Sickle Cell Research Articles

A machine learning-based workflow for predicting transplant outcomes in patients with sickle cell disease.

Allogeneic haematopoietic cell transplantation (HCT) with HLA-matched sibling donor remains the most established curative therapeutic option for patients with sickle cell disease (SCD). However, it is not without risks, highlighting the need for a risk stratification system. Utilizing a machine learning (ML) approach that combines clinical and imaging variables, we identified red cell distribution width and renal organ damage as important risk factors for patients undergoing HCT. This ML-based algorithm, similar to an approach previously reported for predicting mortality in patients with SCD, should be applicable to risk factor discovery in similar studies.

Evaluation of Haemoglobin F and Haemoglobin A2 among Sickle Cell Patients in Steady State at Selected Hospital in Ogun State, Nigeria

Background: Sickle cell anemia (SCA) is a genetic disorder characterized by abnormal hemoglobin variants, including hemoglobin F (Hb F) and hemoglobin A2 (Hb A2). Evaluating the levels of these hemoglobin variants in steady-state sickle cell patients can provide insights into disease prognosis and management. This study aimed to assess Hb F and Hb A2 levels among sickle cell patients in steady state at a selected hospital in Ogun State, Nigeria. Objective: To evaluate the levels of hemoglobin F (Hb F) and hemoglobin A2 (Hb A2) in sickle cell anemia patients and determine their associations with demographic factors such as age and gender. Materials and methods: A descriptive cross-sectional study was conducted at the Sickle Cell Center, Abeokuta, Ogun State, Nigeria, from September to October 2020. A total of 60 sickle cell patients in steady state were recruited using convenient sampling. Blood samples were collected, and Hb F and Hb A2 levels were measured using high-performance liquid chromatography (HPLC). Data were analyzed using SPSS version 26.0 with independent t-test and bivariate correlation. Results: The mean levels of Hb F and Hb A2 varied across age groups and genders. Hb F levels were highest in patients over 35 years (10.4 ± 12.16%) and lowest in those aged 26-30 years (3.7 ± 1.3%). The majority of participants had Hb F levels between 2-10%, with a significant association between Hb F levels and age (p = 0.038). Hb A2 levels were consistently above 3.1% in 92.6% of the study population, with no significant association with age or gender. Conclusion: There is a significant association between age and Hb F levels among steady-state sickle cell patients, while Hb A2 levels showed no significant demographic correlations. The findings suggest that Hb F may serve as a potential marker for clinical evaluation in SCA patients.

Migration Medicine: infectious and non-infectious diseases

Approximately one third of the German population has a migration background.According to the federal office for migration, in 2022 around 2,7 million people have taken refuge or have immigrated to Germany, causing major challenges for our health system. In this article, important infectious diseases, and non-infectious conditions like hemoglobinopathies are presented. To date, especially the latter are not common in Germany and must therefore move more into focus when taking care of migrants. Furthermore, new treatment options for hemoglobinopathies have been approved in the last couple of years, starting with the introduction of Luspatercept a few years ago for Beta-Thalassemias and in 2023 the introduction of Voxelotor for sickle cell disease. In 2024 the gene therapy with Exagamglogen-Autotemcel using the CRISPR/Cas molecular scissor was authorized as a new promising treatment for both conditions.

Scientometrics Analysis of Global Researches on Anemia

Background: Anemia is a condition in which the number of red blood cells or the hemoglobin concentration within them is lower than normal. This study aims to show the intellectual structure of knowledge regarding anemia and gives a comprehensive and up-to-date image of research in this area. Materials and Methods: This is a descriptive-analytical study with a scientometric approach. The PubMed database was searched for research publications indexed under "anemia" including 8484 records between 2011 and 2020. Data were analyzed using Co-word analysis, clustering methods, and strategic diagrams with the help of SPSS and Ucinet 6 software. Results: The keyword “Anemia Sickle Cell” and two pairs of frequently used keywords, namely “Anemia, Iron *Iron” were the most frequent in the research area. The results shaped the concepts of anemia in 9 clusters. The clusters "Hydroxyurea and sickle cell anemia", "Fetus transfusion", "Management of Thalassemia Major", "Hemolytic Uremic Syndrome", "Management and Control of Anemia", "Chronic Kidney Failure and Anemia", "Hematopoietic Stem Cell Transplantation" are topics that may be emerging or disappearing. The “Thalassemia and blood transfusion" are immature clusters. Conclusion: This study uses co-word networks that indicate important links between keywords of the research areas. Most research approaches are in the therapeutic aspects. Despite the importance of the effect of anemia on all levels of society, including economics, education, and other types of anemia, as well as its impact on learning and mental disorders, these subjects have not been given sufficient consideration.

Prescribing Hydroxyurea in Sickle Cell Disease Patients: The Pattern and Association with Co-Prescribed Medications Used to Manage the Disease Complications.

Background and Objectives: Hydroxyurea (HU) is an effective medication used to reduce the frequency of painful crises associated with sickle cell disease (SCD). However, data describing its prevalence among SCD patients in the Eastern Region of Saudi Arabia are scarce. This is a multi-center, retrospective, cross-sectional study that aims to investigate the pattern of prescribing HU in SCD patients and to determine the association between prescribing HU and other co-prescribed medications used to manage SCD complications. Methods: Data were collected from patients who visited the hematology clinics of Al-Qatif Central Hospital (QCH) and King Fahad Hospital in Hofuf (KFHH) between June 2021 to May 2023. The data included demographics, prescribed medications, and recent laboratory test results, all of which were collected from patients' medical records. Descriptive statistics were utilized to assess the difference between HU users vs. non-users. A binary logistic regression model was used to determine the association between prescribing HU and co-prescribed medications used to manage SCD complications. The results are presented as the odds ratio (OR) and 95% confidence interval (95% CI). Results: This study included 2816 SCD patients with a 56% prevalence of HU prescription. HU was prescribed for young age groups more often compared to old age group patients. Young males were more likely to be prescribed with HU compared to females, and it becomes dominant in females after the age of 36. HU users were more likely to have paracetamol (69% vs. 53%, OR = 1.9, 95% CI 1.6-2.2), NSAIDs (50% vs. 35%, OR = 1.7, 95% CI 1.5-2), and opioids (41% vs. 37%, OR = 1.3, 95% CI 1.1-1.6) co-prescribed, and less often to have laxatives (8% vs. 5%, OR = 0.66, 95% CI 0.48-0.9) and anticoagulants (22% vs. 15%, OR = 0.56, 95% CI 0.46-0.68) co-prescribed compared to non-users. Conclusions: The pattern of prescribing HU, supported by the association findings, raises concerns about patients' compliance and adherence to HU therapy. Early health education, specifically to young female SCD patients, is warranted to increase the success rate of HU therapy.

The potential role of increased miR-144 expression in Egyptian sickle cell disease patients

The potential role of increased miR-144 expression in Egyptian sickle cell disease patients

Maternal and infant outcomes in women with sickle cell disease: a matched cohort study

ObjectiveWomen with sickle cell disease (SCD) have adverse maternal and infant outcomes. Our aim was to determine whether the outcomes of SCD mothers and their infants differed from African or...

Management of acute pain in adults with sickle cell disease: the experience of the Clinical Hematology Department of the University of Dakar.

The evolution of sickle cell disease (SCD) is marked by the occurrence of painful episodes linked to the obstruction of microvessels by sickle cells, known as vaso-occlusive crisis (VOC). The aim of this work was to report the practical aspects of the management of acute pain in adults with SCD. Recommendations based on these practices are also provided. This prospective, cross-sectional, descriptive, and analytical study was conducted over a four-month period of all sickle cell patients admitted to emergency departments for VOC. The parameters studied were sociodemographic, clinicobiological, therapeutic, and evolutionary. There were 118 cases of VOC identified, representing a prevalence of 78.14% of sickle cell emergencies. The mean age of the patients was 28.41 years. The SS sickle cell phenotype accounted for 86.61% of the cases. Osteoarticular pain was the reason for admission for 88.39% of the patients; it was located in the lower limbs in 39.08% and in the spine in 27.1%. Pain intensity was moderate in 6.25% of the patients, intense in 31.25%, and unbearable in 55.55%. Multimodal analgesia was the most commonly used treatment method, combining those of levels one and two (74.31%) and levels one and three (8.25%). The mean dose of morphine administered was 17.14 mg when morphine alone was prescribed for titration, 13.57 mg when paracetamol and morphine were combined, and 15.83 mg when nefopam and morphine were combined. Clinical outcome was favorable in 68.87% of the cases. Wide variability was observed in the modalities of analgesic treatment of sickle cell VOC. These variations reflect different views on the appropriateness of opioids. This study highlights the efficacy of multimodal analgesia in the management of acute pain in patients with SCD, particularly in regard to morphine sparing. Context-specific recommendations will be needed to harmonize practices.

Navigating the nexus of personalized medicine and healthcare management: Advancing paediatric pain management modalities in sickle cell disease through thematic analysis for ages 1–12

ABSTRACT Sickle cell disease (SCD) affects millions of people and is a significant public health concern due to the severe pain crises it causes, often requiring emergency care and leading to hospitalization. Effective pain management strategies are crucial to improving the quality of life of children with SCD, particularly those aged 1 to 12 years, who are especially vulnerable. This study evaluates the effectiveness and suitability of various healthcare management strategies, with a specific focus on pain management modalities for this paediatric population. Through a thematic analysis of 36 articles from major healthcare databases, five key themes were identified: cognitive behavioral therapy (CBT) and complementary alternative medicine (CAM), digital and technological pain management methods, pain medications, individualized pain plans and enhancement strategies aimed at improving protocols. The findings highlight critical opportunities to advance pain management approaches and address current care gaps. The study underscores the importance of integrating parents and caregivers into the care process and addressing health inequalities that affect treatment outcomes. Evidence reveals that existing research on paediatric SCD pain management remains inadequate, and future studies are urgently needed to establish clear guidelines that improve treatment efficacy and translate into actionable evidence-based practices for this vulnerable population.

Prevalence of Sacroiliac Joint Involvement in Patients with Sickle Cell Disease

Prevalence of Sacroiliac Joint Involvement in Patients with Sickle Cell Disease

Prevent Acute Chest Syndrome checklist (PACScheck): A quality improvement initiative to reduce acute chest syndrome.

Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD). The Prevent Acute Chest Syndrome checklist (PACScheck) was created to drive appropriate ordering of opioids, incentive spirometry (IS), intravenous fluids (IVF), evaluation of oxygen desaturation, and bronchodilator use. Decrease the development of ACS by 5% in a hospitalized pediatric SCD population. A multidisciplinary team conducted a quality improvement (QI) project between April 2020 and August 2021 on an inpatient pediatric hematology unit. At-risk hospitalizations were patients with SCD who did not have ACS upon hospital admission. PACScheck was implemented and weekly run charts assessed documentation. Process control (p) charts, geometric control (g) charts, and chi-square tests assessed checklist process measures pre- and post-PACScheck. G chart assessed the number of encounters between ACS events. A total of 483 at-risk hospitalizations were identified in the 12 months prior and 363 during the study period. A g chart demonstrated that fewer encounters developed ACS during PACScheck. A p chart demonstrated that IS documentation increased during PACScheck. A run chart of PACScheck documentation demonstrated a median of 100% documentation at least once per hospitalization during the last six months of the intervention. Development of ACS can be reduced by implementing a best-practices checklist (PACScheck) on an inpatient pediatric hematology unit with a multidisciplinary team.

Hydroxyurea Pharmacokinetic Evaluation in Patients with Sickle Cell Disease

Background: Hydroxyurea (HU), also known as hydroxycarbamide, is an oral ribonucleotide reductase inhibitor. In 1999, the United States Food and Drug Administration (FDA) approved HU for the treatment of sickle cell disease (SCD). Since then, it has become the cornerstone in the management of SCD patients, helping to reduce vaso-occlusive crises, acute chest syndrome, the need for blood transfusions, hospitalizations and mortality. There is considerable variability among individuals in HU pharmacokinetic (Pk) parameters that can influence treatment efficacy and toxicity. The objective of this work is part of a clinical study aimed at investigating HU Pk and determining the optimal sampling time to estimate the Area Under the Curve (AUC) in SCD patients. Methods: HU plasma concentration in 80 patients at various time points (2, 4, 6, 24 h) following a 48-h drug washout was quantified using High-Pressure Liquid Chromatography (HPLC) coupled with an ultraviolet (UV) detection method previously described in the literature and adapted to new conditions with partial modifications. Results: The mean HU administered dose was 19.5 ± 5.1 mg/kg (range: 7.7–37.5 mg/kg). The median AUC quantified in plasma patients was 101.3 mg/L/h (Interquartile Range (IQR): 72.5–355.9) and it was not influenced by the weight-based dose. However, there was a strong positive correlation between AUC and Body Mass Index (BMI) as well as dose per Body Surface Area (BSA). Along with a three-point approach for AUC determination present in the literature, we show results obtained from a four-point sampling strategy, which is more useful and effective for better optimizing dose escalation to the maximum tolerated dose (MTD). Moreover, we observed that most patients achieved the maximum HU plasma concentration two hours after drug administration, regardless of age differences. Conclusions: HU treatment, which represents a milestone in the treatment of SCD due to its ability to reduce disease complications and improve patients’ quality of life, requires careful monitoring to optimize the individual dose for saving potential side effects and/or adverse events.

ASH and Federal Officials Hold Town Hall on Sickle Cell Disease

ASH and Federal Officials Hold Town Hall on Sickle Cell Disease

Zinc finger nuclease-mediated gene editing in hematopoietic stem cells results in reactivation of fetal hemoglobin in sickle cell disease

BIVV003 is a gene-edited autologous cell therapy in clinical development for the potential treatment of sickle cell disease (SCD). Hematopoietic stem cells (HSC) are genetically modified with mRNA encoding zinc finger nucleases (ZFN) that target and disrupt a specific regulatory GATAA motif in the BCL11A erythroid enhancer to reactivate fetal hemoglobin (HbF). We characterized ZFN-edited HSC from healthy donors and donors with SCD. Results of preclinical studies show that ZFN-mediated editing is highly efficient, with enriched biallelic editing and high frequency of on-target indels, producing HSC capable of long-term multilineage engraftment in vivo, and express HbF in erythroid progeny. Interim results from the Phase 1/2 PRECIZN-1 study demonstrated that BIVV003 was well-tolerated in seven participants with SCD, of whom five of the six with more than 3 months of follow-up displayed increased total hemoglobin and HbF, and no severe vaso-occlusive crises. Our data suggest BIVV003 represents a compelling and novel cell therapy for the potential treatment of SCD.

Novel gene therapies for sickle cell disease, Duchenne muscular dystrophy, and hemophilia A.

This article discusses novel genetic therapies for sickle cell disease, Duchenne muscular dystrophy, and hemophilia A. Gene therapies have the potential to deliver more targeted and effective approaches to treatment, especially for rare diseases for which the availability of approved therapies is limited. This article describes the first FDA-approved CRISPR/Cas9 treatment and the treatment protocols, indications, warnings, precautions, cost, and contraindications of four novel genetic therapies.

Assessment of serum protein profile in sickle cell disease

Background: Sickle Cell disease (SCD) is known to be caused by a mutation in the beta-globin gene of the hemoglobin that affects the red blood cells (RBCs) and is passed down through generations. This study was carried out to determine the effect of sickling of RBC on serum protein profile in SCD individuals. Methods: A case-controlled study was carried out among 80 patients. They were forty-five sickle cell disease individuals (HbSS) attending Children Specialist Hospital Ilorin and thirty-five healthy controls (HbAA). The levels of total protein and albumin were determined spectrophotometrically and serum protein electrophoresis (SPE) was carried out using cellulose acetate electrophoresis. Results: Significant hypoalbuminemia and hypergammaglobulinemia were observed in SCD groups compared with controls. A higher proportion of the SCD group, 11(25%) had hypergammaglobulinemia and 21(49%) had hypoalbuminemia (P<0.05). Plasma protein electrophoresis in SCD patients shows an intense colour at the gamma region which was not seen in control. There was a significant relationship between the patterns of serum protein electrophoresis and the frequency of crisis. Conclusions: Sickle cell disease crisis and other associated underlying conditions may be prevented early through assessment of serum protein profile, especially SPE. Hypergammaglobulinemia and hypoalbuminemia may be associated with frequent episode of crisis.

Liver and renal biochemical profiles of people with sickle cell disease in Africa: a systematic review and meta-analysis of case-control studies

BackgroundSickle cell disease (SCD) is a genetic blood disorder characterized by a painful vaso-occlusive crisis due to the sickling of red blood cells in capillaries. Complications often lead to liver and renal dysfunctions, contributing to morbidity and mortality, particularly for children under 5. This systematic review and meta-analysis aimed to evaluate the liver and renal functions of people with SCD (HbSS) compared to those without it (HbAA) in Africa.MethodsThe protocol was registered with PROSPERO (CRD42022346771). We searched PubMed, Embase, Web of Science, and Google Scholar using the keywords “liver function”, “renal function”, “sickle cell disease”, and “Africa” on 6th May 2023 for peer-reviewed articles with abstracts in English. We included case-control studies comparing SCD (HbSS) with controls without hemoglobinopathies (HbAA). We used the random-effect model to calculate the pooled average values for the blood tests of people with SCD in RStudio version 4.2.2.ResultsOverall, 17 articles were analyzed from five African countries involving 1312 people with SCD and 1558 controls. The pooled mean difference of liver enzymes aspartate transaminase (AST) was 8.62 (95% CI − 2.99–20.23, I2 = 97.0%, p < 0.01), alanine transaminase (ALT) 7.82 (95% CI − 0.16–15.80, I2 = 99%, p < 0.01) and alkaline phosphatase (ALP) − 2.54 (95% CI − 64.72 – 59.64, I2 = 99%, p < 0.01) compared to controls. The pooled mean difference for the renal biochemical profiles creatinine − 3.15 (95% CI − 15.02; 8.72, I2=99%, p < 0.01) with a funnel plot asymmetry of t = 1.09, df = 9, p = 0.3048 and sample estimates bias of 6.0409. The pooled mean difference for serum urea was − 0.57 (95% CI − 3.49; 2.36, I2 = 99%, p < 0.01), and the estimated glomerular filtration (eGFR) rate was 19.79 (95% CI 10.89–28.68 mL/min/1.73 m2, I2 = 87%, p < 0.01) compared to controls.ConclusionPeople with SCD have slightly elevated liver enzymes and estimated glomerular filtration rates compared to controls in Africa. With all the heterogeneity (I2) > 50%, there was substantial variation in the reported articles’ results.Systematic review registrationPROSPERO CRD42022346771

Exploring TFE3-Rearranged Renal Cell Carcinoma: A Case Study showing minimal expression of PAX-8

Abstract Introduction/Objective TFE3-rearranged renal cell carcinoma accounts for 1.6-4% of adult renal cell carcinomas (RCC). The histological characteristics of this entity can mimic many other renal cell neoplasms and definite diagnosis is based on immunohistochemical (IHC) and fluorescent in situ hybridization (FISH) analysis. Nonspecific IHC findings can lead to diagnostic challenges delaying confirmatory studies and underdiagnosis. Methods/Case Report A 28-year-old male with sickle cell disease and a right kidney multilocular cystic mass incidentally found during evaluation of splenomegaly underwent partial nephrectomy. The tumor showed papillary, alveolar and sheet-like growth patterns composed of eosinophilic to clear cells with pleomorphic nuclei, including multinucleate forms. Initial ancillary studies showed minimal neoplastic expression (less than 5%) of PAX-8. Repeat PAX-8 yielded similar results and laboratory controls were evaluated successfully. A full work-up showed positivity of AMACR (diffuse), CD10 (diffuse), Cathepsin K (patchy), CK7 (focal), CAIX (focal), and no significant expression of pancytokeratin, HMB-45, Melan-A and SMA. Fumarate hydratase was retained, and the tumor showed a non-specific staining pattern of S (2-succinyl)-cysteine. Controls were appropriate. A high suspicion for a TFE-rearranged RCC was maintained, and a final diagnosis was confirmed with FISH analysis demonstrating a TFE3 (Xp11.23) rearrangement. Results (if a Case Study enter NA) NA Conclusion Reports in the literature detail diffuse PAX-8 expression in TFE3-rearranged RCC. A high index of suspicion based on morphology in our case prompted FISH analysis leading to correct diagnosis. This case highlights the inconsistencies in the reported IHC profile of this entity. More studies are required to elaborate the presentations of this RCC subtype with numerous histologic mimics including the spectrum of immunostaining patterns to better assist patient care for this uncommon variant.

Assessing the Effect of Changing the Average Hematocrit in Red Blood Cell (RBC) Units on the Post- Procedure Hematocrits of Patients Undergoing Erythrocytapheresis

Abstract Introduction/Objective Red cell exchange (RCE) is utilized as a therapeutic or prophylactic procedure for patients with sickle cell disease (SCD). When performing RCE, three hematocrits (Hct) are taken into account: pre-procedure and goal Hct for the patient and average Hct (avg-Hct) of the transfused RBC units. Although there is no definitive community consensus, many transfusion services employ RBC unit avg-Hct of 55% per available guidance. Our center anecdotally observed that utilizing RBC unit avg-Hct of 55% often resulted in post-procedure patient Hcts higher than intended goal Hct, potentially causing hyperviscosity. This study aims to examine the effect of changing the avg-Hct from 55% to 60% on the accuracy of post-procedure HCTs, with the 60% avg-Hct employed based on prior quality studies of RBC units at our facility. Methods/Case Report We performed a retrospective chart review for SCD patients receiving chronic, prophylactic RCE at a large academic hospital, collecting the following for each procedure: goal procedure Hct, number of RBC units exchanged, avg-Hct used, and pre-/post-procedure patient Hcts. Differences between goal Hcts and post- procedure Hcts for each procedure in the avg-Hct=55% and avg-Hct=60% groups were calculated. Next, mean calculated differences for both groups were compared using a two-sample t-test (P&amp;lt;0.05 was considered significant). Results (if a Case Study enter NA) From 1/2023–2/2024, 293 prophylactic RCEs were performed for SCD patients. Median number of RBC units per procedure was 7, with 51% of procedures (n=149) employing unit avg-Hct=55%, while 49% of procedures (n=144) used a unit avg-Hct=60%. Post-procedure patient Hct and goal Hct differences were statistically different according to unit avg-Hct values utilized (mean difference=1.31% for avg-Hct=55% vs mean difference=0.52% for avg-Hct=60%; P&amp;lt;0.0001). Conclusion Changing our protocol to use RBC unit avg-Hct=60% resulted in post-procedure patient Hcts significantly closer to intended goals. Utilization of a more accurate average-Hct value has a substantial impact on post-procedure Hct in RCEs and may limit adverse events.

Short-term Outpatient Parenteral Antimicrobial Therapy Administration in the Pediatric Emergency Department: Feasibility, Safety, and Outcome.

The practice of administration of intravenous (IV) antimicrobial therapy in outpatient settings (OPAT) is a low-cost alternative to in-patient admission and treatment. There is, however, limited evidence supporting OPAT management protocols for children. The primary objective of this study was to describe the use of pediatric emergency-based OPAT, as well as the safety of this practice. The study was a prospective, observational study conducted in pediatric emergency department of a tertiary care hospital. Children younger than 14 years who required pediatric emergency department-based OPAT were included in the study. Three hundred and ninety-two children were included in the study. The mean duration of OPAT was 3.5 days. Ceftriaxone was the most frequently used antimicrobial. Chest infection was the commonest indication, followed by sickle cell disease with fever and soft tissue infections. There were no major intravenous line-related complications over course of treatment. Most of the patients (89.5%) completed the OPAT course successfully. Only 10.4% patients required subsequent hospital admission, with failure to improve on the OPAT protocol being the main reason patients for admission. None of the admitted patients required intensive care settings or faced unexpected morbidity. Our results affirm that pediatric emergency-based OPAT is a safe yet effective practice in children with good clinical outcome. We believe that a reduction in admissions translates to better hospital resource utilization.