Vaso-occlusive Crisis Research Articles

Schistosome Infection in the Humanized Mouse Model of Sickle Cell Disease

Introduction Sickle cell disease (SCD) is a hemoglobinopathy due to a single amino acid substitution in the β-chain of hemoglobin (Hb), in which glutamic acid is substituted by valine. The individuals carrying the substitution on both β-chains (HbSS) develop the disease, characterized by chronic hemolytic anemia, systemic inflammatory state, and development of acute painful vaso-occlusive crises. Globally distributed, the disease has its highest incidence in sub-Saharan Africa (SSA), where its superimposes with the distribution of infections by parasitic worms, including schistosomes. However, there is scarcity of the literature on the possible interactions between parasitic worm infections and SCD. Schistosomes are parasitic worms responsible for the disease named schistosomiasis which affects over 240 million people in the world, of which over 90 % are found in SSA. The worms live within the blood vessels of infected individuals where females lay eggs which are strongly immunogenic, causing a systemic type 2 inflammation. The disease is characterized by anemia and the formation of granulomas in the liver and intestines (for Schistosoma mansoni & S. japonicum), leading to hepatic fibrosis, pulmonary hypertension, and hepatosplenomegaly. The overlapping of the clinical features of schistosomiasis and SCD highlights the existence of possible interactions between them in areas where they are both present. Leveraging the humanized mouse model of SCD, the aim of this study is to demonstrate how schistosome infection could affect the pathophysiology of SCD or vice versa. Methods Twenty-five - 28 weeks old male and female Townes (HbAA, HbAS, HbSS) were infected with S. mansoni . Complete blood count was performed before and 8 weeks after infection. Liver and small intestines (ileum) were chemically digested with 4% KOH and eggs counted in the suspension under a microscope. Fecal pellets were also collected and dispersed in 2x PBS and eggs were counted in the suspension as for liver and intestines. Data were analyzed with GraphPad Prism 9.5.1 software by using paired t-test or Wilcoxon test. Genotypes were compared by one-way ANOVA or Kruskall-Wallis tests followed by two-stage linear step-up procedure of Benjamini-Krieger-Yekutieli for the control of false discovery rate. Results Compared to HbAA and HbAS, which did not differ between them, naïve HbSS mice had bigger livers and spleens. This pattern remained even after infection, with infected HbSS having bigger livers and spleens than infected HbAA and HbAS. After the infection, the spleen size increased only in HbAA and HbAS but not in HbSS while liver size increased in all 3 genotypes. Schistosome infection caused a significant increase in the numbers of neutrophils, monocytes, eosinophils, and basophils. However, lymphocytes number significantly decreased in HbSS only. Red blood cells (RBCs) number decreased in HbAA and HbAS but not in HbSS. Accordingly, the mean corpuscular volume (MCV) and the mean corpuscular hemoglobin (MCH) increased in HbAA and HbAS, but not in HbSS. The Hb rate was not affected by the infection while the hematocrit slightly decreased only in HbAS. However, while the platelets number decreased only in HbSS, the mean platelet volume (MPV) increased in all 3 genotypes. HbSS mice had fewer total S. mansoni egg number than HbAA and HbAS. This trend was corroborated by the number of eggs in intestinal tissues in which HbSS had fewer eggs than HbAA and HbAS. Although the number of eggs in the liver did not differ significantly between them, HbSS tended to have fewer liver eggs than HbAA and HbAS. All 3 mouse groups excreted similar number of eggs in the feces. Conclusions All 3 genotypes of Townes mice supported the development of S. mansoni worms as illustrated by the presence of eggs in their liver, intestines, and feces, making this model a good model for the study of parasitic worm infections in SCD. Schistosome infection has affected less the RBC components in HbSS as shown by no changes in RBC, Hb, MCV, and MCH values, and by no change in the spleen size. Further investigations are underway.

Current Practice in Counseling about Sickle Cell Disease-Modifying Therapy and Sexual and Reproductive Health

Background: Sickle cell disease (SCD) is a genetic hematologic condition affecting individuals worldwide. Advances in therapy and management, including hydroxyurea, have reduced mortality. Clinicians who care for individuals with SCD face challenges in advising patients specifically about the impacts of hydroxyurea, a disease-modifying therapy (DMT), on sexual and reproductive health (SRH). There are currently no standard guidelines for clinicians on the risks and benefits of DMT regarding SRH. This study aims to characterize clinicians' current attitudes, practices, and barriers/facilitators to initiating and counseling around hydroxyurea use and SRH. Methods: In a cross-sectional qualitative study, we recruited clinicians caring for people with SCD from a national sample of American Society of Pediatric Hematology and Oncology members. Participants completed in-depth semi-structured interviews. Interviewers collected background information about the clinician and the nature of sickle cell care provided at their center. Topics included questions about clinicians' current practice in prescribing hydroxyurea and the counseling currently offered or the counseling they would like to provide regarding hydroxyurea and SRH. Interviews were transcribed verbatim and systematically coded using applied thematic analysis in NVivo. Results: 20 clinicians completed the interview (72% women, 78% White, 61% pediatrics-trained). Participants agreed that the benefits of decreased vaso-occlusive crises and mortality outweigh the risks of hydroxyurea to fertility. Participants also noted reduced morbidity, including decreased priapism frequency, which can lead to impotence and infertility, and reduced symptoms of dysmenorrhea. Participants concurred that counseling around hydroxyurea use varies by age, and no standard guidelines exist. When starting hydroxyurea in infants at nine months of age or at any time throughout childhood, clinicians noted that families are often hesitant at this stage to make decisions about their children that may affect their future. Families may not initiate discussions about their child's future fertility, but participants agreed that addressing the benefit and risks is essential. In contrast, clinicians reported that adolescents and young adults with SCD often direct the conversation themselves. The current practice for several participants is to continue hydroxyurea in most males or consider fertility assessment before recommending cessation of therapy, and only if they have had trouble conceiving. All participants agreed that the current practice is to take patients off hydroxyurea if they become pregnant, primarily based on teratogenicity risk and best practices from oncology. Some discussed restarting it later in pregnancy for disease control. Barriers to counseling were time constraints, limited data on whether fertility risks are related to the disease and/or the DMT, lack of standard guidelines on counseling, and sparse resource availability, including multi-disciplinary OB/GYN and genetic counseling support. Conclusion: Clinicians caring for people with SCD agree that hydroxyurea is a necessary DMT. However, clinicians also recognize the limited data and knowledge regarding the impacts of hydroxyurea on critical topics for individuals with SCD, including fertility and pregnancy. Healthcare providers who treat individuals with SCD should be aware of the unique SRH needs of this population. Further study is needed to identify patient attitudes regarding hydroxyurea and fertility risk and characterize current SRH counseling and practice in emerging disease-modifying therapies, gene therapy, and transplant.

A Phase 2/3, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study of Mitapivat in Patients with Sickle Cell Disease: RISE UP Phase 2 Results

Background: Sickle cell disease (SCD) is characterized by the presence of hemoglobin S (HbS), a structural variant caused by a mutation in the HBB gene. Deoxygenated HbS molecules polymerize into “fibers”, causing red blood cells (RBCs) to sickle and hemolyze. Sickled RBCs have a shortened lifespan and impede blood flow to tissues, causing painful vaso-occlusive crises. Recurrent microvascular damage and chronic hemolytic anemia result in progressive multi-organ damage. Mitapivat is an oral, small-molecule allosteric activator of pyruvate kinase, a key enzyme in RBC metabolism, with a dual mechanism of action under investigation in SCD: it increases adenosine triphosphate (ATP) in RBCs, improving survival, and decreases 2,3−diphosphoglycerate, increasing Hb oxygen affinity and thus diminishing HbS polymerization and RBC sickling. RISE UP is a global Phase (Ph) 2/3 double-blind, randomized, placebo (PBO)-controlled trial evaluating the efficacy and safety of mitapivat in patients (pts) with SCD (NCT05031780). Methods: In the Ph 2 double-blind period (DBP), 2 dose levels of mitapivat were evaluated against PBO for 12 weeks (wks). Eligible pts were ≥16 years with ≥5.5 to ≤10.5 g/dL Hb and ≥2 to ≤10 sickle cell pain crises (SCPCs, including pain, priapism, acute chest syndrome, hepatic sequestration, and splenic sequestration) in year prior to entry. Pts were randomized 1:1:1 to mitapivat 50 mg twice daily (BID), mitapivat 100 mg BID, or matched PBO. Pts completing the DBP were eligible to receive mitapivat in a 216-wk open-label extension. Primary endpoints were Hb response (≥1.0 g/dL increase in average Hb concentrations from Wks 10 through 12 compared with baseline [BL], tested with Fisher's exact test at 2-sided 0.05 significance level) and adverse events (AEs), including the type, severity, and relationship to study drug. Prespecified secondary endpoints included average change from BL from Wks 10 through 12 in Hb, markers of hemolysis, markers of erythropoiesis, and pt-reported fatigue score, as well as annualized rate of SCPCs. Results: In the Ph 2 DBP, 79 pts were randomized and treated with mitapivat 50 mg BID (n=26), mitapivat 100 mg BID (n=26), or PBO (n=27). In the 50 mg BID, 100 mg BID, and PBO arms, mean (SD) age was: 29.9 (7.79), 30.2 (10.52), and 28.5 (10.30) years; female: 57.7%, 61.5%, and 74.1%; mean (SD) BL Hb: 8.76 (1.295), 8.82 (0.898), and 8.49 (1.141) g/dL; mean (SD) number of SCPCs during previous year: 3.1 (1.83), 3.2 (1.65), and 3.4 (1.91), respectively. The primary endpoint was achieved; 46.2% (12/26) of pts in the 50 mg BID arm and 50.0% (13/26) in the 100 mg BID arm demonstrated a significant increase in Hb response compared with 3.7% (1/27) of pts in the PBO arm (2-sided p=0.0003 and p=0.0001, respectively). Mitapivat was generally well tolerated; observed safety profile was consistent with previously reported data of mitapivat in SCD and other hemolytic anemias. No serious treatment-emergent AEs were related to study drug; no AEs led to study drug discontinuation or death. Least-squares mean (LSM [95% CI]) for average change from BL in Hb levels from Wks 10 through 12 was 1.11 (0.77, 1.45) g/dL, 1.13 (0.79, 1.47) g/dL, and 0.05 (−0.28, 0.39) g/dL for 50 mg BID, 100 mg BID, and PBO arms, respectively ( Figure). Improvements were observed in markers of hemolysis and erythropoiesis. SCPCs annualized rates (95% CI) were 0.83 (0.34, 1.99) and 0.51 (0.16, 1.59) for 50 mg BID and 100 mg BID arms, respectively, compared to 1.71 (0.95, 3.08) for PBO. LSM (95% CI) for average changes from BL in pt-reported fatigue score from Wks 10 through 12 was −3.80 (−7.16, −0.45), −0.10 (−3.27, 3.08), and −0.17 (−3.40, 3.07) for 50 mg BID, 100 mg BID, and PBO arms, respectively ( Table). Conclusion: During the Ph 2 DBP of RISE UP, treatment with mitapivat demonstrated statistically significant and clinically meaningful improvement in Hb response at both dose levels (50 mg BID and 100 mg BID) compared to PBO. Improvements in markers of hemolysis/erythropoiesis and annualized rate of SCPCs were observed for both doses as compared with PBO; the magnitude of improvement in markers of hemolysis and annualized rate of SCPCs was larger in the mitapivat 100 mg BID arm. Mitapivat was well tolerated with a safety profile consistent with previous studies. These data suggest that mitapivat, through its dual mechanism of action, may provide clinical benefit to pts with SCD and support continued development in the Ph 3 portion of the RISE UP trial.

The Burden of Sickle Cell Disease on Children and Their Caregivers: Caregiver Reports of Children's Health-Related Quality of Life and School Experiences, Caregiver Burden, and Their Association with Frequency of Vaso-Occlusive Crises.

Children with sickle cell disease (SCD) experience a multiplex of disease-related symptoms and complications, including vaso-occlusive crises (VOCs), episodes characterized by extreme pain. A cross-sectional observational survey examined the health-related quality of life (HRQoL) and school experiences of children with SCD 2 months-11 years, burden experienced by their caregivers, and associations between these outcomes and VOC frequency. Caregivers (N=167) of children with SCD in the US completed the Infant-Toddler Quality of Life-Short Form 47 (ITQoL-SF47) for children 2 months-4 years, the Child Health Questionnaire-Parent Form 50 (CHQ-PF50) and PROMIS Pain Interference and Sleep Disturbance Parent Proxy short forms for children 5-11 years, and a study-specific survey of school experiences. Children with SCD 2 months-4 years had lower ITQoL-SF47 scores (ie, worse HRQoL, p<0.001) than a normative sample of children; across domains, differences ranged from 18.73-45.03 points and exceeded minimal important difference (MID) thresholds. Except for the behavior domain, children with SCD 5-11 years had lower scores on all CHQ-PF50 domains than the normative sample (p<0.001); differences ranged from 6.78-36.37 points and exceeded MID thresholds. Children with more frequent VOCs had lower HRQoL and worse school experiences than children with less frequent VOCs (p<0.05, except for behavior domains). The largest differences based on VOC frequency were observed for overall health and bodily pain/discomfort among children 2 months-4 years (differences=40.88 and 32.50 points, respectively), and bodily pain and role/social limitations due to physical health among children 5-11 years (differences=38.99 and 37.80, respectively). Caregivers of children with more frequent VOCs experienced greater burden than caregivers of children with less frequent VOCs, though specific areas of impact (eg, caregiver emotions, time) differed across child age groups. VOC frequency is negatively associated with HRQoL, highlighting the burden experienced by children with SCD and their caregivers.

Real-world evidence of the burden of sickle cell disease: a 5-year longitudinal study at a Brazilian reference center

IntroductionSickle cell disease (SCD) is an inherited and multisystem blood disorder characterized by hemolytic anemia, vaso-occlusive crises (VOCs), progressive multiorgan damage and increased mortality. In Brazil, it is one of the most common monogenic diseases afflicting 60,000 to 100,000 individuals, however, there are sparse epidemiological data, as well as information on the utilization of public healthcare resources. Method: This was a 5-year (2016 - 2020) retrospective study conducted at one Brazilian reference center on SCD - Santa Casa de Sao Paulo, in Sao Paulo, Brazil. ResultsAmong a total of 100 eligible adult patients, the median age was 31.0 years old, 84% of the patients were aged between 18 and 45 years old; 59% were women and 91% presented the genotype HbSS. The number of hematologist and non-hematologist visits at the outpatient unit were 2,198 and 1,436, respectively. The number of hospital ER visits was 758, of which 51% required 864 days of hospitalization. The main cause for seeking hospital medical care was the VOCs. The numbers and ratios of VOCs were: 1 to 10 VOCs, 64%; 11 to 20, 15%, and; 21 or more, 1%. There was a statistically significant difference between the number of VOCs and hospitalizations, as well as infection. Conclusion: Results indicate the burden of SCD on Brazilian patients’ daily lives, the impact of VOCs on public healthcare resources, the importance of having a national surveillance program to improve resource utilization and clinical outcomes of patients with SCD and the urgent need for the revitalizing of the current national comprehensive SCD care programs.

Frequency of Painful Crisis and Other Associated Complications of Sickle Cell Anemia Among Children.

Background Sickle cell disease (SCD) represents a group of inherited health conditions that affect red blood cells. SCD is a relatively common genetic disorder in Saudi Arabia, with the highest prevalence found in the Eastern Province region. The most common complications of SCD include acute chest syndrome, vaso-occlusive crisis, stroke, and avascular necrosis of the femoral head. The disease itself isnota cause of mortality but systemic complications are. Methodology In this retrospective study, we aimed to determine the frequency of painful crisis and the associated complications of sickle cell anemia (SCA) among children at King Saud Medical City (KSMC) in Riyadh, Saudi Arabia. Results This study included a total of 70 children with SCA below the age of 14 years who were admitted to KSMC from January 2021 to December 2021. Overall, 60% of the participants had one painful crisis attack per year, whereas 27% had two attacks. Furthermore, 94% of the participants were being treated with hydroxyurea. The most frequent cause of admission was painful crises with acute chest syndrome. Conclusions This study highlights the frequency of hydroxyurea use among SCA patients. Our results showed that participants who developed one to two painful crises per year were hospitalized for four to nine days on average with increased utilization of hydroxyurea.

Le globule rouge drépanocytaire : données fonctionnelles: The sickle red blood cell: functional data

Sickle cell anemia is a genetic disorder that affects hemoglobin leading to the production of an abnormal hemoglobin, called HbS. HbS has the property to polymerize under deoxygenated conditions, causing a mechanical distortion of red blood cells; a phenomenon called sickling. These sickle red blood cells are more fragile and rigid, leading to chronic hemolytic anemia and painful vaso-occlusive crises, as well as chronic vascular complications that can affect many organs. The abnormal functional properties of these sickle red blood cells are responsible for a wide range of clinical expression of the disease. HbS polymerization can be influenced by many factors, such as the hydration state of the red blood cells or the affinity of hemoglobin for oxygen. Moreover, the rheological characteristics of red blood cells, including their deformability and aggregation properties, are associated with specific clinical phenotypes. The pro-inflammatory and pro-oxidant state, as well as the repeated polymerization of HbS, accelerate the senescence of sickle red blood cells, promoting the release of microparticles and contributing to vascular dysfunction. Patients' red blood cells also have molecular characteristics that promote their adhesion to the endothelium and other circulating cells, contributing to the onset of vascular complications. Massive intravascular hemolysis, due to increased erythrocyte fragility, is also responsible for chronic vascular complications. These different alterations are privileged therapeutic targets, leading to the emergence of new specific treatments. © 2023 Société nationale française de médecine interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.

Stigma and patient-controlled analgesia: Trust is the essential ingredient of successful patient education in the patient-doctor relationship

A clinical decision report using: Van Beers EJ, Van Tuijn CFJ, Nieuwkerk PT, et al. Patient-controlled analgesia versus continuous infusion of morphine during vaso-occlusive crisis in sickle cell disease, a randomized controlled trial. Am J Hematol. 2007;82(11):955-960. https://doi.org/10.1002/ajh.20944 for a patient with recurrent vaso-occlusive crisis secondary to Sickle Cell Disease.

Liver Disease and Sickle Cell Disease: Auto-Immune Hepatitis more than a Coincidence; A Systematic Review of the Literature.

In patients with SCD, chronic liver damage is a common manifestation. More than 50% of SCD patients have elevated liver enzymes. Common underlying aetiologies include sickle cell hepatic crisis, viral hepatitis, sickle cell intrahepatic cholestasis and hepatic sequestration in the acute setting, and cholelithiasis and iron overload in the chronic setting. Autoimmune hepatitis (AIH) is a rare disease that appears to occur more commonly in the sickle cell disease (SCD) population than in the general population. There are many schools of thought as to why this is the case, including the phosphatidylserine hypothesis, the heme inflammatory hypothesis, the complement generation hypothesis, and the transfusion alloimmunization hypothesis. Due to the natural history of the two illnesses, SCD is almost always diagnosed first in cases of dual pathology. Symptoms such as jaundice, fatigue, and abdominal pain are common in SCD, as are abnormal liver function tests (LFTs). These abnormalities, attributed to the other more frequent liver involvements in SCD, can lead to delays in AIH diagnosis in this population. Corticosteroids, sometimes with other immunosuppressive agents, such as azathioprine, are the cornerstone of acute AIH treatment. However, corticosteroid use in the SCD population has been shown to carry an increased risk of vaso-occlusive crises, providing a treatment dilemma. The following is a review of AIH in the SCD population, where we explore the pathophysiology behind the association between the two disorders, discuss an approach to investigating abnormal LFTs in SCD, and examine treatment options in this population with co-existing diseases.

Use of consumer wearables to monitor and predict pain in patients with sickle cell disease.

In sickle cell disease (SCD), unpredictable episodes of acute severe pain, known as vaso-occlusive crises (VOC), disrupt school, work activities and family life and ultimately lead to multiple hospitalizations. The ability to predict VOCs would allow a timely and adequate intervention. The first step towards this ultimate goal is to use patient-friendly and accessible technology to collect relevant data that helps infer a patient's pain experience during VOC. This study aims to: (1) determine the feasibility of remotely monitoring with a consumer wearable during hospitalization for VOC and up to 30 days after discharge, and (2) evaluate the accuracy of pain prediction using machine learning models based on physiological parameters measured by a consumer wearable. Patients with SCD (≥18 years) who were admitted for a vaso-occlusive crisis were enrolled at a single academic center. Participants were instructed to report daily pain scores (0-10) in a mobile app (Nanbar) and to continuously wear an Apple Watch up to 30 days after discharge. Data included heart rate (in rest, average and variability) and step count. Demographics, SCD genotype, and details of hospitalization including pain scores reported to nurses, were extracted from electronic medical records. Physiological data from the wearable were associated with pain scores to fit 3 different machine learning classification models. The performance of the machine learning models was evaluated using: accuracy, F1, root-mean-square error and area under the receiver-operating curve. Between April and June 2022, 19 patients (74% HbSS genotype) were included in this study and followed for a median time of 28 days [IQR 22-34], yielding a dataset of 2,395 pain data points. Ten participants were enrolled while hospitalized for VOC. The metrics of the best performing model, the random forest model, were micro-averaged accuracy of 92%, micro-averaged F1-score of 0.63, root-mean-square error of 1.1, and area under the receiving operating characteristic curve of 0.9. Our random forest model accurately predicts high pain scores during admission for VOC and after discharge. The Apple Watch was a feasible method to collect physiologic data and provided accuracy in prediction of pain scores.

Serum cardiac troponin I levels in adults with sickle cell disease visiting the University College Hospital, Ibadan, Nigeria

Abstract significant association between troponin I level in&#x0D; &#x0D; Recurrent vaso-occlusive crisis and haemolysis normally affect the lifestyle of patients with sickle cell disease. This may occur for a few hours or some weeks, making many of them to require hospital admission and blood transfusion, with inevitable financial implications on care givers. Due to its tissue specificity, cardiac troponin I and T have been claimed to be important in detecting cardiac damage even in the presence of elevated total creatine kinase (CK) and CK-MB that can likely occur in exercise-induced skeletal muscle damage. The significance of cardiac assessment in sickle cell patients was emphasized in a previous report which showed that evidence of mortality related to cardiovascular causes was often encountered during autopsy. This study aimed at accessing serum cardiac Troponin I (cTnI) in adult patients with sickle cell disease at University College Hospital, Ibadan. After written consents were obtained, 131 individuals above 18 years were recruited, 95 of which were sickle cell disease subjects and 36 were non-sickle cell disease controls. Mean age was 35.4years±SD=7.54years with age range of 19 to 56years for the sickle celled subjects and 36.8years±SD=9.11years with age range of 19 to 58 years for controls. Male to female ratio was approximately 2:1 for control and 2.4 :1 for sickle cell subjects. A total of 4(4.2%) sickle cell patients had abnormal troponin I level. There was a significant difference in mean troponin I level between sickle cell subjects and control, but there was no significant association between troponin I and haematological parameters of the sickle cell patients. The likelihood of the sickle cell subjects developing crisis is low, but there was no significant association significant association between troponin I level in sickle cell subjects and their haematological parameters, while there was a significant difference in mean troponin I between Sickle cell subjects and non-Sickle cell controls.

Case Report of Numb Chin Syndrome (NCS) in Sickle Cell Disease (SCD)

Numb chin syndrome is a rare presentation due to injury to mental nerve characterized by numbness, hypoesthesia, and paresthesia. This syndrome is mostly presented with dental interventions, traumatic injuries, or malignant pathologies. We report a unique case of a 20-year-old male diagnosed with sickle cell disease presented with loss of sensation over right chin area secondary to the vaso-occlusive crisis. This case depicts a complex relationship between neurological complications and hemoglobinopathies of SCD.

Functional near-infrared spectroscopy-based prefrontal cortex oxygenation during working memory tasks in sickle cell disease.

Sickle cell disease (SCD), characterized by painful vaso-occlusive crises, is associated with cognitive decline. However, objective quantification of cognitive decline in SCD remains a challenge, and the associated hemodynamics are unknown. To address this, we utilized functional near-infrared spectroscopy (fNIRS) to measure prefrontal cortex (PFC) oxygenation responses to -back working memory tasks in SCD patients and compared them with healthy controls. We quantified the PFC oxygenation rate as an index of cognitive activity in each group and compared them. In half of the participants, a Stroop test was administered before they started -back to elevate their baseline stress level. In SCD compared to healthy controls, we found that (1)under a high baseline stress level, there were significantly greater oxygenation responses during the 2-back task, further elevated with histories of stroke; (2)there was a marginally slower -back response time, and it was even slower with a history of stroke; and (3)the task accuracy was not different. Additional requirements for processing time, PFC resources, and PFC oxygenation in SCD patients offer an important basis for understanding their cognitive decline and highlight the potential of fNIRS for evaluating cognitive functions.

A Newborn Screening Program for Sickle Cell Disease in Murcia (Spain).

Sickle cell disease (SCD) is an inherited autosomal recessive hemoglobin disorder caused by the presence of hemoglobin S, a mutant abnormal hemoglobin caused by a nucleotide change in codon 6 of the β-globin chain gene. SCD involves a chronic inflammatory state, exacerbated during vaso-occlusive crises, which leads to end-organ damage that occurs throughout the lifespan. SCD is associated with premature mortality in the first years of life. The process of sickling provokes asplenia in the first years of life with an increased risk of infection by encapsulated germs. These complications can be life-threatening and require early diagnosis and management. The most important interventions recommend an early diagnosis of SCD to ensure that affected newborns receive immediate care to reduce mortality and morbidity. The newborn screening program in the region of Murcia for SCD began in March 2016. We aimed to determine the incidence of sickle cell anemia and other structural hemoglobinopathies in the neonatal population of the region of Murcia, an area of high migratory stress, and to systematically assess the benefit of newborn screening for SCD, leading to earlier treatment, as well as to offer genetic counseling to all carriers. The prevalence of SCD in our region is similar to others in Spain, except for Catalonia and Madrid. The newborns with confirmed diagnoses of SCD received early attention, and all the carriers received genetic counseling.

270 Appropriate Emergency Severity Index Assignment and Timely Pain Management for Emergency Department Patients With Vaso-occlusive Crisis

270 Appropriate Emergency Severity Index Assignment and Timely Pain Management for Emergency Department Patients With Vaso-occlusive Crisis

CTH1/TH2 repolarization in induction of immune tolerance to non-steroidal anti-inflammatory drugs during the management of sickle cell disease vaso-occlusive crisis

Respiratory manifestations related to the intake of non-steroidal anti-inflammatory drugs (NSAIDs) during the treatment of the painful vaso-occlusive crisis of sickle cell disease are either a type I hypersensitivity mechanism of the Gell and Coombs classification, or a pharmacological mechanism of NSAIDs. The use of NSAIDs is essential in the Abidjan school because of the absence of therapeutic alternatives in the management of the inflammatory crisis of this disease. The induction of tolerance to NSAIDs initiated by the authors has had clear clinical success. The basic biological reasons for this tolerance were evaluated in this study. A group of 11 sickle cell patients aged 12 to 39 years in whom post-NSAID respiratory manifestations disappeared for at least 6 months following a short tolerance induction protocol with ibuprofen, was assayed by ELISA for TNFα, INFg (Th1 cytokines), IL-4 (Th2 cytokine), IL-10, TGF-β (immunosuppressive cytokines) and total IgE, before induction or pre-induction (D-1) and at day one (D1), D2- 3, one month (M1), and M6 after induction. A repolarization of the Th1/Th2 balance was noted during the post induction period. The high concentration of IL-4 observed at D-1 gradually decreased in favor of the cytokines TNFα, INFg. The decrease in cytokine IL-4 with the level of total IgE was accompanied by the increase of IL-10 and TGF-β demonstrating the regulatory role of these cytokines in the control of allergic diseases. In conclusion, the induction of immuno-tolerance to NSAIDs through a short protocol is well supported by immune regulation. The medium-term effects are real, unlike the results of allergen desensitization or specific immunotherapy. However, this protocol could be used in certain circumstances such as in the case of intolerance to trimethoprim-sulfamethoxazole, used as the treatment of choice for the prevention of opportunistic diseases in people living with human immunodeficiency virus.

Crizanlizumab in sickle cell disease.

Vaso-occlusion in sickle cell disease (SCD) leads to a myriad of manifestations driving morbidity and mortality in patients with SCD. Increased leucocyte adhesion and P-selectin expression on platelets and endothelial cells is an inciting eventthat leads to obstruction of microcirculation by adhesion with rigid sickled red blood cells. Crizanlizumab is a first-in-class monoclonal antibody that inhibits P-selectin and has been shown to decrease the frequency of vaso-occlusive pain crises in patients with SCD in clinical trials. The role of crizanlizumab in other manifestations of SCD still needs further investigation.

The impact of interferon-gamma level on the health status of patients with sickle cell disease in Basrah

Sickle cell disease (SCD) is one of the most prevalent autosomal recessive diseases, characterized by the generation of abnormal hemoglobin S. Our study aimed to assess how the serum level of interferon-gamma affects the health status of patients with SCD in Basrah. A total of 90 participants were enrolled in this study and divided into two main groups: a SCD group and a control group. The SCD group included 30 patients with SCD in steady state and 30 patients with SCD in vasoocclusive crisis; the control group included 30 ageand sexmatched apparently healthy individuals. Approval was obtained from the Research Ethics Committee of the College of Medicine, University of Basrah before conducting the study. Two milliliters of venous blood were drawn from all the participants, and ELISA tests were utilized to determine the levels of serum interferon-gamma. There was a statistically significant increase in the serum level of interferon-gamma among SCD patients (both in steady state and in crisis) compared to the control group (p = 0.05). There were no significant differences in the levels of interferon-gamma between the patients in steady state and during vaso-occlusive crisis (p &gt; 0.05). Interferon-gamma may influence the general health of sickle cell patients and contribute to the cause of inflammation, no matter whether the patient is in stable condition or is experiencing a crisis.

Associated Factors of Cholelithiasis among Younger Children with Sickle Cell Disease at the National Reference Center for Sickle Cell Disease in Brazzaville, Congo.

Chronic hemolysis predisposes sickle cell patients to the development of gallstones. Their frequency increases with age, but they may appear early in young children. In the absence of management, they expose the patient to complications that can hinder the quality of life and sometimes even death. This survey aimed to identify the associated factors of the occurrence of cholelithiasis. It was a case-control study carried out between January 2017 and June 2022 at the National Reference Center for Sickle Cell Disease (SCD) "Antoinette Sassou N'guesso" in Brazzaville. It concerned 37 children with cholelithiasis. Sociodemographic (socioeconomic status and diet) and clinical (body mass index, frequency of vasoocclusive crises and hospitalization for vasoocclusive crises, number of blood transfusion, and chronic complications) as well as hematological examination (type of SCD and blood count in the intercritical period) and hydroxyurea treatment were compared with those of 74 children with no clinical and radiographic signs of cholelithiasis. The chi-squared statistical test and the odds ratio were used for the comparison (p < 0.05). The average age was 9.70 ± 1.73 years. The 10-12 age group was the most represented (22 cases or 59.45%), followed by 7- to 9-year-olds (12 cases or 32.43%). Three children (8.10%) were 6 years old. The sex ratio was 0.68 vs. 1.38. Factors associated with cholelithiasis were low socioeconomic status (83.78% vs. 45.95%; IC 95% 1.46-3.89; p ≤ 0.001), a higher number of blood transfusions (5.54 ± 1.22 vs. 2.46 ± 1.13; IC 95% 1.55-6.70; p ≤ 0.001), and irregular systematic monitoring (5.54 ± 1.22 vs. 2.46 ± 1.13; IC 95% 1.55-6.70; p ≤ 0.001). A national strategy to facilitate access to care for patients living with sickle cell disease is imperative. Moreover, emphasis should be placed on the prevention and early management of acute complications of SCD.

Impact of hospitalization for vaso-occlusive crisis on health-related quality of life in children with sickle cell disease.

Sickle cell disease (SCD) is characterized by vaso-occlusive crises (VOCs) that impair the health-related quality of life (HRQoL). The aim of this study is to evaluate the impact of hospitalization for VOCs on HRQoL in children with SCD over time. In this longitudinal cohort study, children aged 8-18years diagnosed with SCD at the Amsterdam UMC were included between 2012 and 2021. HRQoL was annually measured as part of standard care using the Pediatric Quality of Life Inventory. The impact of hospitalization for VOC on HRQoL was evaluated using linear mixed models 3, 6, 9, and 12months after hospitalization. The effect of frequency of hospitalization for VOC on HRQoL was evaluated over the last 12months. In total, 94 children with SCD were included with a median age of 11.8years (interquartile range [IQR]: 9-14). Thirty-seven patients (39%) had been hospitalized for a VOC. Hospitalization for VOC led to a decrease of 3.2-4.8 points in total HRQoL compared to patients without hospitalization, most pronounced 3months after hospitalization. Recurrent admission for VOC in the last 12months was associated with a decrease of 2.3 points in total HRQoL (p=.04). The most affected subscale was physical functioning. The adverse effects of hospitalization for VOC in children with SCD persist up to 12months after hospitalization. After hospitalization for VOC, extra attention and support for its negative impact on HRQoL are recommended. This study also underlines the importance of systematically measuring HRQoL, allowing clinicians to intervene accordingly.