bims-sicedi Biomed News
on Sickle cell disease
Issue of 2025–09–28
four papers selected by
João Conrado Khouri dos Santos, Universidade de São Paulo



  1. Lancet Haematol. 2025 Sep 18. pii: S2352-3026(25)00260-1. [Epub ahead of print]
      
    DOI:  https://doi.org/10.1016/S2352-3026(25)00260-1
  2. Hemasphere. 2025 Sep;9(9): e70209
    SickleGenAfrica Network
      Sickle cell disease (SCD) is characterized by chronic hemolysis, resulting in the release of extracellular heme, which contributes to oxidative stress and inflammation. Heme oxygenase-1 (HO-1), an inducible enzyme that degrades heme into cytoprotective by-products, plays a critical role in mitigating heme-induced toxicity. This study analyzed serum HO-1 levels in 2309 individuals with SCD (53% female; median age: 12 years) from the SickleGenAfrica cohort, comprising 57% hemoglobin SS disease (Hb SS), 30% hemoglobin SC disease (Hb SC), 3.1% Hb sickle beta plus thalassemia (Sβ+ thalassemia), and 9.9% Hb S-hereditary persistence of fetal hemoglobin (Hb S-HPFH). Median HO-1 levels were threefold higher in children under 16 years (69.8 ng/mL; interquartile range [IQR]: 29.8-137.6) compared to adults (23.1 ng/mL; IQR: 7.8-62.4; P < 0.001), with peak levels observed in the 6-10-year age group. Across all subgroups, including sex, genotype, and hydroxyurea use, children consistently exhibited higher HO-1 levels than adults, with Hb SS patients showing the highest levels. Haptoglobin and hemopexin, key scavengers of hemoglobin and heme, respectively, were depleted in all patients, particularly in children. Overall, HO-1 levels in SCD patients were markedly elevated compared to healthy populations. These findings highlight the pronounced elevation of HO-1 in pediatric SCD patients, suggesting its potential protective role against heme-induced toxicity, especially during childhood.
    DOI:  https://doi.org/10.1002/hem3.70209
  3. Am J Hematol. 2025 Sep 24.
      
    Keywords:  cardiac fibrosis; cardiomyopathy; diastolic dysfunction; hemoglobinopthy; sickle cell disease; thalassemia
    DOI:  https://doi.org/10.1002/ajh.70073
  4. Lancet Haematol. 2025 Sep 18. pii: S2352-3026(25)00235-2. [Epub ahead of print]
       BACKGROUND: Sickle cell disease, one of the most common genetic conditions in the UK, is often considered a neglected disorder, but rigorous quantitative evidence to support this view is scarce. Comparative research of multiple conditions offers an effective way to document inequity and to guide public health policies. Therefore, we aimed to compare indicators of inequity in research and funding for sickle cell disease, cystic fibrosis, and haemophilia in the UK.
    METHODS: In this descriptive comparative study, we compiled publicly available data on disease prevalence for sickle cell disease, cystic fibrosis, and haemophilia, alongside seven comparative indicators: the number and value of grants from UK public health research funders (the Wellcome Trust, the National Institute for Health and Care Research, and UK Research and Innovation); resources available to dedicated charities (the Sickle Cell Society, the Cystic Fibrosis Trust, and the Haemophilia Society); characteristics of disease registries (the National Haemoglobinopathy Register, the UK Cystic Fibrosis Registry, and the UK National Haemophilia Database); the number of registered clinical trials (the National Library of Medicine Clinical Trials and the EU clinical trials register); number of scientific publications (PubMed); number of drug approvals (the Medicines and Healthcare products Regulatory Agency); and online disease awareness (Google Trends and Glimpse). We conducted descriptive analyses, including counts, proportions, means, and ratios.
    FINDINGS: We found marked differences in the seven indicators considered. Sickle cell disease was usually the most neglected condition, particularly when accounting for the number of people affected. The mean annual research funding per person was almost four times higher for cystic fibrosis (£704 [95% CI 697-710]) than for sickle cell disease (£184 [172-196]), and two times higher than for haemophilia (£315 [226-404]). There was one clinical trial per 273 people with sickle cell disease, compared with one trial per 53 and 55 people for cystic fibrosis and haemophilia, respectively. The mean annual number of publications was almost twice higher for cystic fibrosis (2431) than for sickle cell disease (1359) or haemophilia (1193).
    INTERPRETATION: The comparative evidence provided support the view that sickle cell disease is neglected compared with cystic fibrosis and haemophilia in relation to research and funding in the UK. The highest value for each indicator, often observed for cystic fibrosis, provides a benchmark target for the other two conditions. More dedicated research funding would likely have a ripple effect on other indicators, which could guide public health policies and have a major effect on the quality of life of people living with sickle cell disease.
    FUNDING: NHS Race and Health Observatory.
    DOI:  https://doi.org/10.1016/S2352-3026(25)00235-2