bims-conane 2024-09-01 papers

Blood Adv. 2024 Aug 27. 8(16): 4457-4458

Transfusion. 2024 Aug 27.

Functional biomarkers for sickle cell disease.

Yvette C Tanhehco.

DOI: https://doi.org/10.1111/trf.17992

Nat Cardiovasc Res. 2023 Nov;2(11): 957

Autologous globin-edited HSCs ameliorate sickle cell disease.

Grant Otto.

DOI: https://doi.org/10.1038/s44161-023-00361-4

Nat Rev Urol. 2024 Aug 27.

Quest for a genetic biomarker for sickle cell disease priapism: rationale, progress and implications.

Oluwafolajimi Adesanya, Arthur L Burnett.

DOI: https://doi.org/10.1038/s41585-024-00927-2

Cureus. 2024 Jul;16(7): e65263

Prevalence, Risk Factors, and Complications of Sickle Cell Disease in Saudi Arabia: A Systematic Review.

Nazim F Hamed, Yousef Dakheel Allah Alatawi, Danya Mohammed Zuhair AlKabbani.

This study examined sickle cell disease (SCD) in Saudi Arabia. A systematic search of relevant databases was conducted to identify studies investigating SCD in the Saudi population. Studies were then screened based on predefined criteria and critically appraised for methodological quality. Data was extracted and synthesized to provide an overall picture of the SCD burden in Saudi Arabia. The most commonly reported complications were vaso-occlusive crises (VOC), acute chest syndrome (ACS), acute painful crisis, splenic sequestration, osteomyelitis, aplastic crisis, hemolytic crisis, serious bacterial infections, chronic vascular occlusion (CVO), depression, sickle cell nephropathy (SCN), obstructive sleep apnea (OSA), and renal complications. Reduced blood levels of antioxidant trace elements (Cu, Zn, and Se) may encourage oxidative stress, which in turn may contribute to the pathophysiology of SCD. Infections and ACS were common among young children (<7 years) while pain attacks were common in older children (>7 years). The high rate of hospitalizations among SCD patients highlights the need for better management strategies. Future research should focus on understanding the underlying causes of SCD complications and developing new ways to control them.

Keywords: complications; hemoglobinopathies; prevalence; risk factors; saudi arabia; sickle cell disease; systematic review

DOI: https://doi.org/10.7759/cureus.65263

Int J Mol Sci. 2024 Aug 06. pii: 8578. [Epub ahead of print]25(16):

Novel Insights into Hb Shaare Zedek Associated with β0-Thalassemia: Molecular Characteristics, Genetic Origin and Diagnostic Approaches.

Surada Satthakarn, Wibhasiri Srisuwan, Naowarat Kunyanone, Sitthichai Panyasai.

Hemoglobin Shaare Zedek (Hb SZ) is a rare structural α-Hb variant. Characterizing its genotype-phenotype relationship and genetic origin enhances diagnostic and clinical management insights. We studied a proband and six family members using high-performance liquid chromatography (HPLC), capillary electrophoresis (CE), PCR, and sequencing to analyze α- and β-globin genes and α-globin haplotypes. Pathogenicity predictions and a rapid diagnostic method were developed. The proband, his father, grandfather, and aunt had Hb migrating to the HbH-zone on CE and elevated fetal hemoglobin (HbF) on HPLC. Direct sequencing identified an A to G mutation at codon 56 of the α2-globin gene, characteristic of Hb SZ. Additionally, the proband carried a β-globin gene mutation [HBB.52A>T]. Mild thalassemia-like changes were observed in the proband, whereas individuals with only the Hb SZ variant did not exhibit these changes. Pathogenicity predictions indicated that Hb SZ is benign. The variant can be identified using restriction fragment length polymorphism (RFLP) and allele-specific PCR. The Thai variant of Hb SZ is associated with the haplotype [- - M - - - -]. Hb SZ is a non-pathological variant that minimally affects red blood cell parameters, even when it coexists with β0-thalassemia. HPLC and CE systems cannot distinguish it from other Hbs, necessitating DNA analysis for accurate diagnosis.

Keywords: Premier Resolution HPLC; genetic origin; hemoglobin Shaare Zedek; hemoglobinopathy; α-globin haplotype; α-thalassemia; β-thalassemia

DOI: https://doi.org/10.3390/ijms25168578

J Pediatr Hematol Oncol. 2024 Aug 26.

Haploidentical Stem Cell Transplants in Children With Sickle Cell Disease: A Single Center Real-world Experience.

Samer Abdelkader, Rikin Shah, David Crawford, Ashley Baker, Anand Srinivasan.

DOI: https://doi.org/10.1097/MPH.0000000000002946

Int J Mol Sci. 2024 Aug 16. pii: 8928. [Epub ahead of print]25(16):

Loss-of-Function Variants in SUPT5H as Modifying Factors in Beta-Thalassemia.

International Hemoglobinopathy Research Network (INHERENT)

It is well known that modifiers play a role in ameliorating or exacerbating disease phenotypes in patients and carriers of recessively inherited disorders such as sickle cell disease and thalassemia. Here, we give an overview of the literature concerning a recently described association in carriers of SUPT5H Loss-of-Function variants with a beta-thalassemia-like phenotype including the characteristic elevated levels of HbA2. That SUPT5H acts as modifier in beta-thalassemia carriers became evident from three reported cases in whom combined heterozygosity of SUPT5H and HBB gene variants was observed to resemble a mild beta-thalassemia intermedia phenotype. The different SUPT5H variants and hematologic parameters reported are collected and reviewed to provide insight into the possible effects on hematologic expression, as well as potential disease mechanisms in carriers and patients.

Keywords: SUPT5H; beta-thalassemia; hematology; hemoglobin; modifying factor; molecular diagnosis; β-thalassemia intermedia

DOI: https://doi.org/10.3390/ijms25168928

Hematol Rep. 2024 Aug 01. 16(3): 512-522

Investigation of Delayed Transfusion Reactions in Sickle Cell Disease Patients Polytransfused in the Brazilian Amazon.

Lorena Alves Santos, Anne Cristine Gomes de Almeida, Andrea Monteiro Tarragô, Nina Rosa Gonçalves da Silva, Juliana Nascimento Vitoriano da Silva, Mônica Moura de Souza, Monik Oney Oliveira Nascimento, Marcelo Reis do Nascimento, Ana Caroline Dos Santos Castro, Cinthia Xerez de Albuquerque, Evilázio Cunha Cardoso, José Pereira Moura Neto, Sérgio Roberto Lopes Albuquerque.

BACKGROUND: Sickle cell disease (SCD) affects approximately 100,000 people in the United States and millions worldwide, with the highest prevalence of 70% of SCD being found in individuals of African ethnicity. Delayed hemolytic, alloimmunization, and anamnestic transfusion reactions in multiple transfusion patients need to be investigated and managed to avoid a worsening of the patient's clinical status.
OBJECTIVE: This paper aims to investigate delayed transfusion reactions in SCD patients who were polytransfused in the Brazilian Amazon.
MATERIAL AND METHODS: The clinical and laboratory indicators of SCD patients with more than four transfusions were investigated. The patients were treated at the Fundação Hospitalar de Hematologia e Hemoterapia do Estado do Amazonas, Brazil.
RESULTS: A total of 44 polytransfused patients with SCD were followed. Regarding Rh phenotype, it was possible to observe a frequency of 26.6% (12) patients with the RZRZ (DCE/DCE) phenotype, in addition to 4.5% (two) patients with RH and RHCE variants. It was also possible to observe 20.5% (nine) patients with an alloimmunization reaction, who presented the following alloantibodies: anti-RhD, anti-E, anti-K, anti-Jkb, anti-N, anti-S, and anti-Dia, two of which are unidentified. Of these, four (44.4%) patients also presented autoantibodies, anti-e, and three unidentified antibodies, and four (44.4%) patients presented an anamnestic reaction, with anti-RhD, K, and Jkb antibodies. Of the 44 patients monitored, 54.4% (24) had clinical and laboratory indicators of a delayed hemolytic reaction.
CONCLUSION: Delayed transfusion reactions, often neglected, occur frequently. Therefore, transfusions need to be monitored for at least 28 days, with medical investigation of clinical and laboratory indicators to make greater use of this therapeutic resource.

Keywords: alloantibody; delayed transfusion reactions; hemolysis; sickle cell disease

DOI: https://doi.org/10.3390/hematolrep16030049

Cells. 2024 Aug 16. pii: 1363. [Epub ahead of print]13(16):

Role of Piezo1 in Terminal Density Reversal of Red Blood Cells.

Kuntal Dey, Ankie M van Cromvoirt, Inga Hegemann, Jeroen S Goede, Anna Bogdanova.

Density reversal of senescent red blood cells has been known for a long time, yet the identity of the candidate ion transporter(s) causing the senescent cells to swell is still elusive. While performing fractionation of RBCs from healthy individuals in Percoll density gradient and characterization of the separated fractions, we identified a subpopulation of cells in low-density fraction (1.02% ± 0.47) showing signs of senescence such as loss of membrane surface area associated with a reduction in band 3 protein abundance, and Phosphatidylserine (PS) exposure to the outer membrane. In addition, we found that these cells are overloaded with Na+ and Ca2+. Using a combination of blockers and activators of ion pumps and channels, we revealed reduced activity of Plasma membrane Ca2+ ATPase and an increase in Ca2+ and Na+ leaks through ion channels in senescent-like cells. Our data revealed that Ca2+ overload in these cells is a result of reduced PMCA activity and facilitated Ca2+ uptake via a hyperactive Piezo1 channel. However, we could not exclude the contribution of other Ca2+-permeable ion channels in this scenario. In addition, we found, as a universal mechanism, that an increase in intracellular Ca2+ reduced the initially high selectivity of Piezo1 channel for Ca2+ and allowed higher Na+ uptake, Na+ accumulation, and swelling.

Keywords: Piezo1; calcium; red blood cells; senescence; terminal density reversal

DOI: https://doi.org/10.3390/cells13161363