and to facilitate couples counseling.
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Affiliation(s)
- Amanda S Wendt
- Research Department 2, Potsdam Institute for Climate Impact Research (PIK), Member of the Leibniz Association, Potsdam, Germany.
- Heidelberg Institute of Global Health, Heidelberg University, Heidelberg, Germany.
| | - Joaquin Brintrup
- Hemoglobin Laboratory, Department of Pediatrics, University Hospital Ulm, Ulm, Germany
| | - Jillian L Waid
- Research Department 2, Potsdam Institute for Climate Impact Research (PIK), Member of the Leibniz Association, Potsdam, Germany
- Heidelberg Institute of Global Health, Heidelberg University, Heidelberg, Germany
- Bangladesh Country Office, Helen Keller International, Dhaka, Bangladesh
| | - Abdul Kader
- Bangladesh Country Office, Helen Keller International, Dhaka, Bangladesh
| | - Nathalie J Lambrecht
- Research Department 2, Potsdam Institute for Climate Impact Research (PIK), Member of the Leibniz Association, Potsdam, Germany
- Institute of Public Health, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany
| | - Sabine Gabrysch
- Research Department 2, Potsdam Institute for Climate Impact Research (PIK), Member of the Leibniz Association, Potsdam, Germany
- Heidelberg Institute of Global Health, Heidelberg University, Heidelberg, Germany
- Institute of Public Health, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany
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Young MF, Oaks BM, Rogers HP, Tandon S, Martorell R, Dewey KG, Wendt AS. Maternal low and high hemoglobin concentrations and associations with adverse maternal and infant health outcomes: an updated global systematic review and meta-analysis. BMC Pregnancy Childbirth 2023; 23:264. [PMID: 37076797 PMCID: PMC10114461 DOI: 10.1186/s12884-023-05489-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 03/02/2023] [Indexed: 04/21/2023] Open
Abstract
BACKGROUND Growing evidence suggests low and high maternal hemoglobin (Hb) concentrations may have adverse consequences for maternal and child health. There remain questions on specific Hb thresholds to define anemia and high Hb as well as how cutoffs may vary by anemia etiology and timing of assessment. METHODS We conducted an updated systematic review (using PubMed and Cochrane Review) on low (< 110 g/L) and high (≥ 130 g/L) maternal Hb concentrations and associations with a range of maternal and infant health outcomes. We examined associations by timing of Hb assessment (preconception; first, second, and third trimesters, as well as at any time point in pregnancy), varying cutoffs used for defining low and high hemoglobin concentrations and performed stratified analyses by iron-deficiency anemia. We conducted meta-analyses to obtain odds ratios (OR) and 95% confidence intervals. RESULTS The updated systematic review included 148 studies. Low maternal Hb at any time point in pregnancy was associated with: low birthweight, LBW (OR (95% CI) 1.28 (1.22-1.35)), very low birthweight, VLBW (2.15 (1.47-3.13)), preterm birth, PTB (1.35 (1.29-1.42)), small-for-gestational age, SGA (1.11 (1.02-1.19)), stillbirth 1.43 (1.24-1.65)), perinatal mortality (1.75 (1.28-2.39)), neonatal mortality (1.25 (1.16-1.34), postpartum hemorrhage (1.69 (1.45-1.97)), transfusion (3.68 (2.58-5.26)), pre-eclampsia (1.57 (1.23-2.01)), and prenatal depression (1.44 (1.24-1.68)). For maternal mortality, the OR was higher for Hb < 90 (4.83 (2.17-10.74)) than for Hb < 100 (2.87 (1.08-7.67)). High maternal Hb was associated with: VLBW (1.35 (1.16-1.57)), PTB (1.12 (1.00-1.25)), SGA (1.17 (1.09-1.25)), stillbirth (1.32 (1.09-1.60)), maternal mortality (2.01 (1.12-3.61)), gestational diabetes (1.71 (1.19-2.46)), and pre-eclampsia (1.34 (1.16-1.56)). Stronger associations were noted earlier in pregnancy for low Hb and adverse birth outcomes while the role of timing of high Hb was inconsistent. Lower Hb cutoffs were associated with greater odds of poor outcomes; for high Hb, data were too limited to identify patterns. Information on anemia etiology was limited; relationships did not vary by iron-deficiency anemia. CONCLUSION Both low and high maternal Hb concentrations during pregnancy are strong predictors of adverse maternal and infant health outcomes. Additional research is needed to establish healthy reference ranges and design effective interventions to optimize maternal Hb during pregnancy.
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Affiliation(s)
- Melissa F Young
- Hubert Department of Global Health, Emory University, 1518 Clifton Road NE, 30322, Atlanta, GA, USA.
| | - Brietta M Oaks
- Department of Nutrition and Food Sciences, University of Rhode Island, 02881, Kingston, United States
| | - Hannah Paige Rogers
- Hubert Department of Global Health, Emory University, 1518 Clifton Road NE, 30322, Atlanta, GA, USA
| | - Sonia Tandon
- Hubert Department of Global Health, Emory University, 1518 Clifton Road NE, 30322, Atlanta, GA, USA
| | - Reynaldo Martorell
- Hubert Department of Global Health, Emory University, 1518 Clifton Road NE, 30322, Atlanta, GA, USA
| | - Kathryn G Dewey
- Department of Nutrition, University of California, Davis, 95616, Davis, United States
| | - Amanda S Wendt
- Research Department 2, Potsdam Institute for Climate Impact Research (PIK), Member of the Leibniz Association, PO Box 60 12 03, 14412,, Potsdam, Germany
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Is the Role of Hepcidin and Erythroferrone in the Pathogenesis of Beta Thalassemia the Key to Developing Novel Treatment Strategies? THALASSEMIA REPORTS 2022. [DOI: 10.3390/thalassrep12030017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Thalassemia is a disease of erythrocytes that varies largely on its genetic composition and associated clinical presentation. Though some patients may remain asymptomatic, those with a complicated course may experience severe anemia early in childhood, carrying into adulthood and requiring recurrent blood transfusions as a pillar of symptom management. Due to the consequences of ineffective erythropoiesis and frequent transfusions, patients with severe beta thalassemia may be subsequently susceptible to hemochromatosis. In light of the established role of hepcidin and erythroferrone in the pathogenesis of beta thalassemia, this review aims to discuss current clinical trials and studies in the field while presenting clinical implications of the HAMP gene polymorphisms and novel treatments. Research suggested incorporating erythroferrone and serum hepcidin testing as a part of routine workups for beta thalassemia, as they could be a predictive tool for early iron accumulation. Furthermore, ameliorating low hepcidin and high erythroferrone appeared to be crucial in treating beta thalassemia and its complications due to iron overload. Currently, hepcidin-like compounds, such as minihepcidins, LJPC-401, PTG-300, VIT-2763, and agents that promote hepcidin production by inhibiting TMPRSS6 expression or erythroferrone, were shown to be effective in restoring iron homeostasis in preliminary studies. Moreover, the natural bioactives astragalus polysaccharide and icariin have been recently recognized as hepcidin expression inductors.
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Chen N, Li Z, Huang Y, Xiao C, Shen X, Pan S, Su Q, Wang Z. Iron parameters in pregnant women with beta-thalassaemia minor combined with iron deficiency anaemia compared to pregnant women with iron deficiency anaemia alone demonstrate the safety of iron supplementation in beta-thalassaemia minor during pregnancy. Br J Haematol 2021; 196:390-396. [PMID: 34562018 DOI: 10.1111/bjh.17827] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 08/26/2021] [Accepted: 08/27/2021] [Indexed: 12/29/2022]
Abstract
In patients with beta-thalassaemia intermedia or major, hepcidin induces iron overload by continuously promoting iron absorption. There have been no studies in pregnant women with beta-thalassaemia minor combined with iron deficiency anaemia (IDA), examining whether hepcidin is inhibited by GDF15, as may occur in patients with beta-thalassaemia intermedia or major, or whether the iron metabolism characteristics and the effect of iron supplementation are consistent with simple IDA in pregnancy. We compared and analysed routine blood parameters, iron metabolism parameters, the GDF15 levels, and the hepcidin levels among four groups, namely the beta-thalassaemia (β) + IDA, β, IDA, and normal groups. In addition, the β + IDA and IDA groups received iron supplementation for four weeks. We found no statistically significant correlation between hepcidin and GDF15 in any group, but a positive correlation was observed between hepcidin and ferritin. After iron supplementation, the routine blood parameters and iron metabolism parameters in the β + IDA group were improved, and the hepcidin content was significantly increased. These results suggest that in pregnant women with beta-thalassaemia minor, hepcidin functions normally to maintain iron homeostasis, and that iron supplementation is effective and safe.
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Affiliation(s)
- Niankun Chen
- The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Zhongjun Li
- Department of Obstetrics and Gynecology, Dongguan People's Hospital of Southern Medical University, Dongguan, China
| | - Yingying Huang
- Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Chaoqun Xiao
- Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xinyang Shen
- Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shumin Pan
- Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Qiongqiong Su
- Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Zhijian Wang
- Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Ineffective Erythropoiesis in β-Thalassaemia: Key Steps and Therapeutic Options by Drugs. Int J Mol Sci 2021; 22:ijms22137229. [PMID: 34281283 PMCID: PMC8268821 DOI: 10.3390/ijms22137229] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 06/29/2021] [Accepted: 06/30/2021] [Indexed: 01/19/2023] Open
Abstract
β-thalassaemia is a rare genetic condition caused by mutations in the β-globin gene that result in severe iron-loading anaemia, maintained by a detrimental state of ineffective erythropoiesis (IE). The role of multiple mechanisms involved in the pathophysiology of the disease has been recently unravelled. The unbalanced production of α-globin is a major source of oxidative stress and membrane damage in red blood cells (RBC). In addition, IE is tightly linked to iron metabolism dysregulation, and the relevance of new players of this pathway, i.e., hepcidin, erythroferrone, matriptase-2, among others, has emerged. Advances have been made in understanding the balance between proliferation and maturation of erythroid precursors and the role of specific factors in this process, such as members of the TGF-β superfamily, and their downstream effectors, or the transcription factor GATA1. The increasing understanding of IE allowed for the development of a broad set of potential therapeutic options beyond the current standard of care. Many candidates of disease-modifying drugs are currently under clinical investigation, targeting the regulation of iron metabolism, the production of foetal haemoglobin, the maturation process, or the energetic balance and membrane stability of RBC. Overall, they provide tools and evidence for multiple and synergistic approaches that are effectively moving clinical research in β-thalassaemia from bench to bedside.
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Ismail UN, Azlan CA, Khairullah S, Azman RR, Omar NF, Md Shah MN, Yeong CH, Jackson N, Ng KH. Marrow Fat Content and Composition in β-Thalassemia: A Study using 1 H-MRS. J Magn Reson Imaging 2020; 53:190-198. [PMID: 33237616 DOI: 10.1002/jmri.27294] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 07/01/2020] [Accepted: 07/06/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND β-thalassemia is a genetic disease that causes abnormal production of red blood cells (ineffective erythropoiesis, IE). IE is a condition known to change bone marrow composition. PURPOSE To evaluate the effect of IE on the marrow fat content and fat unsaturation levels in the proximal femur using 1 H-MRS. STUDY TYPE Prospective. SUBJECTS Twenty-three subjects were included in this study, seven control and 16 β-thalassemia subjects. FIELD STRENGTH/SEQUENCE 3.0T; stimulated echo acquisition Mode (STEAM); magnetic resonance spectroscopy (MRS) sequence. ASSESSMENT Multiecho MRS scans were performed in four regions of the proximal left femur of each subject, that is, diaphysis, femoral neck, femoral head, and greater trochanter. The examined regions were grouped into red (diaphysis and femoral neck) and yellow marrow regions (femoral head and greater trochanter). STATISTICAL TESTS The Jonckheere-Terpstra test was used to evaluate the impact of increasing disease severity on bone marrow fat fraction (BMFF), marrow conversion index, and fat unsaturation index (UI). Pairwise comparison analysis was performed when a significant trend (P < 0.05) was found. K-means clustering analysis was used to examine the clusters observed when BMFF in the red and yellow regions were studied (diaphysis against greater trochanter). RESULTS BMFF showed a significant decreasing trend with increasing disease severity in both red (TJT = 109.00, z = -4.414, P < 0.05) and yellow marrow regions (TJT = 108.00, z = -4.438, P < 0.05). The opposite trend was observed in UI in both bone marrow regions (red marrow: TJT = 180.5, z = 3.515, P < 0.05; yellow marrow: TJT = 155.0, z = 2.282, P = 0.05). Three distinct forms of marrow adipogenesis were found when plotting BMFF diaphysis against BMFF greater trochanter: 1) normal (centroid: 80.4%, 66.6%), 2) partial disruption (centroid: 51.1%, 16.6%), and 3) total disruption (centroid: 2.6%, 1.6%). DATA CONCLUSION β-thalassemia is associated with decreased marrow fat, and increased marrow fat unsaturation level. LEVEL OF EVIDENCE 2 TECHNICAL EFFICACY STAGE: 3.
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Affiliation(s)
- Umi Nabilah Ismail
- Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Che Ahmad Azlan
- Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Shasha Khairullah
- Haematology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Raja Rizal Azman
- Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Nur Farhayu Omar
- Department of Radiology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia
| | - Mohammad Nazri Md Shah
- Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Chai Hong Yeong
- School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia
| | - Nicholas Jackson
- Red Cell Unit, Department of Haematology, University College Hospital, London, UK
| | - Kwan Hoong Ng
- Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
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Paniz C, Lucena MR, Bertinato JF, Dos Santos MNN, Gomes GW, Figueiredo MS, Sonati MDF, Blaia-D Avila VLN, Green R, Guerra-Shinohara EM. Serum folate and cytokines in heterozygous β-thalassemia. Int J Lab Hematol 2020; 42:718-726. [PMID: 32662566 DOI: 10.1111/ijlh.13287] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Revised: 06/16/2020] [Accepted: 06/18/2020] [Indexed: 01/21/2023]
Abstract
INTRODUCTION Folate deficiency is commonly reported in β-thalassemia. Individuals heterozygous for β-thalassemia may have higher folate requirements than normal individuals. OBJECTIVES To document the concentration of serum total folate and its forms in β-thalassemia heterozygote users (β-TmU) and nonusers (β-TmN) of 5 mg folic acid/d; to determine whether folic acid (FA) consumption from fortified foods allows beta-Tm patients, who do not take FA supplements, to meet their dietary folate requirements; and to investigate the association between higher serum unmetabolized folic acid (UMFA) and inflammatory cytokine concentrations. METHODS Serum total folate and forms were measured in 42 β-Tm (13 β-TmU and 29 β-TmN) and 84 healthy controls. The mononuclear leucocyte mRNA expression of relevant genes and their products and hematological profiles were determined. RESULTS β-TmU had higher serum total folate, 5-methyltetrahydrofolate, UMFA, and tetrahydrofolate (THF) compared with β-TmN. The β-TmN had lower serum total folate and THF than controls. Plasma total homocysteine (tHcy) was lower in β-TmU compared with both β-TmN and controls, while β-TmN had higher tHcy than controls. β-TmU had higher IL-8 than their controls while β-TmN had higher IL-6 and IL-8 than their controls. β-TmU have higher levels of serum total folate, 5- methyltetrahydrofolate, UMFA, and THF than controls. There was no association between UMFA concentrations and cytokine levels. CONCLUSIONS Mandatory flour fortification with FA in Brazil may be insufficient for β-TmN, since they have higher tHcy and lower serum total folate than controls. Furthermore, β-TmN have higher IL-6 levels than β-TmU. UMFA was not associated with inflammatory cytokine levels.
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Affiliation(s)
- Clóvis Paniz
- Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, Brazil.,Departamento de Análises Clínicas e Toxicológicas, Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul, Brazil
| | - Maylla Rodrigues Lucena
- Disciplina de Hematologia e Hemoterapia, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Juliano Felix Bertinato
- Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, Brazil
| | | | - Guilherme Wataru Gomes
- Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, Brazil
| | - Maria Stella Figueiredo
- Disciplina de Hematologia e Hemoterapia, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Maria de Fátima Sonati
- Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade de Campinas, São Paulo, Brazil
| | | | - Ralph Green
- Department of Pathology and Laboratory Medicine, UC Davis School of Medicine, Sacramento, CA, USA
| | - Elvira Maria Guerra-Shinohara
- Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, Brazil.,Disciplina de Hematologia e Hemoterapia, Universidade Federal de São Paulo, São Paulo, Brazil.,Faculdade e Ciências Farmacêuticas, Alimentos e Nutrição, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, Brazil
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Iron status and inherited haemoglobin disorders modify the effects of micronutrient powders on linear growth and morbidity among young Lao children in a double-blind randomised trial. Br J Nutr 2020; 122:895-909. [PMID: 31303184 PMCID: PMC7672373 DOI: 10.1017/s0007114519001715] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Some studies found that providing micronutrient powder (MNP) causes adverse health outcomes, but modifying factors are unknown. We aimed to investigate whether Fe status and inherited Hb disorders (IHbD) modify the impact of MNP on growth and diarrhoea among young Lao children. In a double-blind controlled trial, 1704 children of age 6–23 months were randomised to daily MNP (with 6 mg Fe plus fourteen micronutrients) or placebo for about 36 weeks. IHbD, and baseline and final Hb, Fe status and anthropometrics were assessed. Caregivers provided weekly morbidity reports. At enrolment, 55·6 % were anaemic; only 39·3 % had no sign of clinically significant IHbD. MNP had no overall impact on growth and longitudinal diarrhoea prevalence. Baseline Hb modified the effect of MNP on length-for-age (LAZ) (P for interaction = 0·082). Among children who were initially non-anaemic, the final mean LAZ in the MNP group was slightly lower (–1·93 (95 % CI –1·88, –1·97)) v. placebo (–1·88 (95 % CI –1·83, –1·92)), and the opposite occurred among initially anaemic children (final mean LAZ –1·90 (95 % CI –1·86, –1·94) in MNP v. –1·92 (95 % CI –1·88, –1·96) in placebo). IHbD modified the effect on diarrhoea prevalence (P = 0·095). Among children with IHbD, the MNP group had higher diarrhoea prevalence (1·37 (95 % CI 1·17, 1·59) v. 1·21 (95 % CI 1·04, 1·41)), while it was lower among children without IHbD who received MNP (1·15 (95 % CI 0·95, 1·39) v. 1·37 (95 % CI 1·13, 1·64)). In conclusion, there was a small adverse effect of MNP on growth among non-anaemic children and on diarrhoea prevalence among children with IHbD.
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Osman HA, Hamid MMA, Ahmad RB, Saleem M, Abdallah SA. Prevalence of 3.7 and 4.2 deletions in Sudanese patients with red cells hypochromia and microcytosis. BMC Res Notes 2020; 13:65. [PMID: 32041645 PMCID: PMC7011266 DOI: 10.1186/s13104-020-4933-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Accepted: 02/01/2020] [Indexed: 12/03/2022] Open
Abstract
Objective Alpha-thalassemia is a genetic disorder characterized by deletions of one or more α globin genes that result in deficient of α globin chains reducing haemoglobin concentration. The study aimed to screen 97 patients with microcytosis and hypochromasia for the 3.7 and 4.2 alpha thalassemia deletion mutations. Results Out of 97 patients screened, only 7 were carriers for the 3.7 deletion and all patients were negative for the 4.2 deletion. The 3.7 deletion was found in Foor, Hawsa and Rezagat Sudanese tribes. In the carriers of the 3.7 deletion, Red Blood Cells and Haematocrit were significantly increased. The Red Blood Cells were 7.23 ± 0.78 × 1012/L in adult males and 7.21 ± 0.67 × 1012/L in adult females while in children were 5.07 ± 0.87 × 1012/L. The mean cell volume and mean cell haemoglobin were significantly decreased, but the mean cell haemoglobin concentration slightly decreased. Haemoglobin levels didn’t revealed statistically significant decrease in adult males (11.7 ± 0.57 g/dL) and adult females (11.25 ± 0.64 g/dL), while in children were (11.6 ± 2.95 g/dL). Haemoglobin electrophoresis revealed two patients of the 3.7 and 4.2 negative were carriers for β-thalassemia. The study concluded that α3.7 deletion has frequency of 0.07 in Sudanese with hypochromasia and microcytosis.
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Affiliation(s)
- Hussam Ali Osman
- Department of Biotechnology, School of Pharmacy, Ahafad University for Women, Omdurman, Sudan.
| | | | - Rahimah Binti Ahmad
- Hematology Unit, Cancer Research Centre Institute for Medical Research Jalan Pahang, 50588, Kuala Lumpur, Malaysia
| | - Mohamed Saleem
- Advanced Genomics SDN BHD (GenomixLAB), Kota Damansara, Malaysia
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Diana A, Purnamasari DM, Rahmannia S, Luftimas DE, Haszard JJ, Gibson RS, Houghton LA. Multimicronutrient Biomarkers Are Related to Anemia during Infancy in Indonesia: A Repeated Cross-Sectional Study. Curr Dev Nutr 2019; 3:nzz022. [PMID: 31037278 PMCID: PMC6483051 DOI: 10.1093/cdn/nzz022] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Revised: 03/20/2019] [Accepted: 03/28/2019] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Anemia during infancy in Indonesia is common, with iron deficiency (ID) assumed to be the major cause. Other micronutrients besides iron may have a role in determining hemoglobin (Hb) but have not yet been explored in Indonesia. OBJECTIVE We investigated 7 micronutrient biomarkers and selected nonnutritional factors as potential predictors of Hb and anemia at ages 6, 9, and 12 mo in a cohort of Indonesian infants at risk of coexisting micronutrient deficiencies. METHODS Apparently healthy breastfed infants were randomly selected from birth registries at 6 mo (n = 230) and followed-up at 9 mo (n = 202) and 12 mo (n = 190). Hb, serum micronutrient biomarkers-iron [as ferritin and serum soluble transferrin receptor (sTfR)], zinc, selenium, folate, vitamin A [as retinol-binding protein (RBP)], vitamin B-12, and vitamin D (as 25-hydroxyvitamin D) (adjusted for inflammation, where appropriate)-and maternal sociodemographic status, health, BMI, heminthiasis, and selected Hb genetic disorders were measured. Multivariate analysis examined relations between micronutrient biomarkers and nonnutritional factors (except helminthiasis and genetic Hb disorders) with Hb and anemia at 6 and 12 mo. RESULTS ID (based on ferritin) was a predictor of lower Hb and anemia at both 6 and 12 mo of age (P < 0.02). Additional predictors at 6 mo were tertiary education and higher maternal Hb for higher Hb, sex (being male) and inflammation (P < 0.05) for both lower Hb and anemia, and greater maternal height (P = 0.036) for anemia only. At 12 mo, a significant biomarker predictor besides ID was RBP (P = 0.035) for Hb. CONCLUSION ID was a major contributor to lower Hb and anemia, although RBP was also associated.
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Affiliation(s)
- Aly Diana
- Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
- Department of Human Nutrition, University of Otago, Dunedin, New Zealand
| | | | - Sofa Rahmannia
- Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
| | - Dimas E Luftimas
- Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
| | - Jillian J Haszard
- Department of Human Nutrition, University of Otago, Dunedin, New Zealand
| | - Rosalind S Gibson
- Department of Human Nutrition, University of Otago, Dunedin, New Zealand
| | - Lisa A Houghton
- Department of Human Nutrition, University of Otago, Dunedin, New Zealand
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11
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Byrd KA, Williams TN, Lin A, Pickering AJ, Arnold BF, Arnold CD, Kiprotich M, Dentz HN, Njenga SM, Rao G, Colford JM, Null C, Stewart CP. Sickle Cell and α+-Thalassemia Traits Influence the Association between Ferritin and Hepcidin in Rural Kenyan Children Aged 14-26 Months. J Nutr 2018; 148:1903-1910. [PMID: 30517728 PMCID: PMC6669948 DOI: 10.1093/jn/nxy229] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Revised: 05/23/2018] [Accepted: 08/16/2018] [Indexed: 01/01/2023] Open
Abstract
Background The relation between subclinical hemoglobinopathies and concentrations of the iron-regulatory hormone hepcidin is not well characterized. Objective We investigated the relation of hepcidin concentration with hemoglobinopathies among young children in Kenya. Methods We quantified serum hepcidin and ferritin in 435 Kenyan children aged 14-20 mo in a subsample of the Water, Sanitation, and Handwashing (WASH) Benefits Trial. Blood samples were genotyped for α+-thalassemia and for sickle cell disorder. Hepcidin was compared across sickle cell and α+-thalassemia genotypes separately by using generalized linear models, and children who were normozygous for both conditions were also compared with those who had either of these conditions. In the association between hepcidin and ferritin, we assessed effect modification by genotype. Results In this population, we found that 16.2% had sickle cell trait and 0.2% had sickle cell disorder, whereas 40.0% were heterozygous for α+-thalassemia and 8.2% were homozygous. Hepcidin concentration did not differ by genotype, but effect modification was found by genotype in the association between hepcidin and ferritin (P < 0.1). Among normozygous sickle cell children (HbAA), there was an association between hepcidin and ferritin (β = 0.92; 95% CI: 0.72, 1.10). However, among those with sickle cell trait (HbAS), the association was no longer significant (β = 0.31; 95% CI: -0.04, 0.66). Similarly, among children who were normozygous (αα/αα) or heterozygous (-α/αα) for α+-thalassemia, hepcidin and ferritin were significantly associated [β = 0.94 (95% CI: 0.68, 1.20) and β = 0.77 (95% CI: 0.51, 1.03), respectively]; however, in children who were homozygous for α+-thalassemia (-α/-α), there was no longer a significant association (β = 0.45; 95% CI: -0.10, 1.00). Conclusion Hepcidin was not associated with hemoglobin genotype, but there may be a difference in the way hepcidin responds to iron status among those with either sickle cell trait or homozygous α+-thalassemia in young Kenyan children. This trial was registered at clinicaltrials.gov as NCT01704105.
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Affiliation(s)
- Kendra A Byrd
- Department of Nutrition, University of California, Davis, Davis, CA
| | - Thomas N Williams
- Imperial College, St. Mary's Hospital, London, United Kingdom
- Kenya Medical Research Institute (KEMRI)/Wellcome Trust Research Program, Kilifi, Kenya
| | - Audrie Lin
- Division of Epidemiology and Biostatistics, School of Public Health, University of California, Berkeley, Berkeley, CA
| | - Amy J Pickering
- Department of Civil and Environmental Engineering, Tufts University, Medford, MA
| | - Benjamin F Arnold
- Division of Epidemiology and Biostatistics, School of Public Health, University of California, Berkeley, Berkeley, CA
| | - Charles D Arnold
- Department of Nutrition, University of California, Davis, Davis, CA
| | | | - Holly N Dentz
- Department of Nutrition, University of California, Davis, Davis, CA
- Innovations for Poverty Action, Nairobi, Kenya
| | | | | | - John M Colford
- Division of Epidemiology and Biostatistics, School of Public Health, University of California, Berkeley, Berkeley, CA
| | - Clair Null
- Mathematica Policy Research, Washington, DC
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12
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Oikonomidou PR, Rivella S. What can we learn from ineffective erythropoiesis in thalassemia? Blood Rev 2018; 32:130-143. [PMID: 29054350 PMCID: PMC5882559 DOI: 10.1016/j.blre.2017.10.001] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2016] [Revised: 09/30/2017] [Accepted: 10/02/2017] [Indexed: 02/07/2023]
Abstract
Erythropoiesis is a dynamic process regulated at multiple levels to balance proliferation, differentiation and survival of erythroid progenitors. Ineffective erythropoiesis is a key feature of various diseases, including β-thalassemia. The pathogenic mechanisms leading to ineffective erythropoiesis are complex and still not fully understood. Altered survival and decreased differentiation of erythroid progenitors are both critical processes contributing to reduced production of mature red blood cells. Recent studies have identified novel important players and provided major advances in the development of targeted therapeutic approaches. In this review, β-thalassemia is used as a paradigmatic example to describe our current knowledge on the mechanisms leading to ineffective erythropoiesis and novel treatments that may have the potential to improve the clinical phenotype of associated diseases in the future.
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Affiliation(s)
- Paraskevi Rea Oikonomidou
- Department of Pediatrics, Division of Hematology, Children's Hospital of Philadelphia (CHOP), Philadelphia, PA, USA.
| | - Stefano Rivella
- Department of Pediatrics, Division of Hematology, Children's Hospital of Philadelphia (CHOP), Philadelphia, PA, USA; Cell and Molecular Biology Graduate Group (CAMB), University of Pennsylvania, Philadelphia, PA, USA.
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13
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Mojzikova R, Koralkova P, Holub D, Saxova Z, Pospisilova D, Prochazkova D, Dzubak P, Horvathova M, Divoky V. Two novel mutations (p.(Ser160Pro) and p.(Arg472Cys)) causing glucose-6-phosphate isomerase deficiency are associated with erythroid dysplasia and inappropriately suppressed hepcidin. Blood Cells Mol Dis 2018; 69:23-29. [DOI: 10.1016/j.bcmd.2017.04.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2017] [Revised: 04/12/2017] [Accepted: 04/13/2017] [Indexed: 01/25/2023]
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14
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Bahizire E, Tugirimana PL, Dramaix M, Zozo D, Bahati M, Mwale A, Meuris S, Donnen P. Malaria Is More Prevalent Than Iron Deficiency among Anemic Pregnant Women at the First Antenatal Visit in Rural South Kivu. Am J Trop Med Hyg 2017; 97:1551-1560. [PMID: 29016317 DOI: 10.4269/ajtmh.17-0267] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
Anemia is common during pregnancy and is associated with poor outcomes. Objectives were not only 1) to determine the prevalence of anemia and iron deficiency (ID) but also 2) to identify other factors associated with anemia in pregnant women from South Kivu province, in the eastern Democratic Republic of Congo. Between December 2013 and March 2014, 531 women attending the first antenatal visit in their second trimester of pregnancy were recruited. Sociodemographic, clinical, and biological data were collected. Hemoglobin (Hb) was determined by a portable photometer (Hemocue® Hb201+), and anemia was defined as altitude-adjusted Hb < 110 g/L. ID was defined as serum ferritin < 15 μg/L adjusted for inflammation status (C-reactive protein [CRP] > 5 mg/L and/or α-1-acid glycoprotein > 1 g/L) whereas hypoalbuminemia was defined as serum albumin < 35 g/L. A Giemsa-stained blood smear was used to diagnose malaria. The median age (interquartile range ) was 25.5 (21.1-31.3) years, with anemia in 17.6% and ID in 8%. Malaria was present in 7.5% and hypoalbuminemia among 44%. Soluble transferrin receptor concentration was higher in the presence of inflammation and/or malaria. In the final logistic regression model, factors independently associated with anemia were malaria (adjusted odds ratio [aOR]: 11.24 (4.98-25.37) P < 0.001), hypoalbuminemia [aOR: 2.14 (1.27-3.59); P = 0.004] and elevated CRP [aOR: 1.94 (1.10-3.45); P = 0.022]. ID was not highly prevalent and not associated with anemia in our population. Effective control of anemia during pregnancy in this region should consider fighting malaria and other infectious diseases in combination with measures to improve women's nutrition, both before and during pregnancy.
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Affiliation(s)
- Esto Bahizire
- Center of Research in Epidemiology, Biostatistics and Clinical Research, Université Libre de Bruxelles, Brussels, Belgium.,Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya.,Centre de Recherche en Sciences Naturelles de Lwiro, Bukavu, DR Congo
| | - P Lundimu Tugirimana
- Faculty of Medicine, Université de Goma, Goma, DR Congo.,Department of Clinical Biology, National University of Rwanda, Kigali, Rwanda
| | - Michèle Dramaix
- Center of Research in Epidemiology, Biostatistics and Clinical Research, Université Libre de Bruxelles, Brussels, Belgium
| | - Déogratias Zozo
- Centre de Recherche en Sciences Naturelles de Lwiro, Bukavu, DR Congo
| | - Mugisho Bahati
- Division Provinciale de la Santé du Sud-Kivu, Bukavu, DR Congo
| | - Andrew Mwale
- Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya
| | - Sylvain Meuris
- Laboratory of experimental hormonology, Université Libre de Bruxelles, Brussels, Belgium
| | - Philippe Donnen
- Center of Research in Health Policy and Systems-International Health, Université Libre de Bruxelles, Brussels, Belgium
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15
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Mathew R, Huang J, Wu JM, Fallon JT, Gewitz MH. Hematological disorders and pulmonary hypertension. World J Cardiol 2016; 8:703-718. [PMID: 28070238 PMCID: PMC5183970 DOI: 10.4330/wjc.v8.i12.703] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Revised: 09/07/2016] [Accepted: 10/09/2016] [Indexed: 02/06/2023] Open
Abstract
Pulmonary hypertension (PH), a serious disorder with a high morbidity and mortality rate, is known to occur in a number of unrelated systemic diseases. Several hematological disorders such as sickle cell disease, thalassemia and myeloproliferative diseases develop PH which worsens the prognosis. Associated oxidant injury and vascular inflammation cause endothelial damage and dysfunction. Pulmonary vascular endothelial damage/dysfunction is an early event in PH resulting in the loss of vascular reactivity, activation of proliferative and antiapoptotic pathways leading to vascular remodeling, elevated pulmonary artery pressure, right ventricular hypertrophy and premature death. Hemolysis observed in hematological disorders leads to free hemoglobin which rapidly scavenges nitric oxide (NO), limiting its bioavailability, and leading to endothelial dysfunction. In addition, hemolysis releases arginase into the circulation which converts L-arginine to ornithine, thus bypassing NO production. Furthermore, treatments for hematological disorders such as immunosuppressive therapy, splenectomy, bone marrow transplantation, and radiation have been shown to contribute to the development of PH. Recent studies have shown deregulated iron homeostasis in patients with cardiopulmonary diseases including pulmonary arterial hypertension (PAH). Several studies have reported low iron levels in patients with idiopathic PAH, and iron deficiency is an important risk factor. This article reviews PH associated with hematological disorders and its mechanism; and iron homeostasis and its relevance to PH.
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16
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Leecharoenkiat K, Lithanatudom P, Sornjai W, Smith DR. Iron dysregulation in beta-thalassemia. ASIAN PAC J TROP MED 2016; 9:1035-1043. [PMID: 27890361 DOI: 10.1016/j.apjtm.2016.07.035] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2016] [Revised: 08/01/2016] [Accepted: 10/14/2016] [Indexed: 11/24/2022] Open
Abstract
Iron deficiency anemia and iron overload conditions affect more than one billion people worldwide. Iron homeostasis involves the regulation of cells that export iron into the plasma and cells that utilize or store iron. The cellular iron balance in humans is primarily mediated by the hepcidin-ferroportin axis. Ferroportin is the sole cellular iron export protein, and its expression is regulated transcriptionally, post-transcriptionally and post-translationally. Hepcidin, a hormone produced by liver cells, post-translationally regulates ferroportin expression on iron exporting cells by binding with ferroportin and promoting its internalization by endocytosis and subsequent degradation by lysosomes. Dysregulation of iron homeostasis leading to iron deposition in vital organs is the main cause of death in beta-thalassemia patients. Beta-thalassemia patients show marked hepcidin suppression, ineffective erythropoiesis, anemia and iron overload. Beta-thalassemia is common in the Mediterranean region, Southeast Asia and the Indian subcontinent, and the focus of this review is to provide an update on the factors mediating hepcidin related iron dysregulation in beta-thalassemia disease. Understanding this process may pave the way for new treatments to ameliorate iron overloading and improve the long term prognosis of these patients.
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Affiliation(s)
- Kamonlak Leecharoenkiat
- Department of Clinical Microscopy, Faculty of Allied Health Sciences, Chulalongkorn University, 154 Rama 4 Road, Bangkok 10330, Thailand
| | - Pathrapol Lithanatudom
- Department of Biology, Faculty of Science, Chiang Mai University, 239 Huaykaew Road, Amphur Muang, Chiang Mai 50200, Thailand
| | - Wannapa Sornjai
- Molecular Pathology Laboratory, Institute of Molecular Biosciences, Mahidol University, 25/25 Phuttamonthon 4 Road, Salaya, Nakhon Pathom 73170, Thailand
| | - Duncan R Smith
- Molecular Pathology Laboratory, Institute of Molecular Biosciences, Mahidol University, 25/25 Phuttamonthon 4 Road, Salaya, Nakhon Pathom 73170, Thailand.
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17
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Ribeiro S, Garrido P, Fernandes J, Rocha S, Rocha-Pereira P, Costa E, Belo L, Reis F, Santos-Silva A. Recombinant human erythropoietin-induced erythropoiesis regulates hepcidin expression over iron status in the rat. Blood Cells Mol Dis 2016; 59:63-70. [DOI: 10.1016/j.bcmd.2016.04.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2016] [Revised: 04/13/2016] [Accepted: 04/13/2016] [Indexed: 12/21/2022]
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18
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Camaschella C, Nai A. Ineffective erythropoiesis and regulation of iron status in iron loading anaemias. Br J Haematol 2015; 172:512-23. [PMID: 26491866 DOI: 10.1111/bjh.13820] [Citation(s) in RCA: 119] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The definition 'iron loading anaemias' encompasses a group of inherited and acquired anaemias characterized by ineffective erythropoiesis, low hepcidin levels, excessive iron absorption and secondary iron overload. Non-transfusion-dependent β-thalassaemia is the paradigmatic example of these conditions that include dyserythropoietic and sideroblastic anaemias and some forms of myelodysplasia. Interrupting the vicious cycle between ineffective erythropoiesis and iron overload may be of therapeutic benefit in all these diseases. Induction of iron restriction by means of transferrin infusions, minihepcidins or manipulation of the hepcidin pathway prevents iron overload, redistributes iron from parenchymal cells to macrophage stores and partially controls anaemia in β-thalassaemic mice. Inhibition of ineffective erythropoiesis by activin ligand traps improves anaemia and iron overload in the same models. Targeting iron loading or ineffective erythropoiesis shows promise in preclinical studies; activin ligand traps are in clinical trials with promising results and may be useful in patients with ineffective erythropoiesis.
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Affiliation(s)
- Clara Camaschella
- Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Vita Salute University, Milano, Italy
| | - Antonella Nai
- Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Vita Salute University, Milano, Italy
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19
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Hepcidin is suppressed by erythropoiesis in hemoglobin E β-thalassemia and β-thalassemia trait. Blood 2014; 125:873-80. [PMID: 25519750 DOI: 10.1182/blood-2014-10-606491] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Hemoglobin E (HbE) β-thalassemia is the most common severe thalassemia syndrome across Asia, and millions of people are carriers. Clinical heterogeneity in HbE β-thalassemia is incompletely explained by genotype, and the interaction of phenotypic variation with hepcidin is unknown. The effect of thalassemia carriage on hepcidin is also unknown, but it could be relevant for iron supplementation programs aimed at combating anemia. In 62 of 69 Sri Lankan patients with HbE β-thalassemia with moderate or severe phenotype, hepcidin was suppressed, and overall hepcidin inversely correlated with iron accumulation. On segregating by phenotype, there were no differences in hepcidin, erythropoiesis, or hemoglobin between severe or moderate disease, but multiple linear regression showed that erythropoiesis inversely correlated with hepcidin only in severe phenotypes. In moderate disease, no independent predictors of hepcidin were identifiable; nevertheless, the low hepcidin levels indicate a significant risk for iron overload. In a population survey of Sri Lankan schoolchildren, β-thalassemia (but not HbE) trait was associated with increased erythropoiesis and mildly suppressed hepcidin, suggesting an enhanced propensity to accumulate iron. In summary, the influence of erythropoiesis on hepcidin suppression associates with phenotypic disease variation and pathogenesis in HbE β-thalassemia and indicates that the epidemiology of β-thalassemia trait requires consideration when planning public health iron interventions.
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