Prevalence of hemoglobinopathies among Malayali tribes of Jawadhu hills, Tiruvannamalai district, Tamil Nadu, India: a community-based cross-sectional study.

BACKGROUND: Hemoglobin (Hb), a red pigment of red blood cells (RBCs), carries oxygen from the lungs to different organs of the body and transports carbon dioxide back to the lungs. Any fault present in the Hb structure leads to undesirable functional effects of the RBCs, such as sickle cell anemia (SCA), thalassemia, etc. Hemoglobinopathies affect around 7% of people in both developed and developing countries globally. The aim of the present study was to determine the prevalence and carrier frequencies of hemoglobinopathies including SCA, thalassemia, and other abnormal Hb variants among Malayali tribes in the Jawadhu hills of Tiruvannamalai district, Tamil Nadu, India. METHODS: A community-based cross-sectional study was carried out among 443 Malayali tribes inhabiting the Jawadhu hills of Tiruvannamalai district from July 2022 to September 2022. The RBC indices were analyzed using an automated 5-part hematology analyzer (Mindray, BC-5150) and hemoglobin fractions were done using the HPLC system (Bio-Rad, D-10) following standard protocols. FINDINGS: A total of 443 participants were screened, out of whom 14.67% had an abnormal Hb fraction, 83.30% were identified as normal, and 2.03% were borderline. Notably, the study revealed a prevalence of 0.68% for the α-thalassemia trait and 13.99% for the ß-thalassemia trait. INTERPRETATION: Haemoglobinopathies, specifically the ß-thalassemia trait, were most prevalent among the Malayali tribal population of Tamil Nadu residing in the Jawadhu hills of Tiruvannamalai district. Hence, we need special attention for creating awareness, increasing hemoglobinopathies screening programs, and improving the importance of tribal health conditions by the government and non-governmental organizations (NGOs) for the betterment of the ethnic tribes.

Cardiovascular Consequences of Sickle Cell Disease.

Background: Sickle cell disease is an inherited blood disorder which can lead to severe complications, particularly in the cardiovascular and respiratory systems, potentially resulting in arrhythmias, pulmonary hypertension (PH), and cardiomegaly. This study aims to investigate the risk of PH and arrhythmias in adult SCD patients. Methods: Retrospective analysis of medical records from King Abdulaziz University Hospital (KAUH) for patients with SCD aged 15 and above between 2009 and 2021. The study included 517 patients, with echocardiograms and electrocardiograms assessed according to the European Society of Cardiology/the European Respiratory Society (ESC/ERS) guidelines for categorizing PH risk (low, moderate, high) and detecting arrhythmias. Data analysis employed the Statistical Package for the Social Sciences (SPSS), utilizing quantitative and qualitative data representation. Multivariate logistic regression identified independent risk factors with odds ratios at a 95% confidence interval (CI). Results: Among participants, 50.3% were male, with a total sample average age of 34.45 ± 9.28 years. Results indicated that 1.4% of patients experienced arrhythmias, 3.7% had a moderate PH risk, and 3.3% were classified as high PH risk. Logistic regression revealed significant independent risk factors for PH and arrhythmia in patients with SCD, with chronic kidney disease (CKD) carrying the highest odds (26.4 times higher odds of PH and 15.36 times higher odds of arrhythmias). Conclusion: Patients with SCD are at risk for developing PH and various arrhythmias but are often underdiagnosed. Key risk factors for PH included CKD, liver cirrhosis, and pre-existing cardiac conditions. Arrhythmias were significantly associated with CKD and pre-existing cardiac conditions. To mitigate these risks, we recommend involving a multidisciplinary healthcare team in the care of adult patients with SCD. Future prospective studies are advised for early detection of PH and arrhythmias in hemoglobinopathy patients, potentially reducing mortality.

Haemoglobinopathies and other rare anemias in Spain: ten years of a nationwide registry (REHem-AR).

REHem-AR was created in 2013. The progressive implementation of neonatal screening for haemoglobinopathies in Spanish autonomous communities where the registry had not been implemented, as well as the addition of new centres during this period, has considerably increased the sample of patients covered. In this study, we update our previous publication in this area, after a follow-up of more than 5 years. An observational, descriptive, multicentre and ambispective study of adult and paediatric patients with haemoglobinopathies and rare anaemias registered in REHem was performed. The data are from a cross-sectional analysis performed on 1 June, 2023. The study population comprised 1,756 patients, of whom 1,317 had SCD, 214 had thalassaemia and 224 were diagnosed with another condition. Slightly more than one third of SCD patients (37%) were diagnosed based on neonatal bloodspot screening, and the mean age at diagnosis was 2.5 years; 71% of thalassaemia patients were diagnosed based on the presence of anaemia. Vaso-occlusive crisis and acute chest syndrome continue to be the most frequent complications in SCD. HSCT was performed in 83 patients with SCD and in 50 patients with thalassaemia. Since the previous publication, REHem-AR has grown in size by more than 500 cases. SCD and TM are less frequent in Spain than in other European countries, although the data show that rare anaemias are frequent within rare diseases. REHem-AR constitutes an important structure for following the natural history of rare anaemias and enables us to calculate investment needs for current and future treatments.

Context base editing for splice correction of IVSI-110 ß-thalassemia.

ß-Thalassemia is brought about by defective ß-globin (HBB [hemoglobin subunit ß]) formation and, in severe cases, requires regular blood transfusion and iron chelation for survival. Genome editing of hematopoietic stem cells allows correction of underlying mutations as curative therapy. As potentially safer alternatives to double-strand-break-based editors, base editors (BEs) catalyze base transitions for precision editing of DNA target sites, prompting us to reclone and evaluate two recently published adenine BEs (ABEs; SpRY and SpG) with relaxed protospacer adjacent motif requirements for their ability to correct the common HBBIVSI-110(G>A) splice mutation. Nucleofection of ABE components as RNA into patient-derived CD34+ cells achieved up to 90% editing of upstream sequence elements critical for aberrant splicing, allowing full characterization of the on-target base-editing profile of each ABE and the detection of differences in on-target insertions and deletions. In addition, this study identifies opposing effects on splice correction for two neighboring context bases, establishes the frequency distribution of multiple BE editing events in the editing window, and shows high-efficiency functional correction of HBBIVSI-110(G>A) for our ABEs, including at the levels of RNA, protein, and erythroid differentiation.

Prevalence of fetomaternal Rhesus incompatibility at the tertiary care hospital: a cross-sectional study.

Background: Fetomaternal Rhesus incompatibility is a medical condition that affects the pregnant woman [of blood group (A, B, AB, O) and a negative Rhesus] and the foetus (of positive Rhesus). The objective of this study is to determine the prevalence and to present the clinical characteristics of fetomaternal Rhesus incompatibility in a tertiary care hospital. Methods: The authors conducted a retrospective cross-sectional study and 37 participants were recorded during the study period of 4 years. Results: A total of 11 898 pregnant women admitted to the maternity and 37 of them (women with blood groups A, B, AB or O and with a negative Rhesus) participated in our study, including a frequency of 0.31%. Thirty cases of fetomaternal Rhesus incompatibility were recorded in new-borns. 27 (73%) of the women are from the urban region and the age group between 21 and 25 is the most affected with 37.8%. Twenty-two (59.5%) of pregnant women have blood group O (and negative Rhesus) and primiparous women are the most affected with 64.9%. For the discovery of allo-immunization, 43.2% of women discovered it during the second pregnancy and 48.7% women received a single infusion of Anti-D serum during the first pregnancy. Twelve (40%) new-borns developed jaundice as a perinatal prognosis. Conclusion: Fetomaternal Rhesus incompatibility remains a major problem of maternal health because it is likely to lead to the formation of antibodies in women, which by crossing the placental barrier, they destroy red blood cells and thus cause serious complications.

Premarital Screening is Pivotal in Reducing the Births of Babies Affected with Thalassemia Major in Iraq.

Thalassemia major is one of the health problems in Iraq, especially in Kurdistan. Pre-marriage mandatory preventive screening program was established in Kurdistan in 2008, which allowed us to study the prevalence of different hemoglobinopathies among newly married young adults in this region. A total of 1154 subjects (577 couples) attending the Koya district, premarital Health center, were screened using red cell indices. Those who had mean corpuscular volume (MCV)<80 fl and mean corpuscular hemoglobin (MCH)<27 pg had high-performance liquid chromatography and iron studies. Out of 1154 individuals that were evaluated, 183 (11.9%) had low MCV and MCH. Of the former 183 subjects, 69 (5.97%) had ß-thalassemia trait, 10 (0.86%) had δß-thalassemia trait, and no other hemoglobinopathies were recorded in our study. There was second-degree consanguinity in 4.7% of all 577 couples. In two couples, both partners had ß-thalassemia trait and both were consanguineous. Both couples decided to separate after counseling. Based on the current study, the role of the premarital screening program in decreasing the number of new thalassemia major cases among the Kurdish population is laudable. Therefore, mandatory premarital screening is advised in all parts of Iraq.

Good engraftment after reduced intensity targeted busulfan-based conditioning and matched related donor hematopoietic cell transplantation in hemoglobinopathies.

BACKGROUND: Hematopoietic cell transplantation (HCT) is an established curative therapy for transfusion-dependent thalassemia (TDT) and sickle cell disease (SCD). The latest American Society of Hematology guidelines recommend myeloablative preparative regimen in patients under 18 years of age. PROCEDURE: The objective was to demonstrate safety and efficacy of a reduced intensity conditioning (RIC) regimen including high-dose fludarabine, anti-thymocyte globulin, and targeted busulfan as a single alkylator to sub-myeloablative exposures. RESULTS: Between 2012 and 2021, 11 patients with SCD and five patients with TDT and matched related donor (MRD) HCT were included. The median age at transplantation was 8.3 years (range: 3.7-18.8 years). The median administered busulfan AUC was 67.4 mg/L×h (range: 60.7-80 mg/L×h). Overall survival was 93.8% and event-free survival 87.5% with one engrafted SCD patient with pre-existing moyamoya disease succumbing after drainage of a subdural hematoma. One SCD patient developed a secondary graft failure and was treated with a second HCT. Myeloid chimerism was full in all other patients with a median follow-up time of 4.1 years (range: 2.0-11.1 years), whereas T-cell donor chimerism was frequently mixed. CONCLUSION: This RIC conditioning followed by MRD HCT is sufficiently myeloablative to cure pediatric patients with hemoglobinopathies without the need for additional total body irradiation or thiotepa.

Angioid Streaks Remain a Challenge in Diagnosis, Management, and Treatment.

Aim: Angioid streaks (ASs) are a rare retinal condition and compromise visual acuity when complicated with choroidal neovascularization (CNV). They represent crack-like dehiscences at the level of the Bruch's membrane. This objective narrative review aims to provide an overview of pathophysiology, current treatment modalities, and future perspectives on this condition. Materials and Methods: A literature search was performed using "PubMed", "Web of Science", "Scopus", "ScienceDirect", "Google Scholar", "medRxiv", and "bioRxiv." Results: ASs may be idiopathic, but they are also associated with systemic conditions, such as pseudoxanthoma elasticum, hereditary hemoglobinopathies, or Paget's disease. Currently, the main treatment is the use of anti-vascular endothelial growth factors (anti-VEGF) to treat secondary CNV, which is the major complication observed in this condition. If CNV is detected and treated promptly, patients with ASs have a good chance of maintaining functional vision. Other treatment modalities have been tried but have shown limited benefit and, therefore, have not managed to be more widely accepted. Conclusion: In summary, although there is no definitive cure yet, the use of anti-VEGF treatment for secondary CNV has provided the opportunity to maintain functional vision in individuals with AS, provided that CNV is detected and treated early.

Spanish registry of hemoglobinopathies and rare anemias (REHem-AR): demographics, complications, and management of patients with ß-thalassemia.

INTRODUCTION: The increase in the number of patients with hemoglobinopathies in Europe in recent decades highlights the need for more detailed epidemiological information in Spain. To fulfil this need, the Spanish Society of Pediatric Hematology and Oncology (SEHOP) sponsored the creation of a national registry of hemoglobinopathies known as REHem-AR (Spanish Registry of Hemoglobinopathies and Rare Anemias). Data from the transfusion-dependent (TDT) and non-transfusion-dependent (NTDT) ß-thalassemia cohorts are described and analyzed. METHODS: We performed an observational, multicenter, and ambispective study, which included patients of any age with TDT and NTDT, registered up to December 31, 2021. RESULTS: Among the 1741 patients included, 168 cases of thalassemia were identified (103 TDT and 65 NTDT-patients). Survival at 18 years was 93% for TDT and 100% for NTDT. Regarding management, 80 patients with TDT (77.7%) and 23 patients with NTDT (35.4%) started chelation treatment during follow-up, with deferasirox being the most widely used. A total of 76 patients within the TDT cohort presented at least 1 complication (73.8%), the most frequent being hemosiderosis and osteopenia-osteoporosis. Comparison of both cohorts revealed significant differences in the diagnosis of hepatic hemosiderosis (p = 0.00024), although these were not observed in the case of cardiac iron overload (p = 0.27). DISCUSSION: Our registry enabled us to describe the management of ß thalassemia in Spain and to analyze the morbidity and mortality of the cohorts of patients with TDT and NTDT. Complications related to iron overload in TDT and NTDT account for most of the morbidity and mortality of the disease, which is associated with a considerable social, psychological, and economic impact, although cardiac, osteopathy and endocrinological complications requiring more attention. The convenience and simplicity of online registries make it possible to homogenize variables and periodically update data, thus providing valuable information on these diseases.

Bone Health Impairment in Patients with Hemoglobinopathies: From Biological Bases to New Possible Therapeutic Strategies.

Hemoglobinopathies are monogenic disorders affecting hemoglobin synthesis. Thalassemia and sickle cell disease (SCD) are considered the two major hemoglobinopathies. Thalassemia is a genetic disorder and one of the major hemoglobinopathies determined by an impairment of globin chain production, which causes an alteration of erythropoiesis, an improvement in hemolysis, and an alteration of iron homoeostasis. In SCD, the mutations are on the ß-globin chain of hemoglobin which results in a substitution of glutamic acid by valine with consequent formation of Hemoglobin S (HbS). Several factors are involved in bone metabolism alteration in patients with hemoglobinopathies, among them hormonal deficiency, bone marrow hyperplasia, iron overload, inflammation, and increased bone turnover. Bone metabolism is the result of balance maintenance between bone deposition and bone resorption, by osteoblasts (OBs) and osteoclasts (OCs). An impairment of this balance is responsible for the onset of bone diseases, such as osteoporosis (OP). Therefore, here we will discuss the alteration of bone metabolism in patients with hemoglobinopathies and the possible therapeutic strategies to contain and/or counteract bone health impairment in these patients, taking into consideration not only the pharmacological treatments already used in the clinical armamentarium, but also the new possible therapeutic strategies.

Early Onset of Severe Anemia Caused by Hb Calgary (HBB: C.194G > T): Another Case Report.

Unstable hemoglobin (Hb) variants are a rare cause of congenital hemolytic anemia. We describe a Chinese girl who presented with transfusion-dependent anemia in early infancy. Her diagnosis of Hb Calgary [ß64(E8)Gly > Val; HBB:c.194G > T] was not made until molecular testing was performed at the age of 5 years. Our case highlights the importance of early genetic testing in order to make the diagnosis, which may not only be useful for patient management and family counseling, but also for avoiding further unnecessary investigative attempts.

Red blood cell indices in different hemoglobinopathies: A cross-sectional study in Eastern India.

Introduction: Beta thalassemia and hemoglobin (HbE)-related hemoglobinopathies are common public health problems in developing countries. High-performance liquid chromatography (HPLC) is currently the diagnostic test of choice for carrier detection, but it is costly. Hence, some initial screening and complementary tests are required, which can be affordable. Aims: To find out the distribution of different red blood cell (RBC) indices in beta thalassemia trait (BTT) and HbE-related hemoglobinopathies and to determine their significance as screening tests to distinguish between these hemoglobinopathies. Study Settings and Design: This observational cross-sectional study has been carried out at an NABL (National Accreditation Board for Testing and Calibration Laboratories)-accredited Laboratory of Eastern India with approval from the concerned Institutional Ethics Committee from January 2021 to March 2021. Methods and Material: : HPLC tests and complete hemograms were performed on 2247 ethylenediaminetetraacetic acid anti-coagulated blood samples over 3 months. Patients <1 year of age or having a history of blood transfusion within the past 06 months were excluded. Statistical Analysis: : One-way analysis of variance along with Bonferroni post-hoc test was performed to find out significant differences of means of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), hemoglobin%, red blood cell (RBC) count, and red cell distribution width (RDW-CV) among concerned hemoglobinopathies. Results: The results show a significant difference of total RBC count, RDW, MCV, MCH, and MCHC between BTT and E-trait. No significant difference of mean was found between HbE homozygous and E-beta. E-trait differs from both HbE homozygous and E-beta significantly in three parameters, namely, RDW, MCV and MCH. A value of MCV at ≤73.8 fl and MCH at ≤21.9 pg may be a clue of diagnosis for BTT rather than E-trait with >90% sensitivity and >80% specificity. Conclusion: RBC indices vary significantly between BTT and other HbE-related hemoglobinopathies. They can specially be utilized to differentiate BTT and E-trait as supportive tests in addition to the gold standard test of HPLC.

Regional Prevalence of Hemoglobin C Across Saudi Arabia: An Epidemiological Survey.

INTRODUCTION: HbC is a common structural hemoglobinopathy especially in West Africa. Prevalence and regional distribution of HbC in Saudi Arabia are widely undocumented. Patients with homozygous HbC disease may have mild hemolytic anemia whereas combination with hemoglobin S (HbS) leads to a clinically severe phenotype. AIM: The current epidemiological study, considered the largest from Saudi Arabia, aimed to evaluate the regional prevalence of the HbC variant among the couples participating in the premarital screening program from 2011 to 2018. METHODS: Data from the PMSGC program were obtained for premarital screening and genetic counseling. The collected data were then entered into the SEHA platform, a centralized electronic repository for the 13 designated regions in Saudi Arabia. Hemoglobin electrophoresis samples are analyzed using either HPLC, capillary electrophoresis, or a combination of both methods to confirm the presence of abnormal hemoglobin bands. RESULTS: This study included 1,871,184 individuals from 2011 to 2018. Of those, 49.8% were males and 50.2% were females. 112,618 (6.0%) had an abnormal test. Total number of Hb C cases were 778 (0.04%). HbC trait (HbAC) was detected in 764 participants while homozygous HbC (HbCC) and combined heterozygous (HbSC) were found in 9 and 5 cases, respectively. The regions near the Red Sea have higher rates than the central and eastern regions. CONCLUSION: HbC is a rare variant in Saudi Arabia with varying regional frequencies. HbC variant is more common in Mecca and Madina regions. The geographic area of HbC distribution differs from the areas with high prevalence of HbS, which explains why HbSC disease cases are overwhelmingly rare.

Electrospray triple quadrupole mass spectrometry guides pathologists to suggest appropriate molecular testing in the identification of rare hemoglobin variants.

Background: The presumptive diagnosis of hemoglobinopathies relies on routine tests such as Complete Blood Count (CBC), peripheral blood smear, Liquid Chromatography (LC), and Capillary Electrophoresis (CE), along with clinical findings. Pathologists suggest molecular sequencing of HBA and HBB genes to correlate blood picture with clinical findings in order to identify unknown rare haemoglobin (Hb) variants or variants that coelute with Hb. This paper presents a low-resolution mass spectrometry (MS)-based method for presumptive identification of variants that eluted in zone 12 of CE, followed by molecular sequencing of the HBB gene for a definitive diagnosis of hemoglobinopathies. Methods: Eight patient samples with a variant peak in zone 12 of CE (Sebia) were analyzed using MS. The mass-to-charge ratio (m/z) observed was deconvoluted to determine the mass of Hb variants. The ß variants were subsequently confirmed through molecular sequencing. Results: Based on the intact mass of the variants, there were two samples of the α variant (α + 58 Da and α + 44 Da), and six samples of the ß variant. Out of these six ß variant samples, three were the ß + 58 Da variant, and three were the ß + 30 Da variant. By correlating the intact mass information with the CE pattern and considering the ethnicity of the patients, it was presumed that the α variants were HbJ Meerut (α + 58 Da, x-axis 102) and HbJ Paris-I (α + 44 Da, x-axis 80). Molecular analysis confirmed the identity of ß variants as Hb Rambam/HbJ Cambridge, HbJ Bangkok (+58 Da), and Hb Hofu (+30 Da). Conclusion: The mass information of Hb variants obtained using Electrospray triple quadrupole MS assists pathologists in recommending the appropriate molecular sequencing for identifying unknown variants.

Uncovering an undisclosed diagnosis: a glucose-6-phosphate dehydrogenase deficiency diagnosis in a critically ill adult.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency affects over 400 million people worldwide. The most common variant of G6PD deficiency in the United States is the A-variant, which is present amongst African-Americans. Most people with this variant, however, do not experience severe hemolysis unless under extreme circumstances. Here, we present the case of a 44-year-old African-American male who under circumstances of multiple admissions for critical illness eventually presented with a masked diagnosis of G6PD deficiency.

DHA and EPA in Sickle Cell Disease Favor Clinical Improvement and Contribute to Better Quality of Life: A Qualitative Systematic Review.

BACKGROUND: Sickle cell disease is a severe genetic disorder, and searching for therapeutic strategies is indispensable for prolonged and improved life for people affected by this condition. OBJECTIVE: This qualitative systematic review aimed to highlight the therapeutic potential of omega- 3 (n-3) in people with sickle cell disease. METHODS: The search was performed by combining sickle cell disease and n-3 descriptors in DeCS/ MeSH databases, including Scopus, PubMed, ScienceDirect, Web of Science, and Virtual Health Library. The risk of bias assessment in the primary studies was performed using the Cochrane risk of bias tool for randomized controlled trials. The evidence quality was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. RESULTS: From the 187 records identified, seven were selected for data collection. Based on the evidence, n-3 supplementation contributes to lower activation of pro-inflammatory biomarkers, improves the concentration of docosahexaenoic and eicosapentaenoic acids in the erythrocyte membrane, provides better hemostatic response, and helps in vaso-occlusive crisis, pain episodes, and hospitalization reduction. CONCLUSION: The findings suggest that n-3 adjuvant therapy favors the clinical and general aspects of people with sickle cell disease.

Identification of a rare [G γ(A γδß)0 ] -thalassemia using tandem mass spectrometry.

Thalassemias are a group of inherited monogenic disorders characterized by defects in the synthesis of one or more of the globin chain subunits of the hemoglobin tetramer. Delta-beta (δß-) thalassemia has large deletions in the ß globin gene cluster involving δ- and ß-globin genes, leading to absent or reduced synthesis of both δ- and ß-globin chains. Here, we used direct globin-chain analysis using tandem mass spectrometry for the diagnosis of δß-thalassemia. Two cases from unrelated families were recruited for the study based on clinical and hematological evaluation. Peptides obtained after trypsin digestion of proteins extracted from red blood cell pellets from two affected individuals and their parents were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Mass spectrometric analysis revealed a severe reduction in δ, ß, and Aγ globin proteins with increased G γ globin protein in the affected individuals. The diagnosis of G γ(A γδß)0 -thalassemia in the homozygous state in the affected individuals and in the heterozygous state in the parents was made from our results. The diagnosis was confirmed at the genetic level using multiplex ligation-dependent probe amplification (MLPA). Our findings demonstrate the utility of direct globin protein quantitation using LC-MS/MS to quantify individual globin proteins reflecting changes in globin production. This approach can be utilized for accurate and timely diagnosis of hemoglobinopathies, including rare variants, where existing diagnostic methods provide inconclusive results.

A comparison of the mixed and sequential use of acetaminophen and dexketoprofen in painful vaso-occlusive crises.

PURPOSE: Opioids are widely used to treat painful vaso-occlusive crises (VOC) in sickle cell disease (SCD). However, due to opioids' significant adverse effect profiles, the search for alternative therapies continues from the past to the present. The study aimed to investigate the efficacy of acetaminophen and dexketoprofen in the treatment of painful VOC. METHODS: This study is a single-center, prospective, non-randomized, single-blinded, controlled study. The study comprised two groups: the first administered acetaminophen and dexketoprofen mixed group, while the second received them sequential group. Opioids were used in patients with persistent pain despite these analgesics. Demographic and laboratory information, pain scores, opioid requirement, dose amount, side effects, and length of hospital stay of the patients were recorded. RESULTS: The study comprised 56 (100%) patients with painful VOC, 29 (51.8%) from the mixed group, and 27 (48.2%) from the sequential group. Opioid use was seen in 16 (55.2%) patients in the mixed group and 21 (77.8%) patients in the sequential group (p = 0.074). The median amount of opioid used was significantly lower in the mixed group than in the sequential group (p < 0.001). Also, the median length of hospital stay was significantly lower in the mixed group than in the sequential group (p < 0.001). CONCLUSION: Our study suggests that administering acetaminophen and dexketoprofen in the mix for the treatment of painful VOC in patients with SCD may be a more efficient approach compared to sequential administration. This approach appears to reduce opioid usage and shorten hospital stays.