bims-sicedi 2025-08-03 papers

Pediatr Blood Cancer. 2025 Aug 01. e31951

The Protective Effect of Fetal Hemoglobin on Retinal Damage in Sickle Cell Disease Patients: A Correlation with Optical Coherence Tomography, Hematologic Parameters, and Hydroxyurea Treatment.

Jing Jin, Pimpiroon Ploysangam, Dorothy H Hendricks, Robin E Miller.

PURPOSE: The protective effect of fetal hemoglobin (HbF) on retinal health in patients with sickle cell disease (SCD) has been well recognized. Hydroxyurea, a disease-modifying agent, induces HbF production and modifies hematologic parameters. This study investigated the correlation between retinal damage on optical coherence tomography (OCT) and HbF levels. Additionally, it compared retinal OCT, HbF, and other hematologic laboratory parameters in patients treated with/without hydroxyurea.
METHODS: In this prospective, observational study, 138 patients with SCD underwent ophthalmologic examination, including OCT. Hematologic values and treatment history were obtained from medical records. Analyses focused on correlations between HbF levels and hematologic markers, HbF trends with age in children with/without abnormal retinal OCT, and the impact of hydroxyurea treatment on HbF levels and OCT results.
RESULTS: Children with normal retinal OCT exhibited a slower age-related decline in HbF levels before age 15 years compared with those with abnormal OCT. HbF levels showed a strongly negative correlation with markers of hemolysis and inflammation and a positive correlation with hemoglobin. Hydroxyurea treatment was associated with elevated HbF levels and a shift in hematologic profile toward those observed in patients with normal OCT findings. Children treated with hydroxyurea exhibited slower progression of macular thinning with age.
CONCLUSIONS: Children with normal OCT findings maintained higher HbF levels and showed a slower decline with age. Hydroxyurea treatment increases HbF levels, improves hematologic profiles, and reduces the likelihood of retinal abnormalities. Further research is needed to elucidate the mechanisms behind these observations and validate the findings in larger datasets.

Keywords: OCT; fetal hemoglobin; hydroxyurea; sickle cell retinopathy

DOI: https://doi.org/10.1002/pbc.31951

Semin Thromb Hemost. 2025 Jul 24.

Red Blood Cell Extracellular Vesicles as Key Players in Thromboinflammation.

Denis F Noubouossie, Nigel S Key.

Thromboinflammation is an emerging concept which highlights the interactions between coagulation and inflammation in various disease states. Activation of coagulation and inflammation are both hallmarks of hemolytic diseases. However, the mechanisms by which they cause adverse outcomes in hemolytic disorders is incompletely understood. The existing literature suggests that red blood cells (RBCs) play a role in thrombosis and in immune regulation. RBCs release extracellular vesicles (RBC-EVs) with increased numbers found in the circulation of patients with hemolytic disorders. In this review, we summarize the existing literature addressing the interaction of RBC-EVs with coagulation and inflammatory pathways in vitro and in vivo. Additionally, we discuss the potential contribution of RBC-EV-induced thromboinflammation in the pathogenesis of certain complications of sickle cell disease as a model of a severe hemolytic disorder.

DOI: https://doi.org/10.1055/a-2664-0871

Sci Rep. 2025 Jul 28. 15(1): 27523

Clinical, laboratory, radiological features, and outcome of acute fat embolism syndrome in sickle cell disease.

Alkindi Salam, Raniga Sameer, Al-Ajmi Eiman, Al-Farsi Khalil, Khan Hammad, Nuzhat Khaleeq Unnisa, Al-Busaidi Mujahid, Al-Azri Faisal, Gujjar Arunodaya, Al-Asmi Abdullah, Al-Maawali Anwaar, Ramachandiran Nandagopal, Pathare Anil V.

Non-traumatic fat embolism syndrome (FES) affecting brain, lung and hematopoietic system is a rare, but a serious complication of sickle cell disease (SCD), resulting from bone marrow necrosis. SCD-related FES is rare, with the spectrum of clinical, laboratory, radiological manifestations and patient outcome is not fully understood. After medical research & ethics committee approval, retrospectively, SCD-FES patients at our centre, were reviewed between January 2006 to December 2023. 27 patients (17 males, 10 females) with a median age of 24 years and length of hospital stay of 24 (16-38) days were enrolled. They had fever, chest/back pain, cough and crepitation in 100%, 96%, 56% and 100% respectively, with neurological manifestations in 96%. Abnormal chest X-rays and CT scans were observed in 96%, and 100% respectively. Patients had significant anemia, reticulocytopenia, and thrombocytopenia, with raised WBC (p < 0.05). There was a significant rise in LDH, ALP, Ferritin and C-reactive protein levels. All patients received antibiotics, and exchange transfusions, whereas 24%, 76% required non-invasive ventilation (NIV) and mechanical ventilation respectively, with 18.5% mortality. FES is a rapidly progressive respiratory and neurological syndrome, characterized by hypoxia, and cytopenia, with raised inflammatory markers, raised LDH and ALP, with distinctive multiple cerebral microbleeds.

Keywords: Bone marrow necrosis; Exchange transfusion; Fat embolism syndrome; Parvovirus B19; Sickle cell disease

DOI: https://doi.org/10.1038/s41598-025-11983-y

PLoS One. 2025 ;20(7): e0329064

The pattern of lung function tests in children with sickle cell disease: A case-control study.

Abinaya Kannan, Gaurav Sarnaik, Nikita Agarwal, Atul Jindal.

BACKGROUND: Sickle cell disease (SCD) is major inherited disease linked to a pro-inflammatory state, with a widespread involvement seen in all organ systems with lungs being no different. This research aims to analyze pulmonary function tests and fractional exhaled nitric oxide (FeNO) levels of children diagnosed with SCD and comparing them with healthy controls.
METHODS: The study involved 100 children with SCD in stable state of health, without pain, crises, or acute illnesses for at least 1-month, and aged between 6-20 years and 100 age- and height-matched controls. Those with spinal deformities, acute or chronic cardiorespiratory symptoms, and cigarette smoking (in parents) were excluded. Measurements of forced vital capacity(FVC) and forced expiratory volume in one second(FEV1) were conducted using an automated single-breath vitalograph. FeNO was recorded using a hand-held device(NIOX MINO). Data werecollected and analyzed.
RESULTS: Children with SCD had significantly lower pulmonary function values compared to controls: FEV1 median difference: 33.5% (95% CI: 27.2-38.0; p < 0.0001), FVC: 25.4% (95% CI: 30.0-32.25; p < 0.0001), FEV1/FVC: 0.088 (95% CI: 0.075-0.083; p < 0.0001), Peak Expiratory Flow Rate (PEFR): 24.8% (95% CI: 16.38-33.8; p < 0.0001), FeNO: 8.17 ppb (95% CI: 5.77-12.65; p < 0.0001). Pulmonary function test (PFT) abnormalities were associated with younger age (p = 0.0022). Age (p = 0.0011) was significantly associated with PFT severity, while blood transfusion frequency, and fractional exhaled nitric oxide (FeNO) levels were not. Increased weight (p = 0.001) and longer duration of hydroxyurea (p = 0.011) were associated with improved PFT severity (based on FEV1 z-scores).
CONCLUSIONS: Children with SCD often exhibit restrictive, obstructive, or mixed pulmonary function patterns. FeNO levels donot correlate with PFT severity.

DOI: https://doi.org/10.1371/journal.pone.0329064