bims-sicedi 2025-06-22 papers

Commun Med (Lond). 2025 Jun 18. 5(1): 238

Clinical manifestations of sickle cell disease in Africa and its association with foetal haemoglobin parameters.

Evans Xorse Amuzu, Florence Urio, Elliot Eli Dogbe, Peter Ponsian, Suraj Yawnumah Abubakar, Chinedu Okeke, Olasinbo Olumuyiwa Balogun, Petronilla Jean Ozumba, Alex Osei-Akoto, Vivian Paintsil, Obiageli Nnodu, Emmanuel Balandya, Julie Makani, Madu Anazoeze, Daniel Ansong, Siana Nkya.

BACKGROUND: Prevalence of sickle cell disease (SCD) across African countries ranges between 1-3% and contributes up to 7-16% of under-five mortality. In order to bridge the gap in management and cognate research, the SickleInAfrica consortium was established in 2017 to facilitate collaboration among African nations in order to establish regionally relevant healthcare standards for SCD patients. This work utilised the SickleInAfrica platform to study the levels of HbF and F cells and their relationship with sickle cell disease clinical manifestations in Ghana, Nigeria and Tanzania.
METHODS: This study enrolled 290 individuals with SCD aged five years and above who were confirmed to be at steady state and were hydroxyurea naïve. Clinical history was obtained using an interviewer-administered questionnaire. Haematological parameters were determined by an automated haematology analyser, while quantification of HbF and F cells was implemented by high-performance liquid chromatography and flow cytometry, respectively. Age-adjusted logistic regression was employed to assess the association of HbF with the clinical manifestations.
RESULTS: The most reported complication of SCD, requiring management in a hospital setting is pain crises, ranging from 66-96% with the highest in Tanzania and lowest in Ghana. HbF and F cell parameters show significant association with transfusion rates, frequency of painful crises and episodes of febrile illness.
CONCLUSION: This work highlights important differences and similarities across SCD populations in the three countries. This is important especially in development of interventions in the light of personalised medicine.

DOI: https://doi.org/10.1038/s43856-025-00954-z

Am J Hematol. 2025 Jun 20.

Impact of Duffy Status on Neutrophil Counts and Clinical Outcomes in Pediatric Patients With Sickle Cell Disease.

Yan Zheng, Jeffrey Gossett, Pei-Lin Chen, Guolian Kang, Clifford M Takemoto.

Keywords: Duffy; Duffy‐null associated neutrophil count (DANC); hydroxyurea; neutrophils; sickle cell disease

DOI: https://doi.org/10.1002/ajh.27748

Expert Rev Hematol. 2025 Jun 17.

Efficacy and safety of pyruvate kinase activator in treating hemolytic anemias: a systematic review.

Syed Hassan Ahmed, Laila Tul Qadar, Jawad Ahmed, Zohaib Yousaf, Afsana Ansari Shaik, Muhammad Sohaib Asghar.

INTRODUCTION: Pyruvate kinase (PK) is an important glycolytic enzyme responsible for erythrocytic ATP production. PK allosteric activators have been shown to increase ATP and reduce 2,3-disphosphoglycerate among red blood cells leading to improved oxygen affinity, sickling, and hemolysis. In this systematic review, we aim to evaluate the efficacy and safety of PK activators in hemolytic anemias.
METHODS: This study was conducted following the PRISMA guidelines. A literature search was conducted using relevant keywords over PubMed/Medline, Google Scholar, Cochrane Library, and clinicaltrial.gov, till 29 September 2024. Relevant data was extracted into a spreadsheet and synthesized qualitatively.
RESULTS: The literature search yielded 7,153 results, with 7 studies ultimately included in the review. These studies involved 206 patients, 166 of whom received mitapivat and the rest received placebo. Hemoglobin response was achieved by 38.0% to 80.0% of participants receiving mitapivat, with an average increase of 0.4 to 1.7 g/dL. Most studies reported improvements in bilirubin, lactate dehydrogenase, haptoglobin, and reticulocyte levels. Adverse events (AEs) were experienced by 93.2% of participants, with rates of 93.97% and 89.7% in the intervention and control groups, respectively. However, most AEs were mild and transient, and 23.4% were graded as 3 or higher.
CONCLUSIONS: In this study, PK activators, particularly mitapivat, demonstrated promising efficacy and safety profiles in managing hemolytic anemias. These agents significantly improved hemoglobin levels, markers of hemolysis, and hematopoietic response, offering a beneficial therapeutic option for various hemolytic conditions, including pyruvate kinase deficiency, sickle cell disease, and thalassemia.
REGISTRATION: A protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) before study initiation, CRD42024598980.

Keywords: Hemolytic anemia; mitapivat; pyruvate kinase; pyruvate kinase activators

DOI: https://doi.org/10.1080/17474086.2025.2522295

Paediatr Drugs. 2025 Jun 17.

Clinical Study to Evaluate the Possible Efficacy and Safety of L-Arginine in Children with Sickle Cell Disease and Increased Tricuspid Regurgitant Jet Velocity: a Randomized Controlled Trial.

Dalia A Gomaa, Sahar M El-Haggar, Mohamed R El-Shanshory, Osama El-Razaky, Dalia R El-Afify.

BACKGROUND: Pulmonary hypertension (PH) is a common chronic complication of sickle cell disease (SCD), and patients at risk for PH can be identified by measuring tricuspid regurgitant jet velocity (TRJV). We looked for the possible efficacy of L-arginine for children with SCD who have elevated TRJV.
METHODS: In total, 50 children with SCD who had TRJV higher than 2.5 m/s were randomly divided into two groups, each with 25 patients: group 1 (control group) and group 2 (treatment group). Group 2 received L-arginine at a dose of 0.1-0.2 g/kg/day for 3 months. Transthoracic echocardiography was conducted to measure TRJV at baseline and after 3 months, and blood samples were collected at baseline and after 3 months to assess serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), lactate dehydrogenase (LDH), nitric oxide (NO), L-arginine (LA), asymmetric dimethylarginine (ADMA), and LA/ADMA ratio.
RESULTS: After 3 months of treatment, the L-arginine-treated group had significantly lower TRJV levels than the control group, and compared with baseline. They also had significantly lower NT-proBNP and significantly higher NO, LA and LA/ADMA ratios than the control group and compared with baseline. No significant differences in side effects were observed between the two groups, indicating that L-arginine is safe for these patients.
CONCLUSIONS: L-arginine is associated with a reduction in TRJV, NT-proBNP, and improvements in NO biomarkers, suggesting it may be beneficial for reducing the risk of pulmonary hypertension in children with sickle cell disease.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05470998.

DOI: https://doi.org/10.1007/s40272-025-00701-w

JAMA Netw Open. 2025 Jun 02. 8(6): e2517974

Hospital Readmissions Among People With Sickle Cell Disease.

Ruchika Goel, Ping Yang, Xianming Zhu, Eshan U Patel, Elizabeth P Crowe, Herleen Rai, Evan M Bloch, Aaron A R Tobian.

Importance: While advances in the management and treatment of sickle cell disease (SCD), the most common inherited disorder in the United States, have improved outcomes, hospital readmissions remain a significant concern. Thirty-day hospital readmissions is a key quality-of-care indicator; however, there are limited contemporary nationally representative data on SCD readmissions.
Objective: To characterize national trends in SCD-related readmissions in the United States and describe factors associated with readmission among patients with SCD.
Design, Setting, and Participants: This cohort study included patients with SCD aged 18 years and older. Patients were identified in the Nationwide Readmissions Database (NRD), an all-payer database of US hospitalizations, using International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes. Data were collected from January 2016 to December 2021 and analyzed from May to September 2024.
Main Outcomes and Measures: Readmission was defined as subsequent admission within 30 days of hospitalization discharge using the Centers for Medicare & Medicaid Services methodology. The 30-day all-cause unplanned readmission risk among adults with SCD was estimated, and the trend in 30-day readmissions among adults with and without SCD was assessed by calendar year from 2016 to 2021. Survey-weighted mixed-effect Poisson regressions were used to identify factors associated with readmission.
Results: From 2016 to 2021, 140 096 807 all-cause index hospitalizations and 592 951 SCD-related index hospitalizations were analyzed. Patients with SCD had a stable readmission risk of approximately 34% (annual range, 32.6%-34.3%), significantly higher per year than the approximately 12% readmission risk among patients without SCD (annual range, 12.0%-12.2%) (P < .001). In 2021, there were 92 536 index admissions from 37 410 unique patients with SCD (median [IQR] age, 34 [26-46] years; 22 484 [60.1%] female), with 30 467 readmissions. Younger patients (aged 18-29 years) had the highest readmission risk at 35.1%. In multivariable model among patients with SCD, patients from the highest-income zip codes had lower readmission risk than those from lower-income areas (adjusted risk ratio [aRR], 0.90; 95% CI, 0.84-0.97). Admissions paid by Medicare and Medicaid were associated with higher readmission risk than private insurance (Medicare: aRR, 1.67; 95% CI, 1.56-1.78; Medicaid: aRR,1.53; 95% CI, 1.43-1.63). Vaso-occlusive crises at index admission were associated with higher readmission risk (aRR, 1.31; 95% CI, 1.25-1.37). Fewer readmissions were observed in patients receiving simple (aRR, 0.86; 95% CI, 0.82-0.91) and exchange (aRR, 0.78; 95% CI, 0.61-0.99) red blood cell transfusions.
Conclusions and Relevance: In this cohort study with nationally representative data, patients with SCD had a significantly higher readmission risk than patients without SCD. Preventative, disease-modifying, and curative interventions are needed to reduce readmission risks and improve outcomes for patients with SCD.

DOI: https://doi.org/10.1001/jamanetworkopen.2025.17974

Blood Adv. 2025 Jun 17. pii: bloodadvances.2025015947. [Epub ahead of print]

Severe Parvovirus B19 Infection in Patients with Sickle Cell Disease Hospitalized in Intensive Care Unit.

Segolene Gendreau, Louis-Marie Coupry, Pierre Cappy, Alexandra Beurton, Nicolas Verger, Anoosha Habibi, Maïté Agbakou, Sylvain Le Jeune, Laurent Argaud, Serge Barmo, Gauthier Blonz, Pierre Cougoul, Stéphanie Houcke, Antoine Lafarge, Arnaud Ly, Andréa Pastissier, Armand Mekontso Dessap, Slim Fourati, Nicolas de Prost.

Parvovirus B19 infection can lead to severe complications in patients with chronic haemolysis. The aim of this study was to describe severe Parvovirus B19 infections in adult patients with sickle cell disease (SCD). In this multicentre, retrospective, observational cohort study, adult patients with SCD admitted to intensive care units (ICUs) between 2011 and 2024 with acute Parvovirus B19 infection were included. Unsupervised analysis was performed including clinical and biological characteristics to identify clusters of patients with different outcomes. Clinical phenotypes were defined based on patient clustering. Parvovirus B19 genomes from ICU (n=15) and non-ICU control patients (n=15) admitted to the hospital during the same period were sequenced and compared. Sixty-one patients (52% female, median age: 29 years [IQR: 24;38]) from eight ICUs in France were included. Three clusters of patients were identified. From these clusters, three groups of patients with distinct clinical phenotype were identified: erythroblastopenia (n=26), bone marrow necrosis (BMN) and fat cerebral embolism syndrome (CFE) (n=17), and other vaso-occlusive manifestations (n=18). Length of stay in the ICU and hospital was longer in patients with BMN/CFE. There was no difference in Parvovirus B19 genotype or NS1 or VP1/2 amino-acid diversity between the groups. Similar results were observed between patients who were admitted to the ICU and those who were not. ICU patients with SCD and acute Parvovirus B19 infection presented three clinical phenotypes associated with different initial severity and outcome, but with similar Parvovirus B19 clades and amino-acid diversity.

DOI: https://doi.org/10.1182/bloodadvances.2025015947