Hemoglobin最新文献

Despite proven efficacy, only 70% of eligible individuals in the U.S. are vaccinated against Streptococcus pneumoniae. This is especially concerning for patients with sickle cell disease (SCD), as they are susceptible to invasive pneumococcal disease owing to functional asplenia. Early and complete vaccination is crucial in preventing pneumococcal sepsis and its complications, including the rare but often fatal fat embolism syndrome. Here, we report a case of an adolescent male with Hemoglobin SC (HbSC) disease who presented to our pediatric emergency department (ED) with abdominal and back pain. Notably he had received all vaccinations according to published guidelines, however had not yet received the expanded pneumococcal vaccine. He was in his usual state of health the previous day. He arrived to the ED mildly febrile, tachypneic, and tachycardic with altered mental status. His condition rapidly deteriorated into acute respiratory failure, coagulopathy, and multiorgan dysfunction syndrome. Unfortunately, he succumbed following multiple cardiac arrests less than 12 hours into his illness course. This case highlights to pediatric and adolescent providers that invasive pneumococcal disease remains a significant risk for vaccinated, adolescent patients, even with mild SCD genotypes. Moreover, it underscores the critical importance of early, complete pneumococcal vaccination in SCD patients. The newer expanded pneumococcal vaccines could enhance protection for this vulnerable population.

Hemoglobin A1c (HbA1c) is a clinically useful parameter, considered the standard-of-care for diagnosing and monitoring type 2 diabetes mellitus. However, the presence of Hb variants, including Hb Montfermeil, may interfere with HbA1c assay, affecting the accuracy of the results. Here, we report the first case diagnosed in Portugal of this rare hemoglobin variant.

Sickle cell disease (SCD) is a genetic disorder with a diverse spectrum of clinical presentation, often determined by inherited β^S gene haplotypes. Ghana, a country with a significant SCD burden, lacks population haplotype frequency data, hindering anthropological, genetic, and clinical understanding and management of the disease. A prospective sample of 191 SCD patients (sickle cell anemia; homozygous HbSS) was recruited at the Korle-Bu Teaching Hospital, Accra. Identification of β^S gene haplotypes was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Hematological tests were performed using routine laboratory procedures. Kruskal-Wallis ANOVA with Dunn post-hoc was used to compare the hematological parameters. Multinomial probability models were used to compare the frequencies of the observed haplotypes with those reported in other African countries. The Atypical haplotype was disproportionately prevalent (58%), followed by the Bantu/CAR (20%) and Benin (10%) haplotypes. Significant differences were observed between the haplotypes in lymphocyte count, platelet count, sodium and potassium levels (P < 0.001). In addition, disease severity varied significantly between haplotypes (P = 0.010), with notable differences between the Atypical and Bantu/CAR haplotypes (P_FDR = 0.020). Multinomial probability testing revealed a substantial deviation from the expected haplotype distribution, highlighting significant differences in haplotype frequencies between Ghana and other African countries. The Wright-Fisher model showed that the variation in Arab-Indian haplotype frequency reached zero by the 100^th generation. Our findings highlight the need to study haplotype composition in Ghana to identify population-specific risk factors and tailor public health interventions to better manage patient needs.

Cognitive impairment is a common and dreaded complication of sickle cell disease (SCD), profoundly affecting patients' quality of life, education, and employment. Despite its significance, there is a striking lack of guidance on optimal screening strategies, with existing tools often skewed by biases related to language proficiency and educational background, leaving many patients undiagnosed and unsupported. The Rowland Universal Dementia Assessment Scale (RUDAS) was specifically designed for cognitive screening in multicultural populations. We hypothesized that in adults with SCD, RUDAS performance is less influenced by educational attainment when compared to the Montreal Cognitive Assessment (MoCA). We conducted a cross-sectional study of adults with SCD who underwent cognitive screening at the Henri-Mondor Hospital using RUDAS and MoCA. Educational attainment was scored as the years of schooling for the highest completed diploma (HLE). Abnormal RUDAS (<28) and MoCA (<26) scores were found in 55/73 (75.3%) and 52/73 (71.2%). Both scores increased significantly with HLE (p < 0.001). Adding 1 point for those with the HLE < 12 years significantly mitigated the effect of education on RUDAS but only partially for MoCA (p = 0.26 and p = 0.003). In an independent cohort of 252 adults, this adjustment for HLE significantly lessened the effect of education on RUDAS. These results suggest there is an educational bias in neurocognitive screening of adults with SCD. We propose that the RUDAS adjusted for HLE is a promising novel strategy to systematically identify those in need of comprehensive neurocognitive assessment.

Molecular characterization was performed for investigation of β-globin gene cluster in a pregnant Chinese female with mild microcytic hypochromic anemia accompanied with complicated hemoglobin fractions. Routine hematological parameters and hemoglobin analyses were conducted using an automated cell counter and capillary electrophoresis, separately. Long-read single molecule real time (SMRT) sequencing was employed to molecularly characterize this individual. Hematological indices showed mild microcytic hypochromic anemia, and hemoglobin analyses demonstrated normal HbA2 percentage of 2.3% and increased HbF value of 13.1% in this female. SMRT thalassemia genetic testing showed a heterozygous β⁺ mutation HBB:c0.316-197C > T (β^{IVS-II-654 (C>T)}) and heterozygous HBG2:c.-211C > T (-158Gγ (C > T)), which has independently been reported to result in elevated HbF levels. A variant HBD: c.-127T > C (-77 (T > C)) was also identified in the promoter region, which has been frequently reported to result in normal HbA2 levels in patients with β-thalassemia. All the three variants were further validated by Sanger sequencing. Moreover, SMRT analysis unraveled a novel duplicated structural variation of HBG1/HBG2 (^Gγ^Aγ/^{-158(C>T)GγGγGγAγ}), a rearrangement of four γ-globin genes including one entire HBG1 and three entire HBG2 in one chromosome. We herein first described a novel structural quadruplet γ-globin genes of HBG2 by SMRT and reported the molecular characterization of a complex thalassemia with variants involving HBG1/HBG2, HBD and HBB genes. Our work may facilitate genetic counseling and bring insight into future diagnosis of complex thalassemia.

Sickle cell disease and β-thalassemia are important health problems in Middle Eastern countries. Transfusion is the cornerstone of the management in these disorders, and red blood cell alloimmunization is among the well-recognized adverse effects associated with it. We reviewed the literature on published studies on alloimmunization prevalence, its associated risk factors, and transfusion policies employed in these countries. Our review included 39 studies on thalassemia (including 9005 patients), and 19 on sickle cell disease (including 3867 patients). The mean alloimmunization prevalence rate in thalassemia was 13.0% (95% CI: 10.0-15.0%), while that in sickle cell disease was 14.0% (95% CI: 10.0 - 19.0%). The distribution of the prevalence rates showed considerable heterogeneity in both diseases. The most frequent alloantibodies detected were anti-K (25.9%), Anti-E (21.8%), and Anti-D (9.2%), with Rhesus and K antibodies comprising 74.2% of all antibodies detected. Some risk factors were significant in several studies, including older age, female sex, older age at first transfusion, number of transfused units, and splenectomy. The prevalence of alloimmunization was significantly higher in retrospective studies compared to cross-sectional ones, in both thalassemia and sickle cell disease (P = 0.04 in each). This review reaffirmed the need to provide ABO+Rhesus + K matched blood to hemoglobinopathy patients in the Middle East, and the need for more research on Rhesus variants in this part of the world.

Calcium channel blockers (CCBs) for long-term (L) and transient (T) calcium channels (LTCC and TTCC) on cardiomyocytes have been suggested to manage iron-induced cardiomyopathy in transfusion-dependent thalassemia patients. However, the results of clinical trials on the effectiveness of CCBs have been conflicting. Here, we systematically reviewed previous studies to investigate the potential factors that could act as therapeutic modifiers and explain these discrepancies. This systematic review was conducted employing the PRISMA guideline to retrieve clinical trials and animal studies investigating the efficacy of CCBs. Studies in the following databases were collected: Web of Science, PubMed, Scopus, Google Scholar, Clinical Trials, Iranian Registry for Clinical Trials, and Cochrane CENTRAL. Keywords included the trade and generic names of various CCBs, thalassemia, and cardiomyopathy. Our Primary search resulted in 297 studies, of which 21 (n = 7 trials and n = 14 animal studies) were further analyzed. The most important parameters that could potentially influence the clinical effectiveness of CCBs in managing iron-induced cardiomyopathy included baseline cardiac iron content, diversity of iron entry routes (LTCCs, TTCCs, DMT-1, etc.), type of CCBs used, iron-induced irreversible functional/structural cardiac changes, iron-Ca²⁺ joint metabolic dysregulation, deregulated expression of LTCCs and TTCCs, interaction of CCBs with iron chelators, disease-related complications, interactions of CCBs with various supplements used by patients, vitamin D and other nutrient deficiencies, and duration of treatment with CCBs. These items should be considered in future trials to draw more robust conclusions about the effectiveness of CCBs in preventing cardiac iron deposition and associated cardiomyopathy in TDT patients.

Beta (β) thalassemia is an inherited disorder that occurs following mutations or deletions in the β globin gene. Rarely, it is caused by variants in genes coding for erythroid transcriptional factors or trans-acting factors. Here, we report three novel variants of SUPT5H revealed by next generation sequencing. This, gene has been progressively acknowledged as a mimicker of β thalassemia trait in two independent individuals and one family. These individuals have the same features, including hypochromic microcytic indices, increased Hb A₂ levels, without mutations in the β globin gene. The three novel SUPT5H variants identified in this study (c.1168_1169del, c.2688del and c.307+1G>A) are frameshift variants leading to a premature stop codon or an intronic variant predicted to alter the splice site consensus sequence by in silico software. All three variants are characterized as Loss-of-Function variants either by generating a truncated protein or haplo-insufficiency due to nonsense-mediated decay. These findings confirm the general observation that most variants in SUPT5H associated with a β thalassemia trait phenotype are Loss-of-Function variants. This gene should be considered as a potential target gene in the genetic diagnosis of any unsolved cases of increased HbA₂ and unexplained inconsistency of phenotype and genotype of β thalassemia intermedia.

Hemoglobin (Hb) F, or fetal hemoglobin, is the predominant Hb in fetuses and is converted to adult hemoglobin (Hb A) at the age of 2 years. However, high Hb F levels in adults are typically present in conditions such as β-thalassemia disease and high Hb F determinants including large deletional β-globin gene clusters, and hereditary persistence of fetal hemoglobin (HPFH). The accurate detection of these conditions is crucial for effective disease management and genetic counseling. Several molecular techniques have been used to identify high Hb F determinants but require advanced instrumentation, highly skilled personnel, high cost, long time duration, and post-PCR processing. This study aimed to develop a rapid and cost-effective molecular assay for detecting common high Hb F determinants using colorimetric loop-mediated isothermal amplification (LAMP) with phenol red assays. We focused on the detection of HPFH6, Asian Indian inv-del (^Aγδβ)⁰-thalassemia, and Thai del-inv-ins (^Aγδβ)⁰-thalassemia. A total of 331 DNA samples encompassing 21 genotypes were screened using the developed LAMP assays, which were optimized to detect these determinants within 60-70 min. The assays showed high sensitivity (100%) and specificity (99.6-100%) in each mutation with detection limits of 2.5 ng/reaction. Validation by comparison with conventional methods confirmed the efficacy of the LAMP assays, which is simple, inexpensive, and suitable for use in low-resource settings. Rapid performance, visual detection, and accurate diagnosis may be useful for genetic counseling, particularly in Thailand and Southeast Asia. This innovation is suitable for application in thalassemia screening programs, especially in remote areas.