bims-conane 2024-06-30 papers

Issue of 2024‒06‒30
nine papers selected by
João Conrado Khouri dos Santos, University of São Paulo

Lancet Haematol. 2024 Jul;pii: S2352-3026(24)00183-2. [Epub ahead of print]11(7): e483

Obiageli Nnodu: sickle cell disease in Africa's largest nation.

DOI: https://doi.org/10.1016/S2352-3026(24)00183-2

Int J Mol Sci. 2024 Jun 07. pii: 6317. [Epub ahead of print]25(12):

Genetic Modifiers of Stroke in Patients with Sickle Cell Disease-A Scoping Review.

International Hemoglobinopathy Research Network (INHERENT)

Sickle cell disease (SCD) clinically manifests itself with a myriad of complications. Stroke, both ischemic and hemorrhagic, as well as silent white matter changes, occurs at a relatively high prevalence. Understanding why and in whom stroke is most likely to occur is critical to the effective prevention and treatment of individuals with SCD. Genetic studies, including genome- and exome-wide association studies (GWAS and EWAS), have found several key modifiers associated with increased stroke/stroke risk in SCD via mechanisms including Hemoglobin F (HbF) modulation, inflammation, cellular adhesion, endothelial disruption, and hemolysis. We present a review on the modifiers that have most clearly demonstrated an association to date. More studies are needed to validate other potential polymorphisms and identify new ones. Incorporating gene-focused screenings in clinical care could provide avenues for more targeted, more effective, and less toxic prevention of stroke in this population. The data from this review will be used to inform the initial GWAS performed by the International Hemoglobinopathy Research Network (INHERENT) consortium.

Keywords: cerebral vasculopathy; genetic modifiers; sickle cell disease; stroke

DOI: https://doi.org/10.3390/ijms25126317

Hemasphere. 2024 Jun;8(6): e107

Correction to "New approaches in gene therapy for sickle cell disease, moving in vivo".

[This corrects the article DOI: 10.1002/hem3.43.].

DOI: https://doi.org/10.1002/hem3.107

Transfusion. 2024 Jun 27.

Therapeutic plasma exchange for sickle cell disease acute complications: A systematic review.

Romario B Denoon, Alexandre Soares Ferreira Junior, Brandi Tuttle, Oluwatoyosi A Onwuemene.

Keywords: blood component removal; multiorgan failure; red blood cell exchange; sickle cell disease; therapeutic apheresis; therapeutic plasma exchange

DOI: https://doi.org/10.1111/trf.17932

Br J Haematol. 2024 Jun 23.

Seeing haemoglobin SC: Challenging the misperceptions.

Catherine Segbefia, Lori Luchtman-Jones.

Historically understudied and regarded as a mild type of sickle cell disease, HbSC can be associated with significant, progressive complications. Prospective studies are urgently needed to address treatment gaps for HbSC disease. Commentary on: Nelson et al. The clinical spectrum of HbSC sickle cell disease-not a benign condition. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19523.

Keywords: HbC gene; HbSC; sickle cell disease

DOI: https://doi.org/10.1111/bjh.19580

Front Biosci (Schol Ed). 2024 Jun 12. 16(2): 11

Genotyping the BCL11A Single Nucleotide Polymorphism and Associated Levels of Fetal Hemoglobin in Mauritanian Sickle Cell Patients.

Aminetou Taleb Brahim, Mariem Taleb, Harouna Soumaré, Sidi Mohamed Ghaber, Aminetou Mohamed, Ali Ould Mohamed Salem Boukhary.

BACKGROUND: Sickle cell disease (SCD) is a major heritable genetic disease in sub-Saharan Africa, including Mauritania. Fetal hemoglobin (HbF) can affect the pathophysiology, moderate the clinical course, and offer prospects for curative treatment of SCD. This study aimed to investigate the influence of single nucleotide polymorphisms (SNPs) in the BCL11A gene on the levels of HbF and hematological parameters in Mauritanian sickle cell (HbSS) patients.METHODS: Complete blood count was assessed in 565 patients suspected to have SCD. Polymerase chain reaction (PCR)-restriction fragment length polymorphism was performed to identify the HbSS, and sequencing was used for genotyping three SNPs: rs4671393 (A>G) and rs11886868 (C>T) in the intron 2 and rs1052520 (G>A) in the 3'UTR regions of the BCL11A gene in 50 sickle cell patients.
RESULTS: The prevalence of HbSS among the study population was 8.8% (50/565), and the mean (± standard deviation) of HbF level was 15.0% (± 6.0%). Sequencing showed the presence of three genotypes: AA (13.6%), AG (46.6%), GG (39.6%) in rs4671393; CC (17.6%), CT (48.7%), and TT (33.6%) in rs11886868. All samples from HbSS individuals displayed a wild-type genotype in the rs1052520 allele. The prevalence of minor alleles A (rs4671393) and C (rs11886868) were 37% and 39%, respectively. There was a statistically significant association (p = 0.034) between rs4671393 SNP and elevated HbF (mean 12.72 ± 6.26%).
CONCLUSIONS: The study of three SNPs in the BCL11A locus in Mauritanian patients with SCD showed a significant association of rs4671393 allele with the HbF level. Further research is needed to explore additional SNPs in the BCL11A locus and investigate other genetic markers reported to modulate HbF levels, such as HBS1L-MYB and Xmn1-HBG2, to improve the management of this potentially life-threatening condition in Mauritania.

Keywords: BCL11A gene; Mauritania; fetal hemoglobin; sickle cell disease; single nucleotide polymorphisms

DOI: https://doi.org/10.31083/j.fbs1602011

PLoS One. 2024 ;19(6): e0306194

Molecular characterization of HAMP rs10421768 gene and phenotypic expression of hepcidin; a case-control study among sickle cell anaemia patients in Ghana.

Samuel Kwasi Appiah, Charles Nkansah, Gabriel Abbam, Felix Osei-Boakye, Kofi Mensah, Simon Bannison Bani, Solomon Chemogo, Lydia Sarpong, Takyi Godfred Addae, Daniel Boamah Sefa, Richard Adu Croffien, Larry Adom, Rekhiatu Oboirien Abdul Rauf, Farrid Boadu, Godfred Appiah Amoah, Ejike Felix Chukwurah.

BACKGROUND: The sporadic nature of blood transfusion therapy coupled with the alteration of HAMP genes may exacerbate the risk of iron burden in sickle cell anaemia (SCA) patients. The study determined the polymorphic distribution of the HAMP promoter gene rs10421768 and hepcidin levels in SCA patients.METHOD: Sixty participants aged ≥12years [45 SCA patients and 15 controls (HbA)] were recruited from 15th March, 2023 to 20th July, 2023 for a case-control study at Methodist Hospital Wenchi, Ghana. Complete blood count and hepcidin levels assessment were done using haematology analyzer and ELISA, respectively. Genomic DNA was extracted using the Qiagen Kit, and HAMP gene rs10421768 (c.-582 A>G) was sequenced using the MassARRAY method. Data were analysed using SPSS version 26.0.
RESULTS: The frequencies of the HAMP promoter rs10421768 genotypes AA, AG, and GG were 64.4%, 33.3%, and 2.2% in SCA patients, and 86.7%, 13.3%, and 0% in the controls, respectively. Serum hepcidin levels were significantly higher among controls than cases [204.0 (154.1-219.3) vs 150.2 (108.1-195.6)μg/L, p<0.010]. Participants with HAMP rs10421768 homozygous A genotype had higher serum levels of hepcidin compared with those in the wild genotypes (AG/GG) group [(188.7 (130.9-226.9) vs 136.8 (109.7-157.8)μg/L, p<0.016]. Disease severity and blood cell parameters were not associated with the HAMP variants (p>0.05).
CONCLUSION: The HAMP promoter rs10421768 AA genotype has the highest frequency of distribution and the GG genotype with the least distribution. Participants with HAMP rs10421768 G allele (c.-582A>G) had reduced levels of hepcidin. HAMP rs10421768 genotypes had no association with blood cell parameters and disease severity. The HAMP rs10421768 genotypes may influence serum levels of hepcidin. Further study is required to elucidate the potential effect of the G allele on hepcidin transcription.

DOI: https://doi.org/10.1371/journal.pone.0306194

Cureus. 2024 May;16(5): e61185

Hospitalization Events Among Adolescents and Adults With Sickle Cell Disease in a Tertiary Care Center in Central India.

Preetam Wasnik, Pranita Das, Ajit Kumar, Pankaj K Kannauje, Rohini R, Vinay Pandit, Tarun Sahu, Jyoti Sahu.

BACKGROUND: Sickle cell disease (SCD) is an inherited red blood cell disorder, wherein mutation causes the substitution of glutamic acid to valine at the sixth position of the β-globin chain. These include sickle cell anemia (homozygous sickle mutation), sickle-beta thalassemia, and hemoglobin SCD. The clinical manifestations of SCD are protean. Individuals with SCD suffer from both acute and chronic complications, which include recurring episodes of pain commonly called vaso-occlusive crisis (VOC) - acute chest syndrome (ACS); aseptic necrosis of the bone; micro-infarction of the spleen, brain, and kidney; infections; stroke; and organ damage affecting every part of the body. SCD necessitates frequent hospitalizations because of severe complications, which pose a significant burden on caregivers and economic strain on healthcare systems. The pattern of hospital admission with SCD varies in different parts of the world.OBJECTIVE: This study aimed to determine the causes of hospitalization among adolescent and adult patients with SCD and to determine factors associated with their hospital stay.
METHODS: The study was a hospital-based prospective observational study comprising adolescent and adult patients diagnosed with SCD, aged 15-45 years, who were hospitalized in the Department of General Medicine at All India Institute of Medical Sciences in Raipur from August 2021 to August 2022.
RESULT: According to our study, the primary reason for hospitalization was a painful crisis, accounting for 63% of cases, followed by infection (17%), ACS (11%), and acute hemolytic crisis (9%). Notably, we did not observe any significant differences between genders and causes of admission (p > 0.05). Joint pain (p = 0.005), back pain (p = 0.001), and chest pain (p = 0.001) were more frequently reported by adults over the age of 19. In addition, our analysis of the duration of hospital stays and various factors revealed that patients admitted for infections had a significantly longer mean hospital stay duration (p = 0.040).
CONCLUSION: Acute painful crises were the primary cause of hospital admission among individuals with SCD; many patients also encountered infections and ACS. Furthermore, patients who experienced infections and VOC had a lengthier duration of hospital stay. Therefore, it is essential to provide them with comprehensive instructions on various preventive measures against infections and the factors that trigger painful crises.

Keywords: acute chest syndrome; hospitalization; infection; painful crisis; sickle cell disease

DOI: https://doi.org/10.7759/cureus.61185