Acute Chest Syndrome Research Articles

Pubertal patterns in children with sickle cell anemia: A case–control study in Cameroon

BackgroundPuberty may be impaired in children with sickle cell anemia (SCA). Therefore, we aimed to explore the clinical and hormonal features of puberty in Cameroonian children. MethodsIn a case–control study, we included 64 children aged 8–18 years with SCA matched to healthy controls. We assessed height, weight, body mass index, body composition, and Tanner stages. Hormonal measurements included anti-mullerian hormone, follicle-stimulating hormone, luteinizing hormone, and sex hormones (estrogens/testosterone). We used the Mann–Whitney Wilcoxon test to compare the median values between cases and controls. We looked for associations between the severity criteria of SCA and delayed puberty through multivariate analysis. ResultsDelayed puberty was reported in 27.3% of girls and 10% of boys with SCA. The median age of menarche was delayed by 2 years compared to controls. SCA patients had a low lean body mass compared to controls (p = 0.03). Anti-mullerian hormone levels were significantly higher in boys with SCA than those of controls (45.9 ng/mL vs. 17.65 ng/mL; p = 0.018). A history of severe infection, acute chest syndrome, and low hemoglobin level was associated with delayed sexual maturation in children with SCA. ConclusionOur study revealed delayed puberty in children with SCA. Moreover, puberty is affected by the severity of the disease. This highlights the importance of regular monitoring of puberty during the follow-up of these children.

Evaluation of a prophylactic transfusion program on obstetric outcomes in pregnant women with sickle cell disease: A single centre retrospective cohort study

ObjectiveTo evaluate the effects of a prophylactic transfusion program (TP) on obstetric and perinatal outcomes in pregnant women with sickle cell disease (SCD). MethodsThis retrospective cohort study included all singleton pregnancies among women with SCD in a French university tertiary care center between 1 January 2004 and 31 December 2017. The TP group included patients selected according to the French guidelines who received regular red blood cell transfusions during pregnancy until delivery. The factors associated with TP indication [year of birth, SCD genotype, history of acute chest syndrome and delayed hemolysis transfusion reaction (DHTR) risk score] were taken into account in a propensity score. A composite obstetric adverse outcome was defined associating birth before 34 gestational weeks and/or pre-eclampsia and/or small for gestational age and/or abruption and/or stillbirth and/or maternal death and/or neonatal death. ResultsIn total, 246 pregnancies in 173 patients were analyzed. Twenty-two pregnancies with a history of DHTR were excluded. A higher frequency of TP was found before 2013 [119/148 (80.4%) vs 38/76 (50%); p < 0.001]. Rates of preterm birth before 34 gestational weeks (5.6% vs 19.7%; p = 0.001), vaso-occlusive crisis (36.5% vs. 61.8%; p < 0.001), and acute chest syndrome (6.1% vs. 14.5%; p = 0.04) during pregnancy were decreased significantly in the TP group. Among the groups with and without composite obstetric adverse outcomes, the frequency of TP was 52.6% and 74.7%, respectively [odds ratio (OR) 0.30, 95% confidence interval (CI) 0.09–1.02]. The multivariate analysis shows that the TP was associated with a significant reduction in the risk of composite obstetric adverse outcomes (OR 0.28, 95% CI 0.08–0.97; p = 0.04). ConclusionA red blood cell TP may have an independent protective effect on maternal and perinatal adverse outcomes during pregnancy in women with SCD.

Associating a standardized reporting tool for chest radiographs with clinical complications in pediatric acute chest syndrome.

Acute chest syndrome (ACS) is an important cause of morbidity in sickle cell disease (SCD). A standardized tool for reporting chest radiographs in pediatric SCD patients did not previously exist. To analyze the interobserver agreement among pediatric radiologists' interpretations for pediatric ACS chest radiographs utilizing a standardized reporting tool. We also explored the association of radiographic findings with ACS complications. This was a retrospective cohort study of pediatric ACS admissions from a single institution in 2019. ICD-10 codes identified 127 ACS admissions. Two radiologists independently interpreted the chest radiographs utilizing a standardized reporting tool, a third radiologist adjudicated discrepancies, and κ analysis assessed interobserver agreement. Clinical outcomes were correlated with chest radiograph findings utilizing Pearsons' χ2 , ttests, and Mann-Whitney U tests. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Interobserver agreement was moderate to near-perfect across variables, with κ analysis showing near-perfect agreement for opacity reported in the right upper lobe (0.84), substantial agreement for right lower lobe (0.63), and vertebral bony changes (0.72), with moderate agreement for all other reported variables. On the initial chest radiograph, an opacity located in the left lower lobe (LLL) correlated with pediatricintensive care unit transfer (p = .03). Pleural effusion on the initial chest radiograph had a 3.98 OR (95% CI: 1.35-11.74) of requiring blood products and a 10.67 OR (95%CI: 3.62-31.39) for noninvasive ventilation. The standardized reporting tool showed moderate to near-perfect agreement between radiologists. LLL opacity, and pleural effusion were associated with increased risk of ACS complications.

Acute chest syndrome in children with sickle cell disease: Data from a national AIEOP cohort identify priority areas of intervention in a hub-and-spoke system.

Acute chest syndrome (ACS) is a frequent cause of hospitalization in sickle cell disease (SCD). Despite advances in acute care, many settings still lack knowledge about ACS best practices. After the AIEOP Guidelines were published in 2012, suggesting standardized management in Italy, a retrospective study was performed to assess the diagnostic and therapeutic pathways of ACS in children. From 2013 to 2018, 208 ACS episodes were presented by 122/583 kids in 11 centres. 73 were male, mean age 10.9 years, 85% African, 92% HbSS or Sβ°. In our hub-and-spoke system, a good adherence to Guidelines was documented, but discrepancies between reference centres and general hospitals were noted. Improvement is needed for timely transfer to reference centres, use of incentive spirometry, oxygen therapy and pain management.

Hospitalizations among children with sickle cell disease enrolled in the Kumasi Sickle Cell Pan African Consortium (SPARCo) database: A cross sectional study.

Sickle cell disease (SCD) is the commonest monogenic haemolytic disorder in Africa. Despite strides made in its management, a significant proportion of patients are hospitalized from the various complications of the disease. This study set out to describe the main causes and outcomes of hospitalizations among pediatric patients with SCD. A cross-sectional study was conducted at the Pediatric Emergency Unit of Komfo Anokye Teaching Hospital within a period of 12 months to recruit pediatric SCD patients. This study looked at causes of admission, length of hospital stay (LOS), and outcome of admission. Of the 201 SCD patients recruited, 57.2% were males and majority were of SCD-SS phenotype 83.1%. The median age was 6 years. The three leading causes of hospitalization were Vaso-occlusive pain events (VOPE) (39.8%), acute chest syndrome (ACS) (25.9%), and infections (12.4%). Ten (5.0%) of the patients presented with a stroke. High admissions were observed in June (12.4%) and November (16.9%). The median (interquartile range [IQR]) LOS was 6 days (IQR: 4-10). Six (3.0%) of the patients died from complications of the disease during hospitalization. VOPE, ACS, infections, and acute anaemia from hyperhaemolysis were observed as the most common causes of admissions among SCD patients. A good outcome of discharge was seen in most of the patients that were hospitalized with a median length of stay of 6 days. This study also strengthens the importance of a good SCD database with patient follow-ups for better outcomes in SCD patients.

Unique Changes in the Incidence of Acute Chest Syndrome in Children With Sickle Cell Disease Unravel the Role of Respiratory Pathogens: A Time Series Analysis

Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD). Although respiratory pathogens are frequently detected in children with ACS, their respective role in triggering the disease is still unclear. We hypothesized that the incidence of ACS followed the unprecedented population-level changes in respiratory pathogen dynamics after COVID-19-related nonpharmaceutical interventions (NPIs). What is the respective role of respiratory pathogens in ACS epidemiology? This study was an interrupted time series analysis of patient records from a national hospital-based surveillance system. All childrenaged < 18 years with SCD hospitalized for ACS in France between January 2015 and May 2022 were included. The monthly incidence of ACS per 1,000 children with SCD over time was analyzed by using a quasi-Poisson regression model. The circulation of 12 respiratory pathogens in the general pediatric population over the same period was included in the model to assess the fraction of ACS potentially attributable to each respiratory pathogen. Among the 55,941 hospitalizations of children with SCD, 2,306 episodes of ACS were included (median [interquartile range] age, 9 [5-13] years). A significant decrease was observed in ACS incidence after NPI implementation in March 2020 (-29.5%; 95%CI, -46.8 to -12.2; P= .001) and a significant increase after lifting of the NPIs in April 2021 (24.4%; 95%CI, 7.2 to 41.6; P= .007). Using population-level incidence of several respiratory pathogens, Streptococcus pneumoniae accounted for 30.9%(95%CI, 4.9 to 56.9; P= .02) of ACS incidence over the study period and influenza 6.8%(95%CI, 2.3 to 11.3; P= .004); other respiratory pathogens had only a minor role. NPIs were associated with significant changes in ACS incidence concomitantly with major changes in the circulation of several respiratory pathogens in the general population. This unique epidemiologic situation allowed determination of the contribution of these respiratory pathogens, in particular S pneumoniae and influenza, to the burden of childhood ACS, highlighting the potential benefit of vaccine prevention in this vulnerable population.

Education Liaison improves implementation of school accommodations for students with sickle cell disease.

Children with sickle cell disease (SCD) have lower academic attainment than healthy peers. Many benefit from neuropsychological testing (NPT) and educational accommodations, including Individualized Education Programs (IEPs) and Section 504 plans (504s). Despite medical barriers to academic attainment, many children with SCD do not receive indicated NPT or accommodations. We hypothesize that a dedicated Education Liaison (EL) embedded in the SCD team increases implementation of NPT and accommodations. This retrospective study included children aged 5-20years with SCD receiving care at a single center from 2017 through 2020. Univariate analysis and multiple logistic regression were performed. Total 316 children with SCD were included. At baseline, 52.8% had accommodations (IEP: 24.4%, 504: 38.0%). The EL interacted with 62.0% of children. Children with EL contact were more likely to undergo NPT (odds ratio [OR]: 5.385), have an IEP (OR: 4.580), and have a 504 (OR: 2.038) (p<.001 for all). At the end of the study period, 64.6% had accommodations (IEP: 33.5%, 504: 54.4%), which increased from baseline (p<.001 for all). EL interaction was associated with overt or silent stroke history (OR: 1.911), acute chest syndrome history (OR: 2.257), hospitalizations since age 5 (OR: 3.216), and hospitalization for vaso-occlusive pain since age 5 (OR: 2.226) (p<.001 for all). EL interaction improves access to NPT and educational accommodations among children with SCD. SCD centers should incorporate ELs in comprehensive care teams to improve access to appropriate educational accommodations.

The Role of Non-genetic Therapies to Reduce the Incidence of Sickle Cell Crisis: A Systematic Review.

Sickle cell anemia is a hemoglobinopathy that causes complications such as Vaso-Occlusive Crisis (VOC), stroke, priapism, Acute Chest Syndromes (ACS), and bone infarcts due to blood vessel occlusion, resulting in hypoxia, ischemia, and inflammation. Preventing these incidents improves the quality of life and lowers mortality rates in Sickle Cell Disease (SCD) patients. This systematic review aims to describe the drugs, their mechanisms of action, dosages, changes in hemoglobin parameters, decrease in VOCs, delay the time for the next VOC, decrease in the length of hospital stay, and side effects associated with these drugs. This review adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines. For this review, we searched the PubMed, Google Scholar, and Cochrane databases and screened them for full free texts published in English and studied in humans in the last five years beginning in 2018. Randomized clinical trials (RCT), observational studies, meta-analyses, systemic reviews, and traditional reviews were all included in the search. According to the type of study, quality assessment tools are used, and eight papers are chosen. Full-text articles from these papers are studied, analyzed, and tabulated. We discussed seven interventions that are used to treat sickle cell disease. Voxelotor, crizanlizumab, L-glutamate, long-term blood transfusions, Zinc (Zn), Niprisan®, and Ciklavit* were found to reduce the number and severity of VOC. We discovered that VOCs containing L -glutamate reduced the length of hospitalization. Magnesium (Mg) did not affect the number and severity of VOCs. This review includes a few articles for the study. Future papers on this subject should include a large sample size and many papers. More clinical trials are required to evaluate the dosages and outcomes of using these drugs in combination to prevent VOCs.

IMPACT OF COVID-19 ON SICKLE CELL DISEASE PATIENTS A NARRATIVE REVIEW

Objective:Thereviewaimedto examine the evidencefortheimpactofCOVID-19onSickleCellDisease(SCD) patients. Background: Coronavirusdisease (COVID-19) continues to ravage various parts of the world, with increasing cases of morbidity and mortality. The coronavirus primarily targets therespiratory system, although it affects other organs. Evidence shows that patients with pre-existingconditions, suchas SCD,areato higherriskofdevelopingsevereCOVID-19illness anddeath. Methods:Anarrativereview wasconductedthroughacomputerizedsearchonthePubMeddatabase.Tenarticlesmettheinclusioncriteriaandwereincludedinthesynthesis. Discussion:Thefindings ofthereview showthatSCD patientsareatincreasedriskofsevereillnessanddeathwheninfectedwithCOVID-19duetotheirimmunocompromisedstate. Although there is heterogenicity in results, most studies concur that SCD complications such asVaso-occlusive crisis (VOC), Acute Chest Syndrome (ACS), stroke, and acute anemia pose thegreatestriskofmorbidityandmortality.However,mostpatientsshowfavorableoutcomeswhenprovidingwith properintervention. Conclusion:Basedonthefindingsofthisreview,patientswithSCDhavesignificantlyadverseCOVID-19outcomes.

Long-term clinical outcomes and healthcare utilization of sickle cell disease patients with COVID-19: A 2.5-year follow-up study.

This study investigated whether patients with sickle cell disease (SCD) had elevated risk of worse long-term clinical outcomes and healthcare utilization 2.5 years post-SARS-CoV-2 infection. This study consisted of 178 patients with SCD who tested positive for COVID-19 between February 1, 2020 and January 30, 2022 in a major academic health system in New York City. The control cohort consisted of two-to-one matches of 356 SCD patients without a COVID-19 positive test. The last follow-up was July 18, 2022. The primary outcome was mortality. Secondary outcomes were annualized emergency department visits due to pain, pain hospital admission, length of stay due to pain, acute chest syndrome, episodic transfusion, and episodic exchange transfusion. There was no significant difference in mortality between SCD patients with and without COVID-19 (p > .05). There were no significant differences in secondary outcomes between pre- and postpandemic (p > .05). There were also no significant differences in these outcomes between SCD patients with and without COVID-19 (p > .05). SCD care utilization was not significantly associated with COVID-19 hospitalization status (p > .05). SCD patients with SARS-CoV-2 infection incurred no additional risk of worse long-term outcomes compared to matched controls of SCD patients not infected by SARS-CoV-2.

Evaluation of Intestinal Microbiota in Children With Sickle Cell Disease.

Sickle cell disease (SCD) is a chronic hemolytic anemia that may be life-threatening due to multisystemic effects. Identification of the factors which affect the pathophysiology of the disease is important in reducing mortality and morbidity. This study aimed to determine gut microbial diversity in children and adolescents with SCA compared with healthy volunteers and to evaluate the clinical impact of microbiota. The study included 34 children and young adolescents with SCD and 41 healthy volunteer participants. The microbiome was assessed by 16S rRNA sequencing in stool samples. Laboratory parameters of all participants, such as complete blood count and C-reactive protein values and clinical characteristics of SCD patients, were determined and compared, as well as clinical conditions of the patients, such as vascular occlusive crisis and/or acute chest syndrome, frequency of transfusions, intake of penicillin, hydroxyurea, and chelation therapy were recorded. White blood cell count, hemoglobin, immature granulocyte and C-reactive protein levels were significantly higher in the patient group ( P <0.05). Microbiota analysis revealed 3 different clusters among subjects; controls and 2 clusters in the SCD patients (patient G1 and G2 groups). Bacteroides spp. were more prevalent, while Dialester spp. and Prevotella spp. were less prevalent in SCD compared with controls ( t =2.142, P <0.05). Patient G2 (n=9) had a higher prevalence of Bacteroides and a lower prevalence of Prevotella than patient G1 (n=25). In our study, there was a difference between SCD patients and the control group, while 2 different microbiota profiles were encountered in SCD patients. This difference between the microbiota of the patients was not found to affect the clinical picture (such as vascular occlusive crisis, acute chest syndrome).

Contemporary Obstetric and Neonatal Outcomes in Sickle Cell Disease: A Retrospective Cohort Study.

Sickle cell disease is associated with adverse perinatal outcomes. Aspects of sickle cell disease in pregnancy, such as health care utilization and neonatal abstinence syndrome, are understudied. We aimed to describe contemporary sickle cell disease outcomes in a U.S. hospital system to improve perinatal counseling. We conducted a retrospective cohort study of patients with sickle cell disease who delivered at >20 weeks' gestation at two sites within the University of Pennsylvania Health System from May 1, 2017 to August 30, 2020. Descriptive statistics were utilized. Over the study period, 48 patients with sickle cell disease had 52 deliveries of 53 neonates. Sickle cell disease-related morbidity was prevalent prior to pregnancy; 27% had a history of avascular necrosis, and 58% had experienced acute chest syndrome. In the year prior to pregnancy, 52% used daily opioids. During pregnancy, more than half of patients were admitted at least once for sickle cell disease-related complications, spending a median 3 days admitted interquartile range (0-23); >10% spent >70 days of pregnancy admitted. New daily opioids were prescribed during pregnancy for 10% to manage pain crises. Acute chest syndrome was experienced by 23% of patients during pregnancy, and 8% required placement of long-term intravenous access. Preterm delivery <37 weeks occurred in 48%. The primary cesarean rate in nulliparas was 43%. Additionally, 50% experienced a hypertensive disorder of pregnancy, 35% underwent transfusion during delivery admission, and 10% had a perinatal venous thromboembolism. Finally, 53% of neonates were admitted to the intensive care unit. Low birth weight was noted in 34%, severe respiratory distress in 15% of infants, and neonatal abstinence syndrome in 21%. Sickle cell disease remains associated with significant perinatal morbidity and need for hospitalization. These data provide contemporary outcomes to target improvements in the care of patients with sickle cell disease. · SCD was associated with significant perinatal morbidity and healthcare utilization.. · Most patients with SCD required hospitalization during pregnancy.. · Neonates of patients with SCD experienced preterm birth, NICU admission, and neonatal abstinence syndrome..

The Role of Antiplatelet in the Management of Sickle Cell Disease Patients.

Sickle cell disease (SCD) is a genetic disorder characterized by abnormal hemoglobin, leading to red blood cell deformities and subsequent vaso-occlusive events. Platelet activation and adhesion play a significant role in the pathophysiology of SCD, contributing to the development of complications such as vaso-occlusive events, stroke, acute chest syndrome, and other manifestations. Antiplatelet therapy has emerged as a potential strategy to mitigate these complications by modulating the platelet function and reducing thrombotic events. This review article provides an overview of antiplatelet therapy's role in managing SCD patients. It discusses the pathophysiological abnormalities in the platelet function in SCD, the rationale for antiplatelet therapy, and the evidence supporting its use in various clinical scenarios. The article explores aspirin as the primary antiplatelet agent in SCD, including its mechanism of action, dosing considerations, and efficacy and safety data. Additionally, it highlights other antiplatelet agents, such as clopidogrel, prasugrel, ticagrelor, and emerging therapies under investigation. Clinical applications of antiplatelet therapy in primary and secondary prevention and the management of acute chest syndrome and other SCD complications are also discussed. Safety considerations are emphasized, including bleeding risk assessment, monitoring, and patient selection for antiplatelet therapy. Finally, the review highlights future research and clinical practice directions, including the development of novel antiplatelet agents, combination therapies, and the integration of antiplatelet therapy with other SCD treatments. Overall, this review provides a comprehensive understanding of the current role of antiplatelet therapy in SCD management, the challenges faced, and future directions for improving patient outcomes.

Is Hydroxyurea Treatment Changing the Life of Children with Sickle Cell Disease?

Background: Sickle cell disease (SCD) is a prevalent hemoglobinopathy involving sickled hemoglobin that causes multiorgan disease due to chronic recurrent vaso-occlusion and hemolysis. Fetal hemoglobin (HbF) being present showed reduction in disease severity, owing to which hydroxyurea has gained significant recognition. The latter’s exact mechanism of action is yet unknown, but it has been demonstrated that the resulting rise in HbF raises hemoglobin levels and lessens the incidence of acute chest syndrome and vaso-occlusive crises. In the United Arab Emirates, our study is the first to assess the effects of hydroxyurea therapy in pediatric SCD patients. Methods: We conducted a retrospective cross-sectional study on 100 patients aged 2–13 years who were diagnosed with SCD, under regular outpatient follow-up with pediatric hematology clinic and receiving hydroxyurea therapy for at least 2 years. Basic hematologic parameters, frequency of SCD complications, and need for blood transfusions were studied. Results: Our analysis has shown a statistically significant (p < 0.05) correlation between hydroxyurea therapy and improved baseline hemoglobin and HbF levels; it decreased the incidence of painful crises and acute chest syndrome episodes; reduced the demand for blood transfusions; and recorded no side effects (pancytopenia or liver function disturbance). Conclusions: This study is the first of its kind in the UAE, and our findings support those of international data. The use of hydroxyurea therapy in SCD significantly improved hematologic and clinical parameters, thus markedly improving the patient’s quality of life. The side-effect profile is also limited, which further supports the fact that hydroxyurea is a relatively safe drug.

Most adults with severe HbSC disease are not treated with hydroxyurea.

Sickle cell hemoglobin SC (HbSC) disease is the second most frequent sickle cell disease (SCD) genotype after sickle cell anemia (HbSS). Globally, ∼55 000 newborns with HbSC are delivered annually, with the highest HbC gene frequency in West Africa. In Ghana, 40% of adults visiting the Ghana Institute of Clinical Genetics SCD clinic have HbSC. Unlike HbSS, hydroxyurea use is not routinely recommended for individuals with HbSC because of the perceived high-risk to benefit ratio. To test the hypothesis that at least 5% of adults with HbSC will meet the American Society of Hematology criteria for severe disease, we conducted a retrospective descriptive cohort study of all individuals with HbSC (≥18 years) who visited the clinic in 2019. Adults with HbSC aged from 18 to 45 years were selected. We identified a comparison group of 639 individuals with HbSS and matched the frequency based on the age and sex of individuals with HbSC. Severe disease was defined as a history of ≥3 SCD-associated moderate or severe pain episodes per year, history of acute chest syndrome, and severe symptomatic chronic anemia that interferes with daily activities or quality of life. The study end points were the proportion of individuals with SCD who met the definition of severe disease and were eligible for hydroxyurea. In total, 64 of 639 (10.0%) individuals with HbSC met the eligibility criteria for hydroxyurea therapy compared with 154 of 639 (24.1%) individuals with HbSS. Less than 1% and 3% of individuals with severe HbSC and HbSS, respectively, were routinely prescribed with hydroxyurea in this tertiary care medical center.

The APC-EPCR-PAR1 axis in sickle cell disease.

Sickle Cell Disease (SCD) is a group of inherited hemoglobinopathies. Sickle cell anemia (SCA) is caused by a homozygous mutation in the β-globin generating sickle hemoglobin (HbS). Deoxygenation leads to pathologic polymerization of HbS and sickling of erythrocytes. The two predominant pathologies of SCD are hemolytic anemia and vaso-occlusive episodes (VOE), along with sequelae of complications including acute chest syndrome, hepatopathy, nephropathy, pulmonary hypertension, venous thromboembolism, and stroke. SCD is associated with endothelial activation due to the release of danger-associated molecular patterns (DAMPs) such as heme, recurrent ischemia-reperfusion injury, and chronic thrombin generation and inflammation. Endothelial cell activation is mediated, in part, by thrombin-dependent activation of protease-activated receptor 1 (PAR1), a G protein coupled receptor that plays a role in platelet activation, endothelial permeability, inflammation, and cytotoxicity. PAR1 can also be activated by activated protein C (APC), which promotes endothelial barrier protection and cytoprotective signaling. Notably, the APC system is dysregulated in SCD. This mini-review will discuss activation of PAR1 by APC and thrombin, the APC-EPCR-PAR1 axis, and their potential roles in SCD.

Acute Chest Syndrome in Sickle Cell Disease.

Acute chest syndrome (ACS) is the leading cause of mortality among individuals with sickle cell disease (SCD) accounting for 25% of all deaths. The etiologies and clinical manifestations of ACS are variable among children and adults, with a lack of clear risk stratification guidelines for the practicing clinician. In addition, the management of ACS is based on limited evidence and is currently guided primarily by expert opinion. This manuscript reviews the pathophysiology, risk factors, and current management strategies for ACS through a review of published data on this subject between 1988 and 2022. Blood transfusion is often used as a therapeutic intervention for ACS to increase blood's oxygen-carrying capacity and reduce complications by reducing hemoglobin S (HbS) percentage, based on the very low quality of the evidence about its efficacy. The benefit of RBC transfusion for ACS has been described in case series and observational studies, but randomized studies comparing simple transfusion vs. exchange transfusions for ACS are lacking. In this review, we conclude that the development of clinical and laboratory risk stratification is necessary to further study an optimal management strategy for individuals with ACS to avoid transfusion-related complications while minimizing mortality.

Plasma exchange-A useful adjunct therapy to red cell exchange in patients with sickle cell disease and multiorgan dysfunction.

Urgent red cell exchange (RBCx) is indicated for many complications of sickle cell disease (SCD), including acute chest syndrome, stroke, and hepatic/splenic sequestration. Many who receive RBCx remain hospitalized and develop further complications, including multiple organ dysfunction syndrome (MODS), a leading cause of death in intensive care units. Therapeutic plasma exchange (TPE) has been advocated as an effective treatment of MODS, but its role in SCD compared with RBCx alone is not well studied. We identified all ICU encounters from 2013 to 2019 involving RBCx procedures for MODS or SCD crisis that progressed to MODS, a total of 12 encounters. Data regarding hospital length of stay (LOS), survival, number of TPE procedures following RBCx, and procedure characteristics were collected. Surrogate laboratory markers of end-organ damage and disease severity scores were recorded at the time of admission, post-RBCx, post-TPE, and at discharge. Eight encounters involved RBCx followed by TPE (TPE group) while four involved RBCx alone (RBCx group). The TPE group had a higher SOFA score at ICU admission (9.5 vs. 7.0), greater predicted mortality, and a statistical trend toward higher disease severity scores following RBCx relative to the RBCx group (p = 0.10). The TPE group showed a significantly greater decrease in SOFA score between RBCx and discharge (p = 0.04). No significant difference in mortality or hospital LOS was observed between the groups. The findings suggest TPE may be considered as an adjunct treatment for patients with acute complications of SCD that progress to MODS, especially in cases where there is no significant improvement following RBCx.

Role of social disparity in 30-day readmissions and healthcare utilization in patients with history of sickle cell crisis in United States: Cross-sectional analysis from US national database.

e18666 Background: Factors like age, mental status, spirituality, financial security, and clinic attendance affect hospital admissions/readmissions in sickle cell disease patients. To further understand the predisposing factors associated with increased readmissions in sickle cell disease patients, this study examined the relationship between readmission rates and socioeconomic status of Sickle cell patients in the US. Methods: All adult hospitalized patients in the Nationwide Readmission Database (NRD) for the year 2019 were captured. The sample population included all patients with primary diagnosis of Sickle cell crisis, identified using ICD-10 codes (International Classification of Diseases, tenth edition). We used the Wilcoxon rank sum test to compare continuous variables and chi square test for categorical variables. Predictors of readmission were analyzed using multivariate logistic regression models. We used StataCorp LLC MP4 17 version to perform statistical analysis. Results: The sample size included 48,715 patients admitted with sickle cell crisis, of which 55.12% were females and 44.88% were males. The mean age of presentation was 32.84 years. The rate of all cause 30-day readmission in patients admitted with Sickle cell crisis was 27.19%. The total hospital charges for these readmitted patients during the year 2019 was 507 million dollars and total length of stay was 69,418 days (about 190 years). The most common causes of readmissions were Sickle cell crisis including Acute chest syndrome and splenic sequestration crisis, followed by sepsis due to MRSA and femoral fractures. After adjusting for confounders on multivariate analysis, compared to patients belonging to income category 1 ( &lt; $46,000), patients in category 2 ($46,000-$58,999) had 11% lower risk (p-value 0.018) and category 3 had 16% lower risk (p-value 0.008) of 30-day readmission. However, there was no increased risk of death based on socioeconomic status (OR 1.03, p-value 0.875). Conclusions: Our study concludes that socioeconomically deprived Sickle cell crisis patients are at higher risk of readmissions. Factors like poor living situation, lack of means for transportation, potential lower level of education leading to decreased medication compliance and clinic follow ups could be attributed to these findings. Interventions targeting this population can help reduce healthcare burden and patient morbidity significantly. [Table: see text]

Barriers to medication adherence in sickle cell disease: A comprehensive theory-based evaluation using the COM-B model.

Sickle cell disease (SCD) affects more than 100,000 Americans, with complications such as pain episodes and acute chest syndrome. Despite the efficacy of hydroxyurea in reducing these complications, adherence remains low. Study objectives were to examine barriers to hydroxyurea adherence, and to evaluate the relationship between barriers and their impact on adherence. In this cross-sectional study, patients with SCD and their caregivers were enrolled if they were taking hydroxyurea. Study measures included demographics, self-report of adherence using visual analog scale (VAS), and the Disease Management and Barriers Interview (DMI)-SCD. The DMI-SCD was mapped to the Capability, Opportunity, Motivation, and Behavior (COM-B) model. Forty-eight caregivers (females 83%, median age 38 [34-43]) and 19 patients (male 53%, median age 15 [13.5-18]) participated. Using VAS, many patients (63%) reported low hydroxyurea adherence, while most caregivers (75%) reported high adherence. Caregivers endorsed barriers across multiple COM-B components, with physical opportunity (e.g., cost) and reflective motivation (e.g., SCD perceptions) being the most identified categories (48% and 42%), respectively. Patients' most identified barriers included psychological capability (e.g., forgetfulness) and reflective motivation (84% and 68%), respectively. Patients' and caregivers' VAS scores negatively correlated with the number of barriers (rs =-.53, p=.01; rs =-.28, p=.05) and COM-B categories (rs =-.51, p=.02; rs =-.35, p=.01), respectively, suggesting lower adherence with more endorsed barriers. Fewer barriers to hydroxyurea adherence were associated with higher adherence. Understanding barriers to adherence is essential to develop tailored interventions aimed at improving adherence.