Blood Cells Molecules and Diseases最新文献

Despite several existing laboratory-based studies of hemoglobin (Hb) E (HBB:c.79 G > A)/ β (nucleotide (NT) -28 A > G) (HBB:c.-78 A > G) -thalassemia, no reports have ever provided clinical severity information as well as dependency of blood transfusion. Previously, a comparative study of community- and hospital-recruited Hb E/β-thalassemia subjects was conducted in the lower northern Thailand between June 2020 and December 2021. A mobile medical team visited each community hospital on-site, collecting clinical severity parameters, and conducting Hb and DNA analyses. The control included Hb E/β-thalassemia patients undergoing transfusions. Subgroup study of adult Hb E/β (NT -28 A > G) -thalassemia subjects was subsequently conducted. Additional pediatric individuals were recruited from prenatal diagnosis databases. Twenty adult and nine pediatric subjects were enrolled; all were classified as having mild disease severity. Twenty-two individuals (75.9 %) were asymptomatic. Six adults (20.7 %) required blood transfusion. The mean Hb level of subjects without transfusion (23 [79.3 %]) was 10.77 ± 1.10 g/dL. Hb analysis revealed a distinct EFA pattern with low Hb F fraction. The positive impact of genetic modifiers could not be statistically demonstrated except rs7482144-XmnI. These findings could provide essential information for parents carrying fetuses with Hb E/β (NT -28 A > G) -thalassemia.

Recent evidence suggests that systemic conditions, particularly those associated with inflammation, can affect erythrocyte deformability in the absence of haematological conditions. In this exploratory study, we investigated the relationship between systemic inflammatory status and erythrocyte deformability (using osmotic gradient ektacytometry) in a heterogenous study population consisting of individuals with no medical concerns, chronic conditions, and acute illness, providing a wide range of systemic inflammation severity.

22 participants were included in a prospective observational study. Maximum Elongation Index (EI_max) in ektacytometry served as the readout for erythrocyte deformability. Inflammatory status was assessed using C-reactive protein (CRP) and self-reported symptoms associated with inflammatory activation (Sickness Questionnaire Scores, SicknessQ).

In a univariate linear regression, both CRP and SicknessQ scores significantly predicted EI_max (CRP: F(1,20) = 7.751, p < 0.05 (0.011), R² = 0.279; SicknessQ: F(1,18) = 4.831, p < 0.05 (0.041), R² = 0.212). Sensitivity analyses with multivariable linear regression correcting for age showed concordant findings.

Results suggest a linear relationship between erythrocyte deformability and biochemical and clinical markers of systemic inflammation. Replication of findings in a larger study, and mechanisms and clinical consequences need further in investigation.

Introduction

Telomere length related studies are limited in pediatric marrow failure cases due to difficulty in establishing population specific age related normograms. Moreover, there is paucity of data related to clinical relevance of telomere length in idiopathic aplastic anemia (IAA) and non telomere biology inherited bone marrow failure syndrome (IBMFS) cases. Methodology: Hence, in current study we investigated Relative telomere length (RTL) by RQ-PCR in 83 samples as: healthy controls (n = 44), IAA (n = 15) and IBMFS (n = 24). In addition, we performed chromosomal breakage studies and targeted NGS to screen for pathogenic variants. Results & Conclusion: Median RTL was significantly different between control vs. IBMFS (p-0.002), IAA vs. IBMFS (p-0.0075) and DC vs. non-DC IBMFS (p-0.011) but not between control vs. IAA (p-0.46). RTL analysis had clinical utility in differentiating BMF cases as 75 % (9/12) of DC had short/very short telomeres compared to only 17 % (2/12) of non-DC IBMFS, 7 % (1/15) of IAA and 7 % (3/44) of controls (p < 0.001).

Background

Sickle cell disease (SCD) registries provide crucial real-world data on demographics, epidemiology, healthcare, patient outcomes, and treatment efficacy. This paper presents findings from the Indian SCD Registry (ISCDR) on clinical manifestations, crisis episodes, disease management, and healthcare utilization in patients with SCD from 12 primary health centres (PHCs) in six tribal districts of India.

Methods

The ISCDR was introduced along with a three-tier screening process. Its Android-based application incorporates two electronic case report forms for patient data collection over one year. This paper presents a year's data from the ISCDR's 324 patients with SCD.

Results

Patients with SCD, aged one to 65 years, exhibited varied clinical manifestations. Most patients (85.2 %) were unaware of their SCD status before enrolling in ISCDR. Moderate to severe anaemia was prevalent (66.05 % and 30.56 %, respectively). Pain was a common complaint (80.86 %; CI: 76.17–85.00), while symptoms of stroke included sudden severe headaches (34.57 %; CI: 29.40–40.02). Common splenic sequestration symptoms included stomach pain (42.90 %; CI: 37.44–48.49) and abdominal tenderness (13.27 %; CI: 9.77–17.46), as a sign. Healthcare utilization was high, with 96.30 % receiving treatment and 83.64 % consuming hydroxyurea. Hospitalization occurred for 38.27 % (CI: 32.95–43.81), and 12.04 % (CI: 8.70–16.09) had blood transfusion during last year.

Conclusions

ISCDR serves as a dynamic digital database on SCD epidemiology, clinical aspects, treatment and healthcare utilization. Notably, many patients lacked prior awareness of their SCD status, underscoring the need for improved awareness and care management. Integrating the registry into the national programme can streamline treatment implementation, prioritize management approaches, and optimize individual benefits.

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive genetic disorder characterized by severe immunodeficiency, albinism and coagulation deficiency. Mostly diagnosed in early childhood, this devastating condition is associated with lysosomal abnormalities attributed to the absence or impaired function of lysosomal trafficking regulator caused by mutations in the CHS1/LYST gene. In current study, we report a case of late-onset CHS caused by two novel compound heterozygous CHS1/LYST mutations: c.8407C > T, leading to early termination of translation at residue Gln2803 (p. Gln2803Ter), and a small deletion c. 4020_4031del, resulting in an in-frame deletion of three amino acid residues (p. Asp1343_Val1346del). Both variants retain a large part of the CHS/LYST protein, particularly p. Asp1343_Val1346del, which preserves critical functional BEACH and WD40 domains in the C terminal, potentially maintaining residual activity and alleviating patient symptoms. The timeline of SARS-CoV-2 infection and rapid symptom progression suggests that the viral infection may have trigger the accelerated phase development leading to a poor prognosis.

A graft source for allogeneic hematopoietic stem cell transplantation is umbilical cord blood, which contains umbilical cord blood mononuclear cells (MNCs and mesenchymal stem cells, both an excellent source of extracellular microparticles (MPs). MPs act as cell communication mediators, which are implicated in reactive oxygen species formation or detoxification depending on their origin. Oxidative stress plays a crucial role in both the development of cancer and its treatment by triggering apoptotic mechanisms, in which CD34+ cells are implicated. The aim of this work is to investigate the oxidative stress status and the apoptosis of HL-60 and mononuclear cells isolated from umbilical cord blood (UCB) following a 24- and 48-hour exposure to CD34 + microparticles (CD34 + MPs). The activity of superoxide dismutase, glutathione reductase, and glutathione S-transferase, as well as lipid peroxidation in the cells, were employed as oxidative stress markers. A 24- and 48-hour exposure of leukemic and mononuclear cells to CD34 + -MPs resulted in a statistically significant increase in the antioxidant activity and lipid peroxidation in both cells types. Moreover, CD34 + MPs affect the expression of BCL2 and FAS and related proteins and downregulate the hematopoietic differentiation program in both HL-60 and mononuclear cells. Our results indicate that MPs through activation of antioxidant enzymes in both homozygous and nonhomozygous cells might serve as a means for graft optimization and enhancement.

TAFRO syndrome is a rare systemic inflammatory disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. The diagnosis of TAFRO syndrome can be challenging; however, prompt diagnosis is vital because TAFRO syndrome is a progressive and life-threatening disease. We have showcased five patients with TAFRO syndrome who had similar bone marrow (BM) findings that could be considered the findings that characterize TAFRO syndrome. All patients were treated with corticosteroids and tocilizumab; three of the five patients (60 %) responded positively to the treatment. The unique BM findings observed in this study were megakaryocytes with distinct multinuclei and three-dimensional and indistinct bizarre nuclei (“dysmorphic megakaryocyte”), similar to the megakaryocyte morphology observed in myeloproliferative neoplasms (MPNs). Notably, dysmorphic megakaryocytes were observed in all five cases, whereas only two of the five patients tested positive for reticulin myelofibrosis, and three of the five patients had megakaryocytic hyperplasia, which are considered typical findings of TAFRO syndrome. Thus, the BM findings of dysmorphic megakaryocytes could help in the correct and immediate diagnosis of TAFRO syndrome.

This retrospective study at Beijing Children's Hospital (2020–2023) analyzed surgical procedures and complications in 24 pediatric hemophilia patients undergoing Totally Implantable Venous Access Port (TIVAP) insertion, primarily in the right jugular vein (RJV). We detailed the surgical process, including patient demographics and intraoperative imaging use. The choice of the RJV for TIVAP placement was influenced by its larger diameter and superficial anatomical position, potentially reducing risks like thrombosis and infection. Our findings support the RJV as a safer alternative for port placement in pediatric patients, aligning with current literature. Statistical analysis revealed no significant correlation between complications and baseline characteristics like weight and diagnosis type. However, the length of hospital stay and implant brand were significant risk factors for catheter or port displacement and removal. The limited patient number may introduce bias, suggesting a need for further studies with larger samples. Despite a 14.7 %–33 % complication rate and 5 port removals, the advantages of TIVAP, including reliable venous access, reduced discomfort, and treatment convenience, were evident. Most complications improved with symptomatic treatment, and there were no deaths due to port-related complications, underscoring the impact of TIVAP on improving pediatric hemophilia treatment.

This study aimed to investigate the mechanism of the apoptosis of erythroblasts in rat bone marrow after the exposure to hypobaric hypoxia. Male SD rats were randomly divided into three groups. The hypoxic group was kept in a hypobaric hypoxia chamber at a simulated altitude of 5000 m for 7 and 28 days, respectively. The control group was kept at an altitude of 2260 m. We found that myeloid: erythroid (M:E) ratio was significantly lower after hypoxia exposure and the proportions of polychromatic erythroblasts and orthochromatic erythroblasts significantly increased compared to control group, along with significant increase in the proportion of CD71+ cells and apoptosis rate. The expression levels of caspase-3, Bax, and Cyt-C in CD71+ cells were higher after hypoxia exposure than those in control group, while there was no significant difference in the expression levels of TNFR and Fas. In conclusion, after exposure to hypobaric hypoxia the proliferation of peripheral blood and bone marrow erythroblasts in rats increased, and apoptosis also increased, indicating that bone marrow erythroblasts in rats is regulated by both proliferation and apoptosis, and the mitochondrial pathway is one of the important pathways for apoptosis.