Challenges of blood transfusions in β-thalassemia

Shah, Farrukh; Sayani, Farzana; Trompeter, Sara; Drašar, Emma; Piga, Antonio

doi:10.1016/j.blre.2019.100588

Cited by 160 publications

(150 citation statements)

References 103 publications

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“…Possible reasons for this are the lack of altruistic voluntary blood donors and the inadequate testing of blood donations for HCV. Many blood transfusion centers and hospitals have inadequate resources and kits for screening blood donations [5]. The root cause of the high prevalence is predominantly the lack of adequate regulation of blood banks and monitoring to assess compliance with transfusion safety standards.…”

Section: Discussionmentioning

confidence: 99%

“…Around 1.5% (80-90 million people) of the worldwide population are carriers for β-thalassemia, with 50,000-60,000 new β-thalassemia cases being born each year [2]. β-thalassemia is most prevalent in the populations of Asia, the Indian subcontinent, the Mediterranean countries, Africa and the Middle East [3][4][5]. In Pakistan, β-thalassemia is one of the commonest inherited disorders, with a carrier frequency of 5 to 7% of the Pakistani population [2].…”

Section: Introductionmentioning

confidence: 99%

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The prevalence of hepatitis C virus infection in β-thalassemia patients in Pakistan: a systematic review and meta-analysis

2020

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Background: Hepatitis C virus infection is the most commonly reported bloodborne infection in Pakistan. Frequent blood transfusions in β-thalassemia patients expose them to a high risk of HCV infection. The purpose of this paper is to summarise the current data on the prevalence of HCV infection in β-thalassemia patients in Pakistan by using a systematic review and meta-analysis. Methods: PubMed, EMBASE, Web of Sciences, the Cochrane Library, Directory of Open Access Journal and local databases were systematically searched for studies published between January 1st, 1995 and May 31st, 2019. Metaanalysis was performed using the DerSimonian and Laird random-effects models with inverse variance weighting. The presence of publication bias was tested by Egger test, and the methodological quality of each included article was evaluated by the STROBE. Results: We identified a total of 229 potential studies, of which 27 studies were finally considered in the metaanalysis. The pooled prevalence of HCV in β-thalassemia patients in Pakistan was 36.21% (95% CI: 28.98-43.75%) based on 5789 β-thalassemia patients, but there was considerable heterogeneity. Meta-analysis estimated the HCV prevalence among the β-thalassemia patients at 45.98% (95% CI: 38.15-53.90%) in Punjab, 31.81% (95% CI: 20.27-44.59%) in Sindh, and 28.04% (95% CI: 13.58-45.26%) in Khyber Pakhtunkhwa. Meta-regression analysis showed that geographical location was a key source of heterogeneity. Conclusions: The pooled prevalence of HCV in β-thalassemia patients in Pakistan was more than one in three, and higher than in neighbouring countries. It varies regionally within the country. With the use of standard prevention procedures during blood transfusion, the risk of HCV transmission in β-thalassemia patients could be controlled and the prevalence of HCV in β-thalassemia patients reduced.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The prevalence of hepatitis C virus infection in β-thalassemia patients in Pakistan: a systematic review and meta-analysis

2020

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“…β-thalassemia (β-thal), one of the most common genetic diseases worldwide, is caused by over 200 different types of mutations in the β-globin (HBB) gene [1]. Normally, HBB pairs with α-globin (HBA) in a one-to-one ratio to form the tetrameric hemoglobin molecule, and with the insu cient production of HBB, unpaired α-globin chains precipitate, thereby causing toxic death to the developing erythrocyte or erythrocyte precursor and leading to the insu cient formation of mature red blood cells (RBCs) [2]. Ineffective erythropoiesis leads to anemia, and severe anemia can cause a high level of mortality or shortened life expectancy if left untreated.…”

Section: Introductionmentioning

confidence: 99%

A Universal Approach to Target Various HBB Gene Mutations in Hematopoietic Stem/Progenitor Cells for Beta-Thalassemia Gene Therapy by CRISPR/Cas9 and the rAAV6 Vector

Yang

Cheng

et al. 2020

Preprint

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Background Engineered nuclease-mediated gene targeting through homology-directed repair (HDR) in autologous hematopoietic stem and progenitor cells (HSPCs) has the potential to cure β-thalassemia (β-thal). Although previous studies have precisely corrected site-specific HBB mutations by HDR in vitro and in vivo, targeting the various HBB mutations in β-thal is still challenging. Here, we devised a universal strategy to achieve repaired most types of HBB mutations through the CRISPR/Cas9 and the rAAV6 donor. Methods Using cord blood-derived HSPCs from health donors, we tested the strategy to achieved highly efficient targeted integration by optimizing design and delivery parameters of a ribonucleoprotein (RNP) complex comprising Cas9 protein and modified single guide RNA, together with a rAAV6 donor. We assessed the edited HSPCs function in vitro by methylcellulose colonies assay, CFU assay, differentiation experiment and Wright-Giemsa staining. Edited HSPCs transplanted into NSI mice to assess the long-term reconstitution in vivo. Whole-genome sequencing was used to analysis the off-target mutagenesis of edited HSPCs. Results Edited HSPCs exhibited normal multilineage formation and erythroid differentiation abilities without off-target mutagenesis and retained the ability to engraft. Moreover, we used the strategy to efficiently correct the β-CD41/42 mutation of patient-derived HSPCs, erythrocytes differentiation from which expressed more HBB mRNA than uncorrected cells. Conclusion This strategy demonstrated a universal approach to correct most types of HBB gene mutations in β-thal.

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“…2 In addition to genetic factors, the iron overload might be affected by basic thalassemia therapy including polytransfusion treatment and its accompanied chelation therapy. 3 Those factors have be controlled and recognized before conclusion of the effect of the HFE polymorphisms. Nevertheless, if we focus on HFE polymorphism as a single factor regardless other possible confounding factors, the basic molecular change due to each HFE polymorphism can well explain the observation by Sharif et al 1 Based on the quantum molecular weight calculation as presented in the previous referencing publications, 4,5 the molecular weight changes HFE H63D and C282Y are <22 and +60 g/Mol, respectively.…”

Section: To the Editormentioning

confidence: 99%

Comment on: Hemochromatosis (HFE) gene mutations (H63D and C282Y) and iron overload in beta-thalassemia major

Yasri

Wiwanitkit²

2019

SMJ

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Challenges of blood transfusions in β-thalassemia

Cited by 160 publications

References 103 publications

The prevalence of hepatitis C virus infection in β-thalassemia patients in Pakistan: a systematic review and meta-analysis

The prevalence of hepatitis C virus infection in β-thalassemia patients in Pakistan: a systematic review and meta-analysis

A Universal Approach to Target Various HBB Gene Mutations in Hematopoietic Stem/Progenitor Cells for Beta-Thalassemia Gene Therapy by CRISPR/Cas9 and the rAAV6 Vector

Comment on: Hemochromatosis (HFE) gene mutations (H63D and C282Y) and iron overload in beta-thalassemia major

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