bims-sicedi 2025-07-06 papers

J Clin Invest. 2025 Jul 03. pii: e192920. [Epub ahead of print]

Blood-storage duration affects hematological and metabolic profiles in patients with sickle cell disease receiving transfusions.

Matthew S Karafin, Abby L Grier, Ross M Fasano, Anton Ilich, David Wichlan, Ada Chang, Sonjile M James, Hailly E Butler, Oleg Kolupaev, Melissa C Caughey, Daniel J Stephenson, Julie A Reisz, Nigel S Key, Joshua J Field, Jane A Little, Steven L Spitalnik, Angelo D'Alessandro.

Patients with sickle cell disease (SCD) frequently receive red blood cell (RBC) units stored near the end of their permissible storage life. To evaluate whether storage duration influences recipient metabolism, clinical chemistry and hematological parameters, we conducted a prospective, randomized, blinded trial comparing transfusions of RBC units stored for ≤10 days versus ≥30 days. Chronically transfused adults with SCD (N=24) received three consecutive outpatient transfusions with randomized-age RBCs, and blood samples from units and recipients were analyzed by metabolomics and clinical chemistry. Transfusion of short-stored units resulted in significantly higher circulating levels of 2,3-bisphosphoglycerate, an essential regulator of oxygen unloading, up to two weeks post-transfusion. Conversely, transfusions of long-stored RBCs were associated with lower hemoglobin and RBC increments, higher iron and transferrin saturation, pro-inflammatory cytokines and metabolites, oxidative stress and markers of renal dysfunction. Plasma and RBC metabolomic profiles revealed time- and storage-age-dependent alterations, particularly affecting glycolysis, purine, and sphingolipid metabolism. Transfusion of long-stored RBCs consistently worsened laboratory surrogates of oxygen delivery and RBC efficacy, and increased the circulating levels of immunomodulatory metabolites and pro-inflammatory cytokines. These findings highlight metabolic and hematologic advantages associated with transfusing fresher RBCs in adults with SCD, independent of immediate clinical outcomes.

Keywords: Clinical Research; Clinical practice; Clinical trials; Hematology; Metabolomics

DOI: https://doi.org/10.1172/JCI192920

Front Biosci (Schol Ed). 2025 Jun 25. 17(2): 38388

Genetic Modifiers of HbF in HbAA and HbAS Women From São Tomé e Príncipe: An Association Study of Common Genetic Variants in BCL11A, MYB, HBG2, and BGLT3.

Licínio Manco, Afonso Marques Morais, Sara Miguel Almeida, Inês Salgado, Luís Relvas, Celdidy Monteiro, Guilherme Queiroz, Celeste Bento.

BACKGROUND: While an increase in fetal hemoglobin (HbF) has no consequences in healthy adults, clinical benefits can be promoted in sickle cell disease (SCD) and β-thalassemia patients. Single-nucleotide polymorphisms (SNPs) in three genomic regions: the HBB gene cluster, the BCL11A gene, and the HBS1L-MYB (HMIP) intergenic region, have been associated with HbF regulation. Therefore, the present study aimed to examine the potential association of SNPs in BCL11A (rs11886868 and rs1427407), HMIP (rs66650371 and rs4895441), HBG2 (rs7482144), and BGLT3 (rs7924684) with HbF levels in an adult population sample from São Tomé e Príncipe (Central Africa).
METHODS: A total of 145 women aged 18 to 49 years were involved in this study, comprising 98 women with the normal hemoglobin (Hb) genotype (HbAA) and 47 with sickle cell trait (HbAS). From the HbAA individuals, we selected a control group of 60 subjects with normal HbF levels, ranging from 0.2% to 1.4% (mean: 0.75%), and a case group of 38 subjects with elevated HbF levels, ranging from 1.8% to 3.7% (mean: 2.35%). In the group of HbAS individuals, the HbF levels ranged from 0.4% to 3.7% (mean: 1.56%). SNP genotyping was conducted using standard molecular methods.
RESULTS: Logistic regression, in the additive model, revealed significant associations with increased levels of HbF for the minor alleles of the two BCL11A SNPs, rs11886868 [C] and rs1427407 [T], in HbAA women (p = 0.00018 and p = 0.00076, respectively). When comparisons of HbF levels were conducted among genotypes in the HbAA women, significant differences were observed for BCL11A SNPs rs11886868 and rs1427407, as well as for the HBG2 rs7482144 and BGLT3 rs7924684 variants. We found no association between HbF levels and the two HMIP variants rs66650371 and rs4895441 in the HbAA women. Among the HbAS women, no statistically significant associations were observed between the six analyzed polymorphisms and HbF levels (p > 0.05).
CONCLUSIONS: We successfully replicated the association between the two well-known BCL11A SNPs, rs11886868 and rs1427407, with HbF levels in women with the normal HbAA genotype from São Tomé e Príncipe. Other signals of association with HbF levels were identified for the SNPs HBG2 (rs7482144) and BGLT3 (rs7924684).

Keywords: BCL11A; BGLT3; HBG2-XmnI; HMIP; HbF regulation; São Tomé e Príncipe

DOI: https://doi.org/10.31083/FBS38388

Ann Hematol. 2025 Jun 30.

Genotype-dependent albuminuria in adult sickle cell disease in Kinshasa.

Yannick Mompango Engole, Jean Robert Rissassi Makulo, Justine Busanga Bukabau, Yannick Mayamba Nlandu, Brady Makanzu, Yannick Mvita, Aliocha Nkodila, François Musungayi Kajingulu, Vieux Momeme Mokoli, Augustin Luzayadio Longo, Marie France Ingole Mboliasa, Clarisse Nsenga Nkondi, Daddy Mbiso Liombo, James Kalunga, Blaise Nkolomoni, Ange Ngonde, Ernest Kiswaya Sumaili.

Albuminuria, which depends on multiple factors, is common in patients with sickle cell disease and can progress to chronic kidney disease. In this study, we investigated the frequency and determinants of albuminuria according to sickle cell disease genotype. This multicentre cross-sectional analytical study of adults with stable sickle cell disease was conducted in Kinshasa. Genotypes were categorised as follows: homozygous, HbSS; heterozygous, HbAS; albuminuria, urinary albumin/creatinine ratio (mg/g): grade A1, < 30; grade A2:30-300; or grade A3, > 300. In total, 247 patients with sickle cell disease were included: 205 homozygous and 42 heterozygous. Albuminuria was prevalent in 50.5% of homozygous and 56.1% of heterozygous patients. The multivariate analysis revealed that the factors independently associated with albuminuria in the homozygous group were age ≥ 30 years (p = 0.037), leg ulcers (p = 0.010), hypertension (p = 0.038), and C-reactive protein level > 6 mg/L (p = 0.033). In the heterozygous group, only hypertension (p = 0.009), C-reactive protein > 6 mg/L (p = 0.006) and a history of vaso-occlusive crisis (p = 0.014) emerged as factors independent factors. More than half of patients with sickle cell disease had albuminuria, which was independently associated with hypertension and inflammation in both groups. Furthermore, there was also an association between in albuminuria and age ≥ 30 years, manifestations of vasculopathy in the homozygous group and a history of vaso-occlusive crisis in the heterozygous group.

Keywords: Albuminuria; Genotype; Sickle cell disease; Steady state

DOI: https://doi.org/10.1007/s00277-025-06362-6

Blood Adv. 2025 Jul 03. pii: bloodadvances.2024015657. [Epub ahead of print]

Sex and genotype specificities of microvasculature and muscle remodeling in sub-Saharan sickle cell trait and disease.

Léo Blervaque, Pablo Bartolucci, Manon Riccetti, Marion Ravelojaona, Angèle N Merlet, Mathilde Noguer, Manon M Rojo, Christophe Hourdé, Cyril Martin, Vincent Pialoux, Barnabas Gellen, Frédéric Galactéros, Samuel Oyono-Enguéllé, Léonard Féasson, Laurent A Messonnier.

Sickle cell disease (SCD) is associated with microvascular and muscle remodeling as well as reduced exercise tolerance. However, SCD-repercussions on microvasculature and muscle remain unknown in women. The present study aimed to compare i) muscle microvascular and energetic characteristics of female and male healthy subjects (CON), carriers of sickle cell trait (SCT) and patients with SCD, and ii) adaptations to endurance training (ET) compared to habitual life (UT) in patients. In SCD, correlations between capillary density and plasma L-selectin (p<0.001) and ICAM (p<0.01) and between capillary diameter and mean corpuscular hemoglobin S concentration (p<0.01) were noticed. The capillary network rarefaction observed in SCD was more pronounced in women than in men (interaction: p<0.01). Muscle hypoxia markers were not different between groups. Compared to CON, the surface area for 100 myocytes was lower in men with SCD (both p<0.001) but not in women. Advanced oxidation protein products were increased in SCD patients and to a greater extent in men (interaction: p<0.02). Components of muscle pH regulation were specifically higher in SCT. Compared to UT, ET saw its microvascular network and oxidative capacities increase, without differences between men and women. Our results suggest that SCD-associated capillary rarefaction and enlargement could be related to disturbed hemodynamics and reduced erythrocytes deformability, respectively. The specific remodeling in female SCD patients included aggravated microvascular remodeling but preserved myocytes. Muscle pH regulation mechanisms appeared specifically up-regulated in SCT carriers. Men and women with SCD improved similarly their microvasculature and muscle energetic characteristics in response to endurance training. NCT02571088.

DOI: https://doi.org/10.1182/bloodadvances.2024015657

Emerg Med Clin North Am. 2025 Aug;pii: S0733-8627(25)00018-5. [Epub ahead of print]43(3): 391-406

Sickle Cell Disease.

Lauren V Ready, Mary Carroll Lee, John C Perkins.

Despite advances in outpatient treatment options, early mortality, chronic pain, and limitations in quality-of-life indices remain substantial for those living with SCD. It is imperative for emergency providers (EPs) to understand their challenging and dual obligation when treating a patient with SCD. First, the EP must aggressively manage the acute pain episode in an objective manner. Secondly, it is equally important to consider concurrent pathology that cannot be missed, such as AChS, pulmonary embolism, sepsis, and splenic sequestration. Finally, the EP should prioritize compassionate care that avoids reinforcing any stigma associated with SCD with subsequent detriment to the patient.

Keywords: Acute chest syndrome; Acute pain episode; Quality of life; Sickle cell disease; Splenic sequestration; Stigma; Vaso-occlusive crisis

DOI: https://doi.org/10.1016/j.emc.2025.03.007