bims-sicedi 2025-10-12 papers

bims-sicedi

Biomed News

on Sickle cell disease

Issue of 2025–10–12
sixteen papers selected by
João Conrado Khouri dos Santos, Universidade de São Paulo

Targeting PIEZO1-TMEM16F Coupling to Mitigate Sickle Cell Disease Complications.
Mitochondrial Retention and Autophagy Dysregulation Drive Oxidative Stress in Sickle Cell Disease Erythrocytes.
Granulocyte colony-stimulating factor may improve engraftment in adults with sickle cell disease undergoing non-myeloablative haematopoietic stem cell transplantation.
UHRF2 as a genetic correlate of hospitalization in sickle cell disease.
Early-life clinical and hematological profiles: a comparative study of children with and without sickle cell disease in the first three years of life.
Clinical and haematological features of hyperhaemolysis in sickle cell disease: A case series from two tertiary care centres.
Feasibility, safety and efficacy of intranasal fentanyl in the treatment of acute pain episodes among adults with sickle cell disease: A retrospective single-centre study.
Strategies to mitigate transfusion-associated red blood cell alloimmunization in sickle cell disease: A retrospective analysis.
The Economic and Clinical Impact of Recurring Automated Red Blood Cell Exchange to Manage Sickle Cell Disease in the UK.
10-Year Longitudinal Study Clarifies Impact of Hemolysis and Pulmonary Hypertension on Patients with Sickle Cell Anemia.
Use of Incentive Spirometry to Prevent Acute Chest Syndrome (ACS) in Patients With Sickle Cell Disease (SCD): A Systematic Review.
Growth measurements in Ugandan children with sickle cell anaemia from a hydroxyurea (hydroxycarbamide) treatment trial relative to unaffected sibling controls.
Emergency department utilization patterns in adults living with sickle cell disease.
Primary and Secondary Stroke Prophylaxis in Children with Sickle Cell Anemia: A Meta-Analysis.
Tocilizumab provides a potential therapeutic option for the management of hyperhaemolysis syndrome in sickle cell disease: A case series and brief narrative overview of the literature.
Erythrocyte Alloimmunization and Transfusion Strategies in Sickle Cell Disease: A Single-Center Analysis.

Am J Hematol. 2025 Oct 08.

Targeting PIEZO1-TMEM16F Coupling to Mitigate Sickle Cell Disease Complications.

Pengfei Liang, Yui-Chun S Wan, Ke Z Shan, Ryan Chou, Yang Zhang, Martha Delahunty, Sanjay Khandelwal, Samuel J Francis, Gowthami M Arepally, Marilyn J Telen, Huanghe Yang.

A deeper understanding of sickle cell disease (SCD) pathophysiology is critical for identifying novel therapeutic targets. A hallmark of SCD is abnormal phosphatidylserine (PS) exposure on sickle red blood cells (RBCs), which contributes to anemia, thrombosis, and vaso-occlusive crises (VOC). However, the mechanisms underlying this excessive PS exposure remain unclear. Here, we identify TMEM16F, a Ca2+-activated lipid scramblase, as a key mediator of PS exposure downstream of Ca2+ influx through the mechanosensitive channel PIEZO1 in sickle RBCs. Electrophysiology, imaging, and flow cytometry reveal that deoxygenation-induced sickling activates PIEZO1, triggering Ca2+ entry, TMEM16F activation, and PS exposure. This cascade promotes PS+ microparticle release, thrombin generation, and RBC adhesion to endothelial cells. Notably, partial PIEZO1 inhibition with benzbromarone, an anti-gout drug, suppresses these effects. Our findings define a previously unrecognized mechanotransduction pathway in sickle RBCs and propose a unique therapeutic strategy to mitigate hypercoagulability and vaso-occlusion associated with SCD.

DOI: https://doi.org/10.1002/ajh.70086
Exp Hematol. 2025 Oct 02. pii: S0301-472X(25)00558-2. [Epub ahead of print] 105269

Mitochondrial Retention and Autophagy Dysregulation Drive Oxidative Stress in Sickle Cell Disease Erythrocytes.

Jagadeesh Ramasamy, Prasanth Kumar Punathil Kannan, Sugasini Dhavamani, Savitha Palanimuthu, Robert Molokie, Angela Rivers.

  Sickle cell disease (SCD) is an inherited blood disorder caused by a mutation in the beta-globin gene, leading to hemoglobin polymerization under low oxygen conditions. This results in sickle-shaped red blood cells (Erythrocytes), hemolysis, severe acute and chronic pain, and shortened erythrocyte lifespan. The severity of disease in SCD is linked to the type of hemoglobin mutation, with HbSS causing more frequent and severe than HbSC. We previously identified mitochondrial retention and excessive reactive oxygen species (ROS) production in SCD erythrocytes. Here, we report that SCD patients with the HbSS exhibit significantly higher erythrocyte mitochondrial retention and ROS levels than those with the HbSC. Mitochondrial retention positively correlates with serum bilirubin and LDH, particularly in hydroxyurea-naïve patients. Gene expression analysis using a human autophagy array revealed upregulation of SNCA, GABARAP, GABRAPL2, MAP1LC3B, and CTSB in erythrocyte precursor cells from SCD patients experiencing severe pain. Immunoblot analyses further confirmed accumulation of GABARAP, GABARAPL1, GABARAPL2, cathepsin B, and synuclein-alpha in circulating erythrocytes and plasma from SCD patients compared to controls. Our findings suggest a potential link between dysregulated autophagy proteins and erythrocyte mitochondrial retention in SCD patients, opening new avenues for therapeutic interventions targeting these proteins to mitigate SCD pathogenesis. TEASER ABSTRACT: Sickle cell disease (SCD) causes painful crises due to hemoglobin mutations, with HbSS patients experiencing more severe symptoms than HbSC. We show that HbSS erythrocytes retain more mitochondria and produce higher ROS levels, correlating with bilirubin and LDH, especially in hydroxyurea-naïve individuals. Autophagy-related genes and proteins SNCA, GABARAPs, CTSB are upregulated in erythrocyte precursors and plasma of SCD patients with severe pain. These findings suggest a potential link between dysregulated autophagy proteins and mitochondrial retention in SCD patients, opening new avenues for therapeutic interventions.

Keywords:  Autophagy; Cathepsin-B; Gabarap; Hemolysis; Mitochondria; Pain; Reactive oxygen species; Sickle cell disease; Synuclein-alpha

DOI:  https://doi.org/10.1016/j.exphem.2025.105269
Br J Haematol. 2025 Oct;207(4): 1690-1693

Granulocyte colony-stimulating factor may improve engraftment in adults with sickle cell disease undergoing non-myeloablative haematopoietic stem cell transplantation.

Shaoshi Zhu, Lucas Maahs, Karen Sweiss, Sally A Campbell-Lee, Nadim Mahmud, Victor R Gordeuk, Damiano Rondelli, Santosh L Saraf.



Keywords:  G‐CSF; engraftment; haematopoietic stem cell transplantation; non‐myeloablative; sickle cell disease

DOI:  https://doi.org/10.1111/bjh.70093
Br J Haematol. 2025 Oct 05.

UHRF2 as a genetic correlate of hospitalization in sickle cell disease.

REDS‐III Brazil SCD Cohort study and the TOPMed consortium



Keywords:  genetics; gwas; sickle cell disease

DOI:  https://doi.org/10.1111/bjh.70172
Ann Hematol. 2025 Oct 09.

Early-life clinical and hematological profiles: a comparative study of children with and without sickle cell disease in the first three years of life.

Siana Nkya, Isihaka Mahawi, Rehema Shungu, Collin Nzunda, Frida Kaywanga, David Solomon, Theogloria Kerrety, Emmanuel Josephat, Heavenlight Christopher, Doreen Ngowi, Julieth Johansen, Florence Urio, Josephine Mgaya, Upendo Masamu, Clara Chamba, Raphael Sangeda, Fadya Hashim, Emmanuela Ambroise, Lulu Chirande, Agnes Jonathan, Emmanuel Balandya, Solomon Ofori Acquah, Julie Makani.

  Sickle cell disease (SCD) has been associated with significant morbidity and mortality, particularly in early childhood. Understanding the hematological and clinical outcomes during the early years of life is crucial for guiding interventions to improve care for affected populations. This study investigates the relationship between fetal hemoglobin (HbF) levels, hematological profiles, and clinical outcomes in children with SCD, from birth to three years of age. By comparing children with and without SCD, the study aimed to identify trends in disease progression and highlight the need for early screening and intervention. This longitudinal study recruited and followed children aged 0-3 years. Clinical complaints and hematological parameters were recorded at each visit. Statistical analyses explored associations between HbF levels, hematological parameters, and clinical outcomes in children with SCD. 414 children were recruited, 35.5% with SCD and 64.5% without SCD. Children with SCD experienced a higher frequency of clinical complaints. The hospital admission rate was higher among children with SCD (19.6%) compared to those without (1.7%) (p < 0.007), with severe anemia being the leading cause of admission (56.3%). At birth, children with SCD had higher HbF levels (72.87%) that declined over time. The rate of decline correlated with an increased frequency of clinical events in children with SCD. Additionally, children with SCD had lower red cell indices, and higher reticulocyte count as well as white blood cell count. The results emphasize the need for early intervention and continuous monitoring to manage the disease effectively. Further research is recommended to explore the impact of different interventions on improving the quality of life and survival rates in children with SCD.

Keywords:  Clinical profile; Fetal hemoglobin; Hematological profile; Sickle cell disease

DOI:  https://doi.org/10.1007/s00277-025-06479-8
Br J Haematol. 2025 Oct 06.

Clinical and haematological features of hyperhaemolysis in sickle cell disease: A case series from two tertiary care centres.

Jaehyup Kim, James D Burner, Christopher Webb, Ravi Sarode, Brian D Adkins, Margaret Kypreos, Ibrahim F Ibrahim, Yu-Min Shen, Sean G Yates.



Keywords:  hyperhaemolysis; sickle cell disease

DOI:  https://doi.org/10.1111/bjh.70191
Br J Haematol. 2025 Oct;207(4): 1713-1715

Feasibility, safety and efficacy of intranasal fentanyl in the treatment of acute pain episodes among adults with sickle cell disease: A retrospective single-centre study.

Lauren Arena, Justine Munger, Chloé Trudeau, Jade Bergeron, Bernard Lemieux, Jules M Ross, Nazila Bettache, Denis Soulières, Stéphanie Forté.



Keywords:  clinical haematology; clinical research; haemoglobin disorders; haemoglobinopathies; sickle cell disease

DOI:  https://doi.org/10.1111/bjh.70000
Transfusion. 2025 Oct 09.

Strategies to mitigate transfusion-associated red blood cell alloimmunization in sickle cell disease: A retrospective analysis.

Elizabeth P Crowe, Chinelo P Onyenekwu, Jordan Ippolito, Xinyi Feng, Heather Smetana, Ruchika Goel, Jeremy W Jacobs, Paul M Ness, David Daniel, Herleen Rai, Aaron A R Tobian, Kathy Haddaway, Evan M Bloch.

   BACKGROUND: The American Society of Hematology (ASH) recommends prophylactic limited red blood cell (RBC) antigen matching for C, E, and K for patients with sickle cell disease (SCD). At our institution, reflexive extended antigen matching is employed: no antigen matching is undertaken initially; in the event of RBC alloimmunization, extended antigen matching (C/c, E/e, K, Fya/Fyb, Jka/Jkb, S/s) is performed prospectively.
STUDY DESIGN AND METHODS: We compared alloimmunization rates and costs of reflexive extended antigen matching with other RBC antigen-matching strategies. A 5-year retrospective review was conducted of all patients with SCD, who were transfused during the study period and lacked prior immunization. Age, sex, ABO/Rh type, number of transfused units of RBCs, antibody history, and transfusion reactions were assessed. The alloimmunization rate was defined as the number of new alloantibodies per 100 units of transfused RBCs. Costs were estimated for reflexive extended antigen matching, limited antigen matching, and extended antigen matching.
RESULTS: Of 805 patients, 325 (40.4%) met inclusion criteria. Fifty (50/325, 15.4%) patients developed a positive antibody-detection test after transfusing a median of 9 (interquartile range: 3-14) units (alloimmunization rate 0.29 per 100 RBCs); anti-C, E, and K were leading alloantibodies. Seven (7/50, 14.0%) responders developed additional antibodies. Two delayed hemolytic transfusion reactions (DHTRs) were reported. Reflexive extended antigen-matching cost $4,619,133 over the 5-year period; projected costs of prophylactic limited and extended antigen matching were $9,578,253 (+107%) and $14,537,373 (+215%), respectively.
DISCUSSION: Acknowledging the limitation of excluding some responders, the rates of alloimmunization and DHTRs, and comparatively low costs suggest that reflexive extended antigen matching is viable for selected settings.

Keywords:  alloimmunization; anemia; cost–benefit analysis; erythrocyte transfusion; sickle cell

DOI:  https://doi.org/10.1111/trf.18412
Pharmacoecon Open. 2025 Oct 08.

The Economic and Clinical Impact of Recurring Automated Red Blood Cell Exchange to Manage Sickle Cell Disease in the UK.

Sarah M Medland, Jamie Bainbridge, Matthew Cawson, Stuart J Mealing, Anna Yudina, Isabel Eastwood, Arne de Kreuk, Martin Besser, Eva Tsouana.

BACKGROUND/OBJECTIVE: Sickle cell disease (SCD) is a group of inherited health conditions affecting 7.74 million people worldwide. Regular automated red blood cell exchange (aRBCX) transfusions have been shown to improve control and management of SCD compared with manual RBCX (mRBCX). The aim of this study was to estimate the lifetime clinical and economic impact of aRBCX versus mRBCX in two United Kingdom-based populations with SCD (paediatrics initiated aged 5 years and adults initiated aged 38 years) that were clinically indicated for chronic disease-modifying transfusions (DMTs).
METHODS: An individual patient-level simulation model was developed to estimate lifetime quality-adjusted life years (QALYs) and healthcare costs. DMT administration programmes aligned with recommended treatment schedules. Monte Carlo methods determined baseline characteristics and clinical event occurrence. Pragmatic review findings and expert opinion informed model parameters and assumptions. Second-order probabilistic sensitivity analysis (PSA) was performed for 1000 individuals' lifetimes over 500 iterations.
RESULTS: Per individual, aRBCX reduced acute clinical events by 19% in both populations versus mRBCX. The time spent receiving chelation therapy reduced by 63 and 32 months for paediatric-initiated and adult-initiated individuals, respectively. Total lifetime DMT costs were reduced by £71,217 and £30,740 for paediatric-initiated and adult-initiated individuals, respectively. Overall, aRBCX increased QALYs and reduced costs by 0.29 and £112,811 in paediatric-initiated individuals and 0.24 and £61,895 in adult-initiated individuals. aRBCX was cost-effective in 100% of PSA iterations for both populations.
CONCLUSION: aRBCX shows potential to improve health outcomes and reduce healthcare costs for individuals with SCD initiating a chronic DMT programme.

DOI: https://doi.org/10.1007/s41669-025-00605-y
Am J Respir Crit Care Med. 2025 Oct 10.

10-Year Longitudinal Study Clarifies Impact of Hemolysis and Pulmonary Hypertension on Patients with Sickle Cell Anemia.

Mark T Gladwin, Gregory J Kato, Roberto F Machado.

DOI: https://doi.org/10.1164/rccm.202509-2289ED
Cureus. 2025 Sep;17(9): e91462

Use of Incentive Spirometry to Prevent Acute Chest Syndrome (ACS) in Patients With Sickle Cell Disease (SCD): A Systematic Review.

Tasneem Elkanzi, Ghadeer MohamedTaha, Georgia Papageorgiou.

  Sickle cell disease (SCD) is a genetic hematological disorder that causes the production of sickle-shaped red blood cells. These abnormal cells reduce the oxygen-carrying ability around the body and obstruct blood flow, potentially resulting in devastating complications such as acute chest syndrome (ACS). The objective of this systematic review is to assess whether incentive spirometry is effective in reducing the incidence of ACS in patients with SCD. This review searched databases, including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) up to August 17, 2025. Randomized controlled trials (RCTs) that used incentive spirometry in patients with SCD were included in the review. Inclusion criteria for this review include patients diagnosed with SCD who have received incentive spirometry, with outcomes compared against standard prevention for ACS or other alternative interventions aimed at preventing or managing lung pathology. Studies must report on at least one of the following outcomes: incidence of ACS, pulmonary function, hospital stay duration, hospitalization rates, or adverse effects. This study found that three RCTs (29 patients, 38 patients, and 20 patients with a total of 124 hospitalizations) were included in this review. Two studies compared incentive spirometry to standard care, while only one compared incentive spirometry to positive expiratory pressure (PEP). A meta-analysis was conducted between two studies, with one trial suggesting that incentive spirometry successfully reduced the incidence of ACS and the other trial suggesting that it could not successfully reduce it. A meta-analysis of both studies found that incentive spirometry did not successfully reduce the incidence of ACS in patients with SCD (RR=0.51; 95% CI (0.21, 1.33)). The quality of this evidence was very low, due to the wide confidence interval, high risk of bias, and substantial heterogeneity. This review concluded that incentive spirometry could not successfully reduce the incidence of ACS in patients with SCD. Limitations of the studies used included small sample sizes and heterogeneity between study populations (i.e., children vs. adults). Therefore, further research is required to assess this, including larger, well-designed RCTs to be conducted focusing on core outcome sets (COS).

Keywords:  acute chest syndrome (acs); incentive spirometer; positive expiratory pressure; sickle cell anemia; vaso-occlusive crisis

DOI:  https://doi.org/10.7759/cureus.91462
Br J Haematol. 2025 Oct 06.

Growth measurements in Ugandan children with sickle cell anaemia from a hydroxyurea (hydroxycarbamide) treatment trial relative to unaffected sibling controls.

Dennis Kalibbala, Vincent Mboizi, Grace Nambatya, Susan Murungi, Joan Ashaba, Catherine Nabaggala, Lynnth Turyagyenda, Deogratias Munube, Phillip Kasirye, Bill Wambaka, Amiirah Mpungu, John M Ssenkusu, Ruth Namazzi, Paul Bangirana, Robert O Opoka, Ezekiel Mupere, Richard Idro, Nancy S Green.

  Children with sickle cell anaemia (SCA) in sub-Saharan Africa (SSA) frequently experience impaired growth. Hydroxyurea (hydroxycarbamide) improves growth in higher resourced countries, but its effects on growth and body composition have not been evaluated in SSA. In an open-label, single-arm, 30-month dose-escalated hydroxyurea trial in Ugandan children aged 3 to <10 years (N = 264, mean age 5.6 ± 1.7 years), participant anthropometrics were compared to non-SCA sibling controls using global age- and sex-normalized z-scores. Body composition was determined using bioelectrical impedance analysis (BIA), comparing their z-scores to those generated from the controls (N = 110). Prospectively, SCA growth parameters on hydroxyurea paralleled and correlated with haemoglobin levels but remained lower than controls for weight, height and body mass index for age. Notably, growth of the SCA participants enrolled at ages 3 to <5 years did not differ from controls; instead, all group differences were attributable to those enrolled at ages 5 to <10. Further analyses revealed that growth trajectories of SCA age-dependent weight and height improved from being significantly lower than controls at trial entry to similarity at completion. Fat-free mass improved, although it and the fat mass both remained lower than that of the controls. Findings suggest that hydroxyurea promotes healthier growth and may improve body composition in children with SCA in SSA; earlier treatment initiation had a greater impact.

Keywords:  body composition; children; growth; hydroxyurea; sickle cell anaemia

DOI:  https://doi.org/10.1111/bjh.70164
Br J Haematol. 2025 Oct 07.

Emergency department utilization patterns in adults living with sickle cell disease.

Jean-Simon Rech, Aline Santin, François Lionnet, Sarah Mattioni, Evelyne Dubreucq Guerif, Olivier Steichen, Pierre Yves Boëlle.

  Most adults with sickle cell disease (SCD) attend the emergency department (ED), with significant interindividual and temporal variability. To identify the patterns of ED use, we analysed data from adults with SCD followed at a French reference centre who had ≥1 ED visit between 1 October 2013 and 31 December 2019. We used a survival model to estimate the cumulative risk of ED visits and its variability over time and applied clustering methods on these two dimensions to identify typical patterns of ED utilization. Among 656 adults (9080 ED visits), two clusters emerged: a low-use group with 529 individuals (81%) and 2924 ED visits (32%) and a high-use group with 127 individuals (19%) and 6156 ED visits (68%). All high-use group members experienced ED visits in bursts, defined as at least three visits within 3 months and at least three times more than during the previous 3 months. Bursts were uncommon in the low-use group (5% of individuals). Among individuals experiencing bursts, two ED visits less than a month apart increased the risk of another ED visit within the next month (adjusted HR 3.51 [95% CI 2.95-4.16]). Understanding factors triggering bursts of ED visits in adults with SCD may enable targeted interventions.

Keywords:  cluster analysis; facilities and services utilization; patient‐specific modelling; process assessment (health care); sickle cell disease

DOI:  https://doi.org/10.1111/bjh.70190
Blood Adv. 2025 Oct 10. pii: bloodadvances.2023012544. [Epub ahead of print]

Primary and Secondary Stroke Prophylaxis in Children with Sickle Cell Anemia: A Meta-Analysis.

Hemalatha G Rangarajan, Jose A Mejias, Alison Paige Gehred, Mark J Rodeghier, Michael R DeBaun.

We conducted a pooled analysis to evaluate the effectiveness of hydroxyurea (HU), chronic blood transfusions (CBT), myeloablative allogeneic hematopoietic stem cell transplants (HCT) with a matched related donor, and revascularization surgery (RVS) in children with sickle cell anemia (SCA). We compared the interventions with no therapy for primary and secondary stroke prevention. The Medline and EMBASE databases were searched for articles that included six or more patients published before January 2025. Four reviewers reviewed all studies to arrive at a consensus assessment. The stroke rates for primary stroke prevention in children with transcranial Doppler measurement > 200 cm/sec were per 100 person-years: no therapy, 10.7; after initial HU, 1.0; after initial CBT, 1.0. The stroke recurrence rates for secondary stroke prevention per 100 person-years were 19.6 after no therapy, 3.5 after initial HU, 2.7 after initial CBT, 1.0 after HCT, and 3.3 after RVS. Neither the HCT nor the RVS study adjusted for time-dependent stroke recurrence rate, resulting in an overestimation of their therapeutic benefit compared to the stroke recurrence rates before the intervention. In low-middle-income countries (LMICs), where approximately 99% of all children with SCA are born, the stroke recurrence rate in untreated children in the first year was 36.4 to 51.4 strokes per 100 person-years, in two studies; in the only randomized controlled trial of HU, 38% of children died within the first year. For children in LMICs where local hydroxyurea costs < $0.20 per day, HU is a practical, inexpensive option for primary and secondary stroke prevention.

DOI: https://doi.org/10.1182/bloodadvances.2023012544
Transfus Med. 2025 Oct 09.

Tocilizumab provides a potential therapeutic option for the management of hyperhaemolysis syndrome in sickle cell disease: A case series and brief narrative overview of the literature.

S Wolf, B Singh, A Zaidi, P Greaves, F Oyesanya, S Bennett, B Kaya, F Barroso, P Telfer.

   BACKGROUND AND OBJECTIVES: Hyperhaemolysis syndrome is a life-threatening complication of transfusion, potentially triggered by macrophage activation, with limited treatment options. Tocilizumab, an anti-IL6 monoclonal antibody, has mechanistic rationale for use and has been shown to be effective in a small number of cases. In this paper, we review four cases of hyperhaemolysis treated with tocilizumab in the context of the existing literature.
MATERIALS AND METHODS: Cases of use of tocilizumab in hyperhaemolysis were identified from two large specialist haemoglobinopathy centres between the period January 2021 and March 2025. Clinical and laboratory data were collected.
RESULTS: Four cases of hyperhaemolysis treated with IVIG, steroids and tocilizumab were reported. In all cases, haemolysis responded rapidly to tocilizumab therapy. Two patients subsequently received RBC transfusions without haemolysis; two patients died from causes unrelated to haemolysis.
CONCLUSIONS: This case series supports the use of tocilizumab as a therapeutic option for rapid resolution of haemolysis. It is generally widely available and should be considered a suitable and cost-effective alternative to currently available options.

Keywords:  hyperhaemolysis; sickle; tocilizumab

DOI:  https://doi.org/10.1111/tme.70026
J Blood Med. 2025 ;16 445-455

Erythrocyte Alloimmunization and Transfusion Strategies in Sickle Cell Disease: A Single-Center Analysis.

Abdulaziz Yusuf, Abrar Ahmad, Hesham A El-Beshbishy, Heba Badie Gong, Chahed Walid Chahdah, Tahani Bakhsh.

   Aim: Alloimmunization (the production of antibodies against foreign red blood cell (RBC) antigens) is a significant complication in patients with sickle cell disease (SCD) who require chronic transfusion. This retrospective study examined the distribution of ABO and Rh phenotypes in SCD patients at Dr. Soliman Fakeeh Hospital in Jeddah (DSFH-J) and their implications for alloimmunization risk. The high immunogenicity of the K antigen in the Kell system, second only to that of the D antigen in the Rh system, makes it a frequent target.
Results: Among 241 patients with SCD, the most common blood group was O (58.5%), followed by A (26.97%), B (12.03%), and AB (2.9%). The majority of patients (93.36%) were Rh-positive (D antigen-present). Among Rh antigens, the e antigen was the most prevalent (97.51%), while C antigen and c antigen were detected in 68.04% and 75.52% of patients, respectively. Within the Kell system, K was found in 8.29% of the study population. The most common antibodies detected were anti-E (20%) and anti-C (15%), indicating Rh incompatibilities to be a major concern. Kell system antibodies (anti-K) accounted for 12.5% of cases, and unidentified alloantibodies represented 17.5%. Although antibodies from other blood group systems (such as Kidd, Duffy, Lutheran, and MNS) were detected at low frequencies, their presence and known clinical significance in causing transfusion reactions underscore the need for extended RBC phenotyping to include these systems.
Conclusion: The observed distribution of Rh phenotypes and the presence of alloantibodies beyond the prevalent ones highlights the need for extended RBC phenotyping to include other blood group systems, such as Kidd and Duffy. Establishing a national blood donor registry with comprehensive RBC antigen data is a crucial step toward ensuring safer transfusions. Standardizing blood screening protocols across hospitals in Saudi Arabia and introducing routine extended RBC typing before transfusions would minimize alloimmunization risks and improve the overall patient safety.

Keywords:  RBC alloimmunization; Rh phenotype; blood transfusion; sickle cell disease

DOI:  https://doi.org/10.2147/JBM.S548152