bims-sicedi 2025-07-13 papers

Ann Hematol. 2025 Jul 08.

Rapid withdrawal of voxelotor can precipitate sickle cell disease related crisis.

Salam Alkindi, Ahmed Al Subhi, Anil Pathare.

Sickle cell disease (SCD) is an inherited disorder characterized by abnormal mutation leading to formation of sickle red blood cells. The initial step is the formation of polymers and precipitation of Hemoglobin within the cell. voxelotor is a novel anti-polymerization drug approved for treatment of patients with SCD, resulting in improved hemoglobin level. Recently its clinical development was suspended, as concerns were raised regarding its safety and efficacy. We have evaluated 11 patients who were stable, on voxelotor for a mean period of 191 weeks (range, 8-369). We observed that upon its withdrawal, 8 patients (73%) showed a rapid onset of vaso-occlusive crisis, within a median of 4.7 days, precipitating hemolysis, with a significant drop of Hb, raised reticulocytes, bilirubin, and lactic dehydrogenase. Also, one patient (9.1%) developed acute chest syndrome, whereas five (45.5%) patients needed blood transfusions. Our data confirms that rapid withdrawal of voxelotor could precipitate severe SCD-related crisis.

DOI: https://doi.org/10.1007/s00277-025-06503-x

Clin Hemorheol Microcirc. 2025 Jul 08. 13860291251357796

Differences in oxygen-gradient ektacytometry parameters and blood viscosity between patients with sickle cell anemia and patients with sickle cell-hemoglobin C disorder.

Philippe Connes, Marie Martin, Camille Boisson, Emeric Stauffer, Céline Renoux, Philippe Joly, Solene Poutrel, Carine Halfon-Domenech, Alexandra Gauthier, Elie Nader.

Oxygen-gradient ektacytometry (oxygenscan) has been recently used in the context of sickle cell disease (SCD) to determine the ability of red blood cells (RBCs) to deform in normoxia and during deoxygenation. While several studies focused on the determinants of oxygenscan parameters in the homozygous form of SCD (i.e., HbSS), very few studies focused on hemoglobin SC disease (HbSC). Oxygenscan parameters were compared between HbSS (N = 304) and HbSC (N = 58) patients, with or without hydroxyurea (HU). RBC deformability measured in normoxia or at low oxygen level was lower in HbSS patients without HU compared to HbSS patients with HU and HbSC patients with or without HU. The propensity of RBCs to sickle during deoxygenation was greater in HbSS than in HbSC patients. Although no significant impact of HU was observed on RBC deformability/sickling in HbSC patients, those with HU had lower blood viscosity. The ability of RBC to recover their maximum deformability after a deoxygenation/reoxygenation cycle was lower in HbSC compared to HbSS patients. Finally, oxygenscan parameters and routine hematological parameters correlated differently in HbSS and HbSC patients. Our study showed difference in oxygenscan parameters between HbSS and HbSC individuals that could partly explain the difference in the clinical expression of SCD.

Keywords: oxygen gradient ektacytometry; red blood cell deformability; sickle cell disease; sickling

DOI: https://doi.org/10.1177/13860291251357796

Hematol Transfus Cell Ther. 2025 Jul 09. pii: S2531-1379(25)00205-6. [Epub ahead of print]47(3): 103937

Investigation of haematological, inflammatory parameters and the incidence of alloimmunization in multi-transfused sickle cell diseased patients.

Florence Ifechukwude Aboderin, Taofeeq Oduola, Glenda Mary Davison, Oluwafemi Omoniyi Oguntibeju.

INTRODUCTION: Sickle cell disease is a haemoglobinopathy caused by an aberrant mutation of the beta chain with the amino acid valine replacing glutamic acid at the 6th position. Patients with sickle cell disease suffer from complications including chronic inflammation and the development of allogeneic antibodies due to multiple blood transfusions. This study investigated the association between haematological, inflammatory markers and alloimmunization in multi-transfused patients with sickle cell disease.
METHODS: This was a cross-sectional study, that enrolled 100 participants; 50 young adults (18-48 years) with homozygous sickle cell disease (Sickle cell Group) from the Obafemi University Health Centre in Nigeria, and 50 age and sex matched individuals who did not have the disease (Control group) but who had also received blood transfusions. Complete blood counts and differentials were processed on an auto-analyser (SFRI H18 Light, France). Red cell antigen identification used the saline and anti-human globin method while the abnormal haemoglobinopathy was evaluated using electrophoresis. ABO and Rhesus blood groups were analysed using a direct method on tile, and the determination of inflammatory markers including C-reactive protein, tumour necrosis factor-alpha, interleukin-6, and interleukin-1β was by the enzyme-linked immunosorbent assay technique. The data were statistically analysed using SPSS version 24.0 and GraphPad Prism. Additionally, the student t-test and Chi-square test were employed as appropriate. Data were presented as mean ± standard deviation, with a p-value <0.05 considered statistically significant.
RESULT: As expected, the Sickle Cell group had an increased rate of alloimmunisation and significantly reduced haemoglobin and red cell parameters except for the mean cell volume. Although both groups had platelet counts within the reference range the Sickle Cell group had significantly higher counts than the Control group. The Sickle Cell group displayed evidence of inflammation with significantly increased levels (p-value = 0.001) of C-reactive protein and tumour necrosis factor-alpha. This was supported by higher white cell counts and neutrophilia. The majority of the antibodies detected in sickle cell disease were anti-Kell, Jka and Fya while the controls showed a higher prevalence of anti-M and Kell antibodies. Despite the elevated inflammatory markers, no significant correlation was observed between these and the rate of alloimmunization.
CONCLUSION: In this study, the Sickle Cell group had an elevated rate of alloimmunization with higher levels of anti-kell, Jka and Fya as well as inflammatory markers. However, despite these findings, no significant correlation between inflammatory markers and alloimmunization could be detected. This suggests that elevated alloimmunization rates are multifactorial and involve other processes which require further investigation.

Keywords: Alloimmunization; Haematological; Inflammatory parameters; Multi transfused; Sickle cell disease

DOI: https://doi.org/10.1016/j.htct.2025.103937

Health Sci Rep. 2025 Jul;8(7): e70960

The Association of Serum Level of TGF-β1 and Clinical Manifestations in Sickle Cell Anemia: A Case-Control Study.

Fatemeh Bakhshipour, Bita Bandar, Fatemeh Bineshfar, Najmeh Nameh Goshay Fard, Azar Babaahmadi, Najmaldin Saki, Kaveh Jaseb.

Background and Aims: Sickle cell anemia (SCA) is an inherited red blood cell disorder resulting from the polymerization of Hemoglobin S. Acute vaso-occlusive crisis and multiple organ damage are the most common complications of SCA. Because of its multifunctional role in inflammation, endothelial dysfunction, and fibrosis, TGF-β1 could be involved in SCA development, which may explain a variety of symptoms associated with this disease. This study aimed to investigate the role of TGF-β1 as a noninvasive biomarker for predicting the types of SCA clinical manifestations and highlights the complication frequency in this group.
Methods: The level of TGF-β1 in serum was measured using the enzyme-linked immunosorbent assay (ELISA) method in 98 SCA patients and 98 healthy individuals without any history of hemoglobinopathies, who served as the control group. Moreover, a questionnaire was completed for each patient to determine the type of clinical symptoms they experienced. Analysis of data was conducted on SPSS 26 using descriptive statistics like frequency distribution and central tendency measures.
Results: The laboratory parameters including hemoglobin, red blood cell (RBC), hematocrit (HCT), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) were lower in SCA patients compared to the control group, and white blood count (WBC), red cell distribution width-coefficient of variation (RDW-CV), platelet count, mean platelet volume (MPV), and lactate dehydrogenase (LDH) were higher in these patients. No significant correlation was observed between laboratory parameters and Transforming Growth Factor Beta 1 (TGF-β1) level (p > 0.05). The serum TGF-β1 level was higher in patients, but there was no significant correlation between TGF-β1 level and the type of clinical symptoms in these patients.
Conclusion: We observed a higher prevalence of certain complications in SCA patients in the Arab population of Khuzestan Province. There was no significant correlation between the clinical manifestation of SCA and TGF-β1.

Keywords: clinical manifestation; hematological biomarkers; sickle cell disease; transforming growth factor beta 1 (TGF‐β1)

DOI: https://doi.org/10.1002/hsr2.70960

Blood Adv. 2025 Jul 11. pii: bloodadvances.2025016368. [Epub ahead of print]

Outcomes and survival prediction in adults with sickle cell disease treated with extracorporeal membrane oxygenation.

Alison Grazioli, Michael Edward Plazak, Kate Willsey, Joseph Rabin, Raymond P Rector, Leonid Belyayev, Allison S Lankford, Thomas M Scalea, Aakash Shah, Bradley S Taylor, Mark T Gladwin.

The utility of extracorporeal membrane oxygenation (ECMO) support for adult patients with sickle cell disease (SCD) remains poorly understood. We aimed to characterize a cohort of adult individuals with SCD in the Extracorporeal Life Support Organization (ELSO) registry who underwent venoarterial (VA) or venovenous (VV) ECMO treatment, assess clinical outcomes for each modality and determine predictors of mortality. This multicenter, retrospective study evaluated in-hospital mortality and clinical outcomes such as bleeding and thrombotic events (BTE) of adult VA and VV ECMO ELSO registry patients with SCD associated ICD-9/10-CM codes. Post hoc multivariable logistic regression model was developed assessing predictors of mortality. Of 206 included patients, 126 and 80 were cannulated for VA ECMO or VV ECMO, respectively. Eighty-three patients (40.3%) were discharged alive; In-hospital survival was 25.5% and 61.1% for VA and VV ECMO, respectively (p<0.001). BTE was common during VA (45.6%) and VV (33.8%) ECMO support. There was significant increase in BTE incidence for non-survivors compared to survivors with VA ECMO (55.4% vs. 26.5%, p<0.001) and VV ECMO (58.1% vs. 18.4%, p=0.01). Male sex, increased age, pre-ECLS cardiac arrest, cannulation for eCPR, and elevated lactate were predictive of in-hospital mortality in the VA ECMO cohort. In adult patients with SCD, in-hospital survival was significantly lower with VA ECMO compared to VV ECMO. Male sex, increased age, eCPR support, elevated lactate and pre-ECLS arrest were strongest indicators of VA ECMO mortality. Bleeding and thrombotic complications have an association with in-patient mortality for those treated with ECMO.

DOI: https://doi.org/10.1182/bloodadvances.2025016368