bims-sicedi Biomed News
on Sickle cell disease
Issue of 2026–02–08
ten papers selected by
João Conrado Khouri dos Santos, Universidade de São Paulo
  1. Caring for People With Sickle Cell Disease in Correctional Settings.
  2. The role of hemoglobin F in sickle cell disease complications: a descriptive secondary analysis.
  3. Microfluidic capillary transit velocity as a functional measure for sickle cell disease and in vitro-derived red blood cells.
  4. Targeting PAR1 Biased Signaling with Parmodulin Reduces Thromboinflammation and Acute Lung Injury in Sickle Cell Disease.
  5. Luspatercept ameliorates disease phenotype and complications in the Townes mouse model of sickle cell disease.
  6. Cytokine and immune cell interaction in immune-inflammatory response during crisis event in sickle cell disease.
  7. Therapeutic Plasma Exchange as a Rescue Therapy in Sickle Cell Disease-Associated Fat Embolism Syndrome: Case Series and Literature Review.
  8. Increased Endothelin-1 and High-Risk APOL1 Variants Contribute to Albuminuria in Pediatric and Young Adults with Sickle Cell Anemia.
  9. Increasing daily step counts improves physical fitness, reduces pain and arterial stiffness in sickle cell patients.
  10. End-of-Life Care in Sickle Cell Disease and Transfusion-Dependent β-Thalassemia: Clinical, Psychosocial, and Ethical Considerations.
  1. J Correct Health Care. 2026 Feb 02. 10783458251413180
    Caring for People With Sickle Cell Disease in Correctional Settings.
      
    DOI:  https://doi.org/10.1177/10783458251413180
  2. Blood Vessel Thromb Hemost. 2026 Feb;3(1): 100114
    The role of hemoglobin F in sickle cell disease complications: a descriptive secondary analysis.
    Heath Aston, Elexis Price, Elena Wernecke, Emma Hazenberg, Daniel Herrera, Siera Gollan, Hongyan Xu, Girindra Raval, Abdullah Kutlar.
      Individuals with sickle cell disease (SCD), a prevalent inherited blood disorder, are at increased risk for tissue ischemia and thrombosis secondary to sickle hemoglobin polymerization. Fetal hemoglobin (HbF) protects against the vaso-occlusive nature of sickled erythrocytes. Our study aims to investigate the association between HbF level and various SCD complications. The study used a descriptive and cross-sectional design to analyze existing, secondary medical record data of 496 patients with SCD who received care from the Center for Blood Disorders in Augusta, Georgia. Of these, only patients with HbSS and an HbSβ0 thalassemia (n = 273) were included in the analysis. Data abstraction included history of thrombotic event (TE) and HbF values closest to the TE, along with presence of SCD clinical complications, use of anticoagulation medications, specific laboratory values, and Hb electrophoresis. These patients were reflective of the greater population of patients with SCD in that they had similar rates of complications such as avascular necrosis and sickle cell retinopathy compared with nationally reported data. We found a significant association between incidence of thrombosis and higher HbF levels (P = .034). The presence of HbF was also found to influence the incidence of complications, including avascular necrosis and pulmonary hypertension. When stratified into quantiles, there was a relationship between HbF and incidence of AVN in male patients (P = .038). Further research is warranted to investigate whether other treatments for SCD produce similar results and whether this effect is representative of other large patient populations with SCD.
    DOI:  https://doi.org/10.1016/j.bvth.2025.100114
  3. Lab Chip. 2026 Feb 03.
    Microfluidic capillary transit velocity as a functional measure for sickle cell disease and in vitro-derived red blood cells.
    Solomon Oshabaheebwa, Utku Goreke, Yuxuan Du, Christopher L Wirth, Zoe Sekyonda, Bryan L Benson, Payam Fadaei, Yusang B Ley, Nathan M Perez, Petros Giannikopoulos, David N Nguyen, Michael A Suster, Pedram Mohseni, Umut A Gurkan.
      Emerging therapies in sickle cell disease (SCD) aim to restore healthy red blood cell (RBC) function, but they often yield heterogeneous cellular responses. There are no proven techniques to evaluate restored rheological functionality and heterogeneity in these RBCs. We present a biomimetic microcapillary network, high-speed imaging, and computational algorithms to analyze RBC capillary velocity profiles of the entire sample population at single-cell resolution. Using peripheral RBCs from SCD patients and healthy donors, we showed that RBC capillary transit velocity correlated with cell shape, hydrodynamic adaptability, and elongation index. Healthy RBCs exhibited a velocity distribution skewed toward higher values, whereas RBCs from individuals with SCD showed a shift toward lower velocities. SCD samples had a greater fraction of slow RBCs than healthy controls (42.1% ± 12.0% vs. 19.0% ± 4.9%, p < 0.0001). We tested mixtures of healthy and SCD RBCs to simulate heterogeneous therapeutic effects and demonstrated that the assay was sensitive to small fractions of abnormal RBCs. The slow RBC fraction emerged as a potential biomarker associated with SCD disease severity. This fraction significantly increased under hypoxia showing sensitivity to hypoxia-induced sickling. Finally, we assessed in vitro-derived RBCs and observed distinct velocity profiles for nucleated and enucleated cells. Processing methods to enrich enucleated RBCs improved the velocity profile, producing a distribution that was more comparable to that of peripheral RBCs. This platform's ability to assess individual RBCs and generate a velocity profile from a small number of cells makes it well suited for evaluating the rheological properties of in vitro-derived RBCs.
    DOI:  https://doi.org/10.1039/d5lc00769k
  4. Blood Adv. 2026 Feb 03. pii: bloodadvances.2025017522. [Epub ahead of print]
    Targeting PAR1 Biased Signaling with Parmodulin Reduces Thromboinflammation and Acute Lung Injury in Sickle Cell Disease.
    Nirupama Ramadas, Kailyn Lowder, Joshua Dutton, Rebecca Claire Kazen, Rani S Sellers, Jacob T DeRousse, Christopher J Dockendorff, Erica M Sparkenbaugh.
      Protease activated receptor 1 (PAR1) is expressed by numerous cell types, including endothelial. Thrombin cleaves PAR1 at Arg41 and activates pro-inflammatory and barrier disruptive signaling. Alternatively, PAR1 is cleaved at Arg46 by activated protein C (APC) bound to endothelial protein c receptor (ECPR), inducing anti-inflammatory and barrier protective signaling. In sickle cell disease (SCD), we showed that thrombin-PAR1 signaling contributes to vascular stasis, and more recently that PAR1-R41 biased signaling enhances inflammation, whereas PAR1-R46 signaling reduces thrombo-inflammation. We hypothesized that ECPR-PAR1-R46 biased signaling protects sickle mice from thrombo-inflammation. To test this hypothesis, Townes sickle mice were treated with parmodulin (parmodulin 2 (PM2, aka ML161), or NRD-21) to promote protective, anti-inflammatory PAR1-biased signaling. We found that PM2 significantly attenuated thrombin generation, inflammation, endothelial activation, and protected sickle mice from a model of lethal acute chest syndrome. These results suggest that utilizing PM2 to block thrombin-PAR1 signaling while inducing APC-like signaling can promote cytoprotective, anti-inflammatory effects in mouse models of SCD.
    DOI:  https://doi.org/10.1182/bloodadvances.2025017522
  5. J Clin Invest. 2026 Feb 02. pii: e197706. [Epub ahead of print]136(3):
    Luspatercept ameliorates disease phenotype and complications in the Townes mouse model of sickle cell disease.
    Maiko Sezaki, Tian Li, Mingzhe Pan, Zhihong Wang, Jie Bai, Justin G Horowitz, Julia Z Xu, Gang Huang.
      Preclinical data demonstrating that luspatercept mitigates vaso-occlusive and anemia-related complications in the Townes sickle cell model provide a strong rationale for its evaluation in SCD patients.
    Keywords:  Hematology; Hematopoietic stem cells; Immunology
    DOI:  https://doi.org/10.1172/JCI197706
  6. Afr Health Sci. 2025 Mar;25(1): 474-497
    Cytokine and immune cell interaction in immune-inflammatory response during crisis event in sickle cell disease.
    Suprava Patel, Saurav Nayak, Diksha Chandrakar, Preetam N Wasnik, Tushar B Jagzape, Eli Mohapatra, Rachita Nanda, Seema Shah.
       Background: The present study focused on evaluating serum cytokines in SCD cases and understanding these mediators' interplay with immune cells and their impact on disease severity score(DSscore).
    Methods: The study population of eighty-eight participants comprised twenty-one SCD cases with DSscore>5, thirty-seven SCD cases with DSscore≤5, and thirty control group. Blood samples were analyzed for T cell markers by flowcytometry and serum IL10, TNFα, IFNγ, and glutathione.
    Results: Serum IFNγ and IL10 levels were significantly higher in cases than control(p<0.05). The median(IQR) TNFα, 100.51(66.8) was higher in cases DSscore>5 than those with DSscore≤5(p=0.04). Both cases showed a significant rise in IFNγ compared to the control group(p<0.05). Similarly, median(IQR) IL10, 7.9(13.3) was elevated in cases DSscore>5(p=0.001) than control group. IL10 recorded a significant linear relationship with Tc-exhausted (CD8+CD279+) cells(r= 0.327, p=0.012) and Th-exhausted (CD4+CD279+) cells(r=0.265, p=0.045). A linear association(r=0.292, p=0.026) was observed between IFNγ and Tc Naive/Effector cell ratio (CD8+NECR). Similarly, TNFα was positively associated with the total T cell Naive/Effector cell ratio (TNECR) (r=0.307, p=0.019). Serum glutathione levels correlatedh exhausted (CD4+CD279+) cell (r=0.393, p=0.002) and IL10 (r=0.589, p<0.001). Conclusion: Cytokine profiling in SCD patients might provide insight into the underlying clinical course and vulnerability toward crisis events.
    Keywords:  IFNγ; IL10; TNFα
    DOI:  https://doi.org/10.4314/ahs.v25i1.36
  7. Hemoglobin. 2026 Feb 03. 1-8
    Therapeutic Plasma Exchange as a Rescue Therapy in Sickle Cell Disease-Associated Fat Embolism Syndrome: Case Series and Literature Review.
    Abdulmohsen K Aljishi, Fatimah A Alrabia, Abdullah M Al Abbas, Mona M Alfaraj, Fadhel A Alomar, Salah Abohelaika.
      Fat embolism syndrome (FES) in sickle cell disease (SCD) remains a significant diagnostic and therapeutic challenge, often associated with high morbidity and mortality. While red blood cell exchange (RCE) is the standard first-line therapy, some cases continue to deteriorate despite aggressive management. Emerging evidence suggests that therapeutic plasma exchange (TPE) may serve as valuable salvage therapy, potentially improving survival in refractory cases. We present two cases of FES in SCD, both marked by an attack of profound hypotension and multiorgan dysfunction, yet with distinct trajectories and responses to therapy. The first case involved a 34-year-old female with FES refractory to conventional treatment, including RCE. A single session of TPE led to rapid clinical stabilization and recovery. The second case described a 28-year-old female with a more severe disease course, requiring five cycles of combined RCE and TPE before achieving clinical improvement and recovery. These cases underscore the potential role of TPE as an adjunct to RCE in managing FES in SCD and highlight the need for further research to establish its efficacy in this critical setting.
    Keywords:  Sickle cell disease; blood transfusion; fat embolism syndrome; multiorgan dysfunction; therapeutic plasma exchange
    DOI:  https://doi.org/10.1080/03630269.2026.2625352
  8. Clin J Am Soc Nephrol. 2026 Jan 30.
    Increased Endothelin-1 and High-Risk APOL1 Variants Contribute to Albuminuria in Pediatric and Young Adults with Sickle Cell Anemia.
    Malgorzata Kasztan, Guolian Kang, Davide Botta, David M Pollock, Sara Rashkin, Rima Zahr, Jeffrey Lebensburger.
      
    DOI:  https://doi.org/10.2215/CJN.0000000993
  9. Haematologica. 2026 Feb 05.
    Increasing daily step counts improves physical fitness, reduces pain and arterial stiffness in sickle cell patients.
    Franciele De Lima, Mor Diaw, Elie Nader, Romain Carin, Marie Ducray, Mame Saloum Coly, Keyne Charlot, Muriel Marano, Mathieu Gallou-Guyot, Saliou Diop, Motohiko Miyachi, Tsukasa Yoshida, Moussa Seck, Abdoulaye Samb, Brigitte Ranque, Julien Tripette, Philippe Connes.
      Patients with sickle cell anemia (SCA) have long been discouraged from physical activity (PA). The aim of the present study was to assess the impact of increasing daily step counts on physical fitness, pain and vascular function in patients with SCA. Thirty-eight patients with SCA were recruited and equipped with a Fitbit wrist-worn accelerometer-based PA tracker for 5 weeks to objectively quantify their baseline daily step counts. Patients were then randomly assigned to one of the three groups: 1) control group: no specific information regarding PA was given for 8 weeks (N=12); 2) PA1 group: daily step counts increased by 25% of baseline for 8 weeks (N=12); 3) PA2 group: daily step counts increased by 25% for 4 weeks, then by 50% for 4 additional weeks (N = 14). Pain intensity and frequency decreased after the intervention in the PA1 and PA2 groups. In addition, patients from these two groups increased the distance walked in 6 minutes. Arterial stiffness decreased in both PA1 and PA2 groups, without any change in the autonomic nervous system activity. Several inflammatory markers slightly decreased in the PA2 group. Incubation of cultured endothelial cells with patient plasma showed a decrease in the percentage of ICAM-1 positive cells in the PA2 group. This study is the first to show that increasing daily PA by a simple way (i.e., increasing daily step count of 25-50%) for 8 weeks is sufficient to decrease pain, and improve physical condition and vascular function of patients with SCA.
    DOI:  https://doi.org/10.3324/haematol.2025.300290
  10. Mediterr J Hematol Infect Dis. 2026 ;18(1): e2026015
    End-of-Life Care in Sickle Cell Disease and Transfusion-Dependent β-Thalassemia: Clinical, Psychosocial, and Ethical Considerations.
    Sophia Delicou, Katerina Xydaki, Maria Moraki, Theodoros Aforozis.
      Sickle cell disease (SCD) and transfusion-dependent β-thalassemia are no longer pediatric death sentences. With newborn screening, transfusions, and chelation therapy, patients now survive into their 4th-6th decade. Yet as they age, they face mounting complications -pain that never truly resolves, organs failing one by one, and profound isolation. Ironically, palliative care remains scarce despite the clinical complexity. This narrative review examines end-of-life care in these hemoglobinopathies, focusing on pain management, ethical tensions, and the psychosocial needs that intensify as death approaches. We reviewed literature from 2020 to 2025, international guidelines, and European frameworks. The evidence is clear: terminal SCD involves unpredictable crises and intractable pain; β-thalassemia brings slow cardiac decline and iron-laden organ failure. Both demand early palliative integration, yet both are drastically undertreated. Cultural beliefs heavily shape how families accept or reject end-of-life discussions. Disparities in opioid access, lack of disease-specific referral criteria, and absence of flexible hospice models create barriers that disproportionately harm marginalized patients. We conclude that hemoglobinopathy patients deserve the same anticipatory, culturally informed, multidisciplinary palliative care that we increasingly offer to cancer patients. Health systems must establish referral pathways specific to these diseases, permit palliative transfusions in hospice when appropriate, ensure equitable opioid access, and embed psychosocial support in hemoglobinopathy centers.
    Keywords:  Cultural competence; End-of-life; Ethical decision-making; Hospice care; Integrated care models; Pain management; Palliative care; Sickle cell disease; β-thalassemia
    DOI:  https://doi.org/10.4084/MJHID.2026.015
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